Antioxidants with Omega 3 Fatty Acids Capsules

Each soft gelatin capsule contains:

Alpha Lipoic Acid NF 50 mg

Eicosapentaenoic Acid 45 mg

Docosahexaenoic Acid 30 mg

Mixed Carotenoids - 30% oily suspension 10 mg

Zinc 7.5 mg

(as Zinc Sulphate Monohydrate IP)

Lycopene 10% 25 mg

Manganese 1.5 mg (as Manganese Sulfate Monohydrate USP)

Copper (as Cupric Sulfate USP) 1 mg

Chromium 200 mcg

(as Chromium Nicotinate) Selenium 150 mcg

(as Selenium Dioxide USP)

Excipients q.s.

Colours: Sunset Yellow FCF, Ponceau 4R Supra IH, Erythrosine Supra IH, Brilliant Blue FCF IH & Titanium Dioxide IP

Soft gelatin capsule

Alpha Lipoic Acid (50 mg), Eicosapentaenoic Acid (45 mg), Docosahexaenoic Acid (30 mg), Mixed Carotenoids (10 mg), Zinc (7.5 mg), Lycopene (25 mg), Manganese (1.5 mg), Copper (1 mg), Chromium (200 mcg), Selenium (150 mcg)

4.1 Therapeutic indication

Antioxidants with Omega 3 Fatty Acids capsules for nutritional supplements in cardiovascular diseases and diabetes.

4.2 Posology and method of administration

Adults and the Elderly: One capsule daily, preferably taken after meals. Capsules should be swallowed whole & not to be opened, chewed, or crushed.

4.3 Contraindications

Patients with hypersensitivity reactions to any of its components.

4.4 Special warnings and precautions for use

Whilst taking Bevon-CD Capsules both protein and energy are also required to provide complete nutrition in the daily diet.

Other vitamins, minerals or supplements should be taken with this preparation only under medical supervision.

Do not take Bevon-CD Capsules on an empty stomach. Do not exceed the stated dose. Keep out of the reach of children. If symptoms persist, consult your doctor.

4.5 Drugs interactions

Copper: Zinc may inhibit the absorption of copper.

Tetracycline Antibacterials:

Zinc may reduce the absorption of concurrently administered tetracyclines, also the absorption of zinc may be reduced by tetracyclines; when both are being given an interval of at least three hours should be allowed.

Quinolone Antibacterials:

Zinc may reduce the absorption of quinolones; ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin and ofloxacin.

Calcium Salts: The absorption of zinc may be reduced by calcium salts.

Iron: The absorption of zinc may be reduced by oral iron, also the absorption of oral iron may be reduced by zinc.

4.6 Use in special populations

Children under 12 years of age

Bevon-CD Capsules are not recommended for this age group.

Pregnancy and lactation

Bevon-CD Capsules may be administered during pregnancy and lactation at the recommendation of the physician.

4.7 Effects on ability to drive and use machines

None anticipated. Bevon-CD has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

There are no special recommendations. Administer symptomatic treatment.

5.1 Pharmacodynamic properties

Alpha-lipoic acid (ALA)

It is a potent antioxidant naturally produced in the body and found in foods like spinach, broccoli, and potatoes. It plays a crucial role in energy metabolism and helps regenerate other antioxidants, such as vitamins C and E.

ALA helps neutralize free radicals, reducing oxidative stress and inflammation, which are key factors in cardiovascular diseases. It can improve the function of the endothelium (the inner lining of blood vessels), which is essential for maintaining vascular health. Studies suggest that ALA can help prevent the progression of atherosclerosis, a condition characterized by the build-up of plaques in the arteries.

ALA has been shown to improve insulin sensitivity, which helps in better glucose uptake by cells, thereby lowering blood sugar levels. It can alleviate symptoms of diabetic neuropathy, such as pain and numbness, by reducing oxidative stress and improving nerve function. ALA may help protect against various complications of diabetes, including cardiovascular issues and kidney damage.

Omega-3 fatty acids (Eicosapentaenoic Acid and Docosahexaenoic Acid)

Omega-3 fatty acids (ω-3 FA) may help reduce the risk of cardiovascular disease (CVD) in patients with diabetes.

Omega-3 fatty acids, especially EPA and DHA, are known to lower triglyceride levels, which can reduce the risk of heart disease. They help reduce inflammation, a key factor in the development of atherosclerosis. Regular consumption of omega-3s is associated with a lower risk of myocardial infarction, strokes, and other cardiovascular events.

Omega-3 fatty acids may improve insulin sensitivity, helping to manage blood sugar levels. Reduces Inflammation: Chronic inflammation is a common issue in diabetes, and omega-3s can help mitigate this.

Mixed Carotenoids

Carotenoids are naturally occurring pigments found in many fruits and vegetables, giving them their vibrant colors. They are powerful antioxidants and play a significant role in human health.

Carotenoids include compounds like beta-carotene, lycopene, lutein, and zeaxanthin. These pigments are found in high concentrations in foods such as carrots, tomatoes, spinach, and kale (leaf cabbage). Carotenoids help reduce oxidative stress, which is a major factor in the development of cardiovascular diseases. They support the health of the endothelium, the inner lining of blood vessels, which is crucial for maintaining vascular health.

Carotenoids have anti-inflammatory effects that can help prevent atherosclerosis, the build-up of plaques in the arteries. Carotenoids can help reduce blood sugar levels and improve insulin sensitivity, which is beneficial for managing diabetes. Higher dietary intake of carotenoids, particularly beta-carotene, has been linked to a lower risk of developing type 2 diabetes. By reducing oxidative stress and inflammation, carotenoids can help protect against complications associated with diabetes.

Zinc

Zinc is an essential mineral that plays a crucial role in various bodily functions, including immune response, protein synthesis, and cell division. Its importance extends to cardiovascular health and diabetes management.

Zinc helps reduce oxidative stress, which is a significant factor in the development of cardiovascular diseases. It supports the proper functioning of the antioxidant system, helping to protect the heart and blood vessels. Zinc can suppress inflammatory mediators, reducing inflammation that contributes to atherosclerosis. Adequate zinc levels are essential for maintaining endothelial function, which is crucial for vascular health.

Zinc is involved in the formation, storage, and release of insulin, making it vital for blood glucose regulation. It acts as a cofactor for enzymes that are crucial in insulin signaling pathways. Zinc helps mitigate oxidative stress and inflammation, both of which are common in diabetes and its complications. Adequate zinc levels can reduce the risk of developing complications associated with diabetes, such as cardiovascular issues and neuropathy.

Lycopene

Lycopene is a powerful antioxidant found in red and pink fruits and vegetables, such as tomatoes, watermelon, and pink grapefruit. It is a type of carotenoid, which gives these foods their vibrant color.

Lycopene helps neutralize free radicals, reducing oxidative stress and inflammation, which are key factors in the development of cardiovascular diseases. It supports the health of the endothelium, the inner lining of blood vessels, which is crucial for maintaining vascular health. Higher blood levels of lycopene have been associated with a significantly lower risk of stroke.

Lycopene helps mitigate oxidative stress, which is a common issue in diabetes and its complications. Some studies suggest that lycopene can improve insulin sensitivity, helping to manage blood sugar levels more effectively. By reducing inflammation and oxidative stress, lycopene can help protect against complications associated with diabetes, such as cardiovascular issues.

Manganese

Manganese is an essential trace mineral that plays a significant role in various bodily functions, including enzyme activation, bone formation, and glucose metabolism. Its importance extends to cardiovascular health and diabetes management.

Manganese is a component of the antioxidant enzyme superoxide dismutase (SOD), which helps protect cells from oxidative damage. This is crucial in preventing cardiovascular diseases. By reducing inflammation, manganese can help prevent the development of atherosclerosis. Adequate manganese levels are associated with better regulation of blood pressure, which is vital for cardiovascular health.

Glucose Metabolism: Manganese is involved in the metabolism of carbohydrates and the regulation of blood sugar levels. It helps in the synthesis and secretion of insulin, which is crucial for glucose homeostasis. Low levels of manganese can impair insulin secretion and increase insulin resistance, while adequate manganese intake can improve insulin sensitivity and glucose metabolism. Manganese helps reduce oxidative stress and inflammation, which are common issues in diabetes and its complications.

Copper

Copper is an essential trace mineral that plays a significant role in various physiological processes, including cardiovascular health and diabetes management.

Copper is a component of several antioxidant enzymes, such as superoxide dismutase (SOD), which help protect cells from oxidative damage. This is crucial in preventing cardiovascular diseases. Copper helps reduce inflammation, which can prevent the development of atherosclerosis. Adequate copper levels are essential for maintaining proper heart function. Copper deficiency can lead to heart issues such as cardiac hypertrophy and heart failure.

Copper is involved in the metabolism of insulin, which is crucial for blood glucose regulation. It helps in the proper functioning of enzymes that are important for insulin signaling. Copper helps mitigate oxidative stress and inflammation, both of which are common in diabetes and its complications.

Chromium

Chromium is an essential trace mineral that plays a vital role in various bodily functions, particularly in the metabolism of carbohydrates, fats, and proteins. It is often found in foods like whole grains, nuts, broccoli, and meat.

Chromium supplementation has been shown to improve lipid profiles by reducing total cholesterol and triglycerides, which are risk factors for cardiovascular diseases. Chromium helps reduce inflammation, which is a key factor in the development of atherosclerosis. Some studies suggest that chromium can help regulate blood pressure, contributing to overall cardiovascular health.

Chromium is known to enhance insulin sensitivity, which helps in better glucose uptake by cells, thereby lowering blood sugar levels. Supplementation with chromium has been shown to improve glycemic control in people with type 2 diabetes by reducing fasting blood glucose and insulin levels. Chromium helps mitigate oxidative stress, which is common in diabetes and its complications.

Selenium

Selenium is an essential trace mineral that plays a crucial role in various bodily functions, including antioxidant defense, thyroid hormone metabolism, and immune function. It is found in foods like nuts, seafood, and whole grains.

Selenium is a component of antioxidant enzymes like glutathione peroxidase, which help protect cells from oxidative damage. This is important in preventing cardiovascular diseases. Selenium helps reduce inflammation, which can prevent the development of atherosclerosis.

Adequate selenium levels are associated with a lower risk of heart disease. Selenium deficiency has been linked to an increased risk of cardiovascular issues.

Selenium may improve insulin sensitivity, helping to regulate blood sugar levels more effectively. By mitigating oxidative stress, selenium can help protect against complications associated with diabetes, such as cardiovascular problems. While selenium has benefits, excessive intake can lead to toxicity and may increase the risk of type 2 diabetes. It’s important to maintain a balanced intake.

5.3 Pharmacokinetic properties

Zinc Sulfate (Zinc): Zinc is poorly absorbed from the gastro-intestinal tract. It is widely distributed throughout the body. It is excreted in the faeces with traces appearing in the urine.

Manganese Sulfate (Manganese): Manganese salts are poorly absorbed.

Copper Sulfate (Copper): Copper is absorbed from the gastro-intestinal tract and its major route of excretion is in the bile.

Selenium: Although it has been established that selenium is essential to human life, very little information is available on its function and metabolism.

Chromium Nicotinate

Most chromium compounds are soluble at the pH of the stomach, but less soluble hydroxides may form as pH is increased. The environment of the gastrointestinal tract and ligands provided by foods and supplements are important for mineral absorption.

Mixed Carotenoids

Carotenoids are fat-soluble compounds, meaning they are absorbed more efficiently when consumed with dietary fats. They are absorbed in the small intestine through passive diffusion and are incorporated into chylomicrons, which are lipoprotein particles that transport dietary lipids. Once absorbed, carotenoids are transported via the lymphatic system into the bloodstream. Carotenoids undergo metabolic conversion in the liver. Carotenoids and their metabolites are primarily excreted through bile and feces. A small amount may also be excreted through urine.

Alpha Lipoic Acid (ALA)

ALA is absorbed in the small intestine. Its oral bioavailability is relatively low, around 30%, due to its instability in the stomach and rapid hepatic degradation. Once absorbed, ALA is distributed throughout the body and can cross the blood-brain barrier. It is converted to its reduced form, dihydrolipoic acid (DHLA), in various tissues. ALA undergoes extensive metabolism in the liver. It is reduced to DHLA, which has potent antioxidant properties. Both ALA and DHLA can regenerate other antioxidants like vitamins C and E. ALA and its metabolites are primarily excreted through the kidneys. The compound has a relatively short half-life, which limits its duration of action.

Lycopene

Lycopene absorption occurs via passive diffusion or facilitated by scavenger receptor class B type 1 (SR-B1) in enterocytes, potentially alongside other carotenoids. Partial cleavage by enzymes like Beta-Carotene Oxygenase 1 (BCO1) and Beta-Carotene Oxygenase 2 (BCO2) in enterocytes may occur. Transport involves packaging into chylomicrons, then release into the lymph and portal circulation. Lycopene primarily associates with LDL and is distributed to various organs, notably accumulating in the liver but also present in adipose tissue, adrenal glands, testes, ovaries, kidneys, lungs, skin, and the prostate. Lycopene and its metabolites are primarily eliminated from the body through fecal excretion, a smaller portion may be excreted via urine.

6.1 Animal Toxicology or Pharmacology

Not available

Bevon -CD Capsules contains Antioxidants with Omega 3 Fatty Acids.

Alpha Lipoic Acid (50 mg): An antioxidant that helps protect cells from damage and supports energy production in the body.

Eicosapentaenoic Acid (EPA, 45 mg): An Omega-3 fatty acid that supports heart health, reduces inflammation, and may improve mental health.

Docosahexaenoic Acid (DHA, 30 mg): Another Omega-3 fatty acid crucial for brain and eye health, as well as reducing inflammation.

Mixed Carotenoids (10 mg): These are antioxidants that can help protect your cells from damage and support eye health.

Zinc (7.5 mg): An essential mineral that supports immune function, wound healing, and DNA synthesis.

Lycopene (25 mg): An antioxidant found in tomatoes and other red fruits and vegetables, known for its potential to reduce the risk of certain cancers and support heart health.

Manganese (1.5 mg): A mineral important for bone formation, blood clotting, and reducing inflammation.

Copper (1 mg): Essential for iron metabolism, energy production, and maintaining healthy connective tissues.

Chromium (200 mcg): Helps regulate blood sugar levels by enhancing the action of insulin.

Selenium (150 mcg): An antioxidant that plays a role in DNA synthesis, thyroid function, and protecting the body from oxidative damage and infection.

These ingredients work together to provide a range of health benefits, from supporting heart and boosting your immune system and protecting your cells from damage.

8.1 Incompatibilities

Not Applicable

8.2 Shelf-life

Refer on pack

8.3 Packaging information

10 Blister strips of 10 Capsules each

8.4 Storage and handing instructions

Store in a dry place below 25°C.

Protected from direct sunlight.

Keep out of reach of children.

The capsule should be swallowed whole and not be opened, chewed, or crushed.

10th October 2024

Multivitamin, Multimineral & Antioxidant Suspension

Each 5 ml contains :

• Cholecalciferol IP (As stabilized) 200 IU
• Pyridoxine Hydrochloride IP 1 mg
• Niacinamide IP 15 mg
• Cyanocobalamin IP 1 mcg
• Zinc Sulphate Monohydrate IP
• Equivalent to elemental Zinc 3 mg
• Betacarotene dispersion 2.5% 38 mg
• Manganese Sulfate Monohydrate USP
• Equivalent to elemental Manganese 0.8 mg
• Sodium Molybdate Dihydrate BP
• Equivalent to elemental Molybdenum 8 mcg
• Sodium Selenite Pentahydrate BP
• Equivalent to elemental Selenium 10 mcg
• L-Lysine Hydrochloride USP 30 mg
• Potassium Iodide IP
• Equivalent to elemental Iodine 50 mcg
• Biotin USP 10 mcg
• Chromium Picolinate USP
• Equivalent to elemental Chromium 10 mcg
• Myo-Inositol IP 10 mg
• Excipients q.s.
• Colour : Quinoline Yellow FCF
• In a flavoured syrupy base
• Appropriate overages of vitamins added.

Oral suspension

4.1 Therapeutic indication

For vitamin and mineral deficiency states in adults and children.

4.2 Posology and method of administration

One teaspoonful (5 ml) to be taken once daily.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in the formulation.

4.4 Special warnings and precautions for use

• Whilst taking Bevon Suspension both protein and energy are also required to provide complete nutrition in the daily diet. No other vitamins, minerals or supplements with or without vitamin A should be taken with this preparation except under medical supervision.
• Do not take Bevon Suspension on an empty stomach. Do not exceed the stated dose. Keep out of the reach of children. If symptoms persist, consult your doctor
• Evidence from Randomised Control Trials suggests that high doses (20-30 mg/day) β-carotene intake may increase the risk of lung cancer in current smokers and those previously exposed to asbestos. This high-risk population should consider the potential risks and benefits of Bevon Suspension, which contain 5mg of β-carotene per recommended daily dose, before use.

4.5 Drugs interactions

Zinc sulphate reduce the absorption of tetracyclines.

4.6 Use in special populations

Pregnancy and breastfeeding

Bevon suspension may be administered during pregnancy and lactation at the recommendation of the physician.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Immune system disorders : Hypersensitivity reaction (such as rash) Gastrointestinal disorders : Gastrointestinal disturbances (such as nausea, vomiting and abdominal pain).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via

email to : medico@zuventus.com

By reporting side effects, you can help provide more information on the safety of this medicine.

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

No cases of overdosage due to Bevon therapy have been reported. In case of accidental overdose, discontinue use and seek professional assistance immediately. Any symptoms which may be observed due to the ingestion of large quantities of suspension will be due to the fat soluble vitamin content. Gastric lavage may be necessary to remove drug already released into the stomach. Signs and symptoms such as gastrointestinal disorders like diarrhoea may be associated with an overdose of Bevon.

5.1 Pharmacodynamic properties / Mechanism of action

Cholecalciferol

Vitamin D is required for the absorption of calcium and phosphate from the gastro-intestinal tract and for their transport. Its involvement in the control of calcium metabolism and hence the normal calcification of bones is well documented. Deficiency of Vitamin D in children may result in the development of rickets.

Pyridoxine hydrochloride

The active coenzyme form of vitamin B6 (Pyridoxine) is pyridoxal 5 ′-phosphate. Approximately 80% of the body's total vitamin B6 is present as pyridoxal phosphate in muscle. Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism. It is also the co-factor for glycogen phosphorylase, where the phosphate group is catalytically important. Vitamin B6 helps the body to make several neurotransmitters. It is needed for normal brain development and function, and helps the body to make the hormones serotonin and norepinephrine, which influence mood, and melatonin, which helps to regulate the body clock. Along with vitamins B12 and B9 (folic acid), B6 helps to control levels of homocysteine in the blood. In addition, vitamin B6 is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin B6 deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol and vitamin D.

Niacinamide

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin; its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions. Nicotinamide has important role in DNA repair mechanism.

Cyanocobalamin

Vitamin B12 is found only in foods of animal origin. Vitamin B12 is essential for cellular DNA synthesis and hence contributes to functions of various tissues of the body, formation of myelin sheath, more so the rapidly dividing and proliferating cellular systems such as blood and gastric epithelium. The absorbed inert form of cyanocobalamin is converted into two important active forms. One is methylcobalamininvolved in maturation of red blood corpuscles. The second active form is adenosylcobalamin involved in healthy myelination and neuronal integrity. Methylcobalamin deficiency leads to folate trap resulting in megaloblastic anemia. Deficiency of adenosylcobalamin leads to accumulation of large amount of methylmalonyl-CoA resulting in synthesis and incorporation of nonphysiological fatty acids into neuronal lipids, causing, demyelination, axonal degeneration and neuronal death leading to neurological complications.

Zinc sulfate

Zinc is an essential trace mineral necessary for the proper function of about 300 different enzymes. Therefore, zinc plays a role in virtually all biochemical pathways and physiological processes in the body. Thirty percent of the body's zinc is stored in the bones and 60% in muscles. The other 10% is found in virtually all body tissues. Zinc is important for wound healing, immune system support and to increase fertility (sperm production). It also assists digestion, energy production, growth, cellular repair, collagen synthesis, bone strength, cognitive function, and carbohydrate metabolism (glucose utilization and insulin production). Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti- inflammatory agent. Mild zinc deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiency, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more.

Beta carotene

β-carotene is the most prominent and efficient member of the group of carotenoids (natural colorants that occur in the human diet). Carotenoids are red, orange, or yellow, fat-soluble compounds. Alpha, beta, and gamma carotene are considered provitamins because they can be converted to active vitamin A. Beta-carotene is converted to retinol, which is essential for vision and growth. ROS-induced oxidative stress is suggested as being basic to several human diseases. β-carotene has a unique type of antioxidant activity. Beta carotene traps free radicals and studies suggest that it may also reduce tumor development. Studies have shown that vitamin A is essential to the normal growth of epithelial tissues

Manganese sulfate

Manganese is an essential element for humans and is required for growth, development, and maintenance of health. Manganese is necessary for a variety of metabolic functions including those involved in skeletal system development, energy metabolism, activation of certain enzymes, nervous system function, immunological system function, and reproductive hormone function. It is an antioxidant that protects cells from damage due to free radicals. Manganese also plays an essential role in regulation of cellular energy, bone and connective tissue growth and blood clotting. In the brain, Manganese is an important cofactor for a variety of enzymes, including the antioxidant enzyme superoxide dismutase, as well as enzymes involved in neurotransmitter synthesis and metabolism.

Sodium molybdate dihydrate

Molybdenum belongs to a group of essential microelements. Molybdenum-containing enzymes catalyze basic metabolic reactions in the nitrogen, sulfur, and carbon cycles and are important for variety of metabolic pathways.

Sodium selenite

Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant, immune functions and anti-inflammatory effects to the production of active thyroid hormone. Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline. Selenium supplementation has antiviral effects, is essential for male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of various cancers

L-Lysine

L-Lysine is classified as an essential amino acid. Lysine helps in synthesis of connective tissues such as bone, skin, collagen, and elastin; synthesis of carnitine and resultant conversion of fatty acids to energy; support for healthy growth and development in children; and maintenance of healthy immune function, particularly with regard to antiviral activity.

Iodine (Potassium iodide)

Iodine is an essential constituent of the thyroid hormones.

Biotin

Biotin (Vitamin B7 or H) is a water soluble B vitamin that is essential for bodily health. It helps the body to process fat and sugars, and it helps form a critical process in fat production in the body. Biotin is involved in a number of carboxylase reactions. Biotin is often recommended as a dietary supplement for healthy skin, hair and nails. Biotin deficiency is characterized by development of a fine scaly dermatitis, hair loss, conjunctivitis, ataxia and delayed development.

Chromium picolinate

Chromium is a critical cofactor in the action of insulin. Results from some trials have indicated that chromium supplementation increases muscle gain and fat loss associated with exercise and improves glucose metabolism and the serum lipid profile in patients with or without diabetes. Low chromium levels can increase blood sugar, triglycerides, cholesterol levels, and increase the risk for a number of conditions, such as diabetes and heart disease.

Myo-Inositol

Inositol is an essential molecule found ubiquitously in biological systems. Inositol 1,4,5-triphosphate plays an essential role as a secondary messenger in the InsP3/Ca+2 signal transduction pathway, which is responsible for modulating the activity of numerous cellular processes. Biochemical functions elucidated for phosphatidyl inositol in biological membranes include the mediation of cellular responses to external stimuli, nerve transmission, and the regulation of enzyme activity through specific interactions with various proteins.

5.2 Pharmacokinetic properties

Cholecalciferol

Cholecalciferol is absorbed from the gastro-intestinal tract into the circulation. In the liver, it is hydroxylated to 25-hydroxycholecalciferol, is subject to entero-hepatic circulation and is further hydroxylated to 1,25-dihydroxycholecalciferol in the renal tubule cells. Vitamin D metabolites are bound to specific plasma proteins.

Pyridoxine hydrochloride

Pyridoxine is absorbed from the gastro-intestinal tract and converted to the active pyridoxal phosphate which is bound to plasma proteins. It is excreted in the urine as 4-pyridoxic acid.

Niacinamide

Nicotinic acid is absorbed from the gastro-intestinal tract, is widely distributed in the body tissues and has a short half-life.

Cyanocobalamin

Cyanocobalamin is absorbed from the gastro-intestinal tract and is extensively bound to specific plasma proteins. A study with labelled Vitamin B12 showed it was quickly taken up by the intestinal mucosa and held there for 2 - 3 hours. Peak concentrations in the blood and tissues did not occur until 8 - 12 hours after dosage with maximum concentrations in the liver within 24 hours. Cobalamins are stored in the liver, excreted in the bile and undergo enterohepatic recycling. Part of a dose is excreted in the urine, most of it in the first eight hours.

Zinc sulfate

Zinc is poorly absorbed from the gastro-intestinal tract. It is widely distributed throughout the body. It is excreted in the faeces with traces appearing in the urine.

Beta carotene

Except when liver function is impaired, Vitamin A is readily absorbed. β-carotene (as in Bevon Suspension) is Provitamin A and is the biological precursor to Vitamin A. It is converted to Vitamin A (Retinol) in the liver; retinol is emulsified by bile salts and phospholipids and absorbed in a micellar form. Part is conjugated with glucuronic acid in the kidney and part is metabolised in the liver and kidney, leaving 30 to 50% of the dose for storage in the liver. It is bound to a globulin in the blood. Metabolites of Vitamin A are excreted in the faeces and the urine.

Manganese sulfate

Manganese salts are poorly absorbed.

Sodium molybdate dihydrate

In humans, molybdenum is known to function as a cofactor for four enzymes : Sulfite oxidase catalyzes the transformation of sulfite to sulfate, a reaction that is necessary for the metabolism of sulfur-containing amino acids (methionine and cysteine).

Sodium selenite

Although it has been established that selenium is essential to human life, very little information is available on its function and metabolism

L-Lysine

L-Lysine absorbed from the lumen of the small intestine into the enterocytes by an active transport process.

Potassium iodide

Potassium salts are absorbed from the gastro-intestinal tract. Potassium is excreted in the urine, the faeces and in perspiration. Urinary excretion of potassium continues even when intake is low.

Biotin

Following absorption, biotin is stored in the liver, kidney and pancreas.

Chromium picolinate

Most chromium compounds are soluble at the pH of the stomach, but less soluble hydroxides may form as pH is increased. The environment of the gastrointestinal tract and ligands provided by foods and supplements are important for mineral absorption.

Myo-Inositol

Oral ingestion of inositol is registered to generate a maximal plasma concentration of 36 - 45 mcg. The pharmacokinetic profile of inositol was studied in preterm infants and the estimated volume of distribution was reported to be 0.5115 L/kg. It is thought that inositol can be found bound to plasma proteins.

6.1 Animal toxicology or pharmacology

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the prescribing information.

Bevon suspension contain a comprehensive formula of vitamins, minerals and antioxidants specially designed to support health and wellbeing in adults by unlocking energy and strengthening immunity. Most vitamins, minerals and trace elements are not produced by human body and hence are dependent on dietary supply of these nutrients. Since vitamins, minerals and trace elements are involved in many metabolic processes in the body, an adequate supply of these vital substances contribute to physical and mental well being.

8.1 Incompatibilities

No major incompatibilities are known

8.2 Shelf-life

18 Months

8.3 Packaging information

A bottle of 200 ml.

8.4 Storage and handing instructions

Store protected from light at a temperature not exceeding 25°C.

Do not freeze.

Keep out of reach of children.

SHAKE WELL BEFORE USE.

Do not take Bevon Suspension :

• if you are allergic (hypersensitive) to any of the ingredients of Bevon suspension.
• if you suffer from hypercalcaemia (high level of calcium in the blood)

Take special care with Bevon Suspension

Before you are given Bevon Suspension tell your doctor, dietician or pharmacist if :

• you are pregnant or thinking of becoming pregnant
• you are a smoker
• you have an asbestos related illness such as asbestosis
• you suffer from thyroid problems.

If any of the above applies to you, or if you are not sure, speak to your doctor or pharmacist before taking Bevon Suspension.

Taking other medicines

Tell your doctor if you are taking or have recently taken/used any of the following medicines as they may interfere with Bevon suspension :

• Phenytoin (used to treat epilepsy)
• Tetracycline antibiotics (used to treat infections) such as doxycycline and minocycline.

Please tell your doctor if you are taking or have recently taken/used any other medicines including other vitamin or mineral products medicines obtained without a prescription.

20.04.2022

Multivitamin & Multimineral Drops

Each ml contains :

• Cholecalciferol IP (As stabilized) 200 IU
• Pyridoxine Hydrochloride IP 0.5 mg
• Niacinamide IP 5 mg
• Cyanocobalamin IP 1 mcg
• Zinc Sulphate Monohydrate IP
• Equivalent to elemental Zinc 2 mg
• Betacarotene dispersion 2.5% 18 mg
• Manganese Sulfate Monohydrate USP
• Equivalent to elemental Manganese 3 mcg
• Sodium Molybdate Dihydrate BP
• Equivalent to elemental Molybdenum 1 mcg
• Sodium Selenite Pentahydrate BP
• Equivalent to elemental Selenium 10 mcg
• L-Lysine Hydrochloride USP 30 mg
• Potassium Iodide IP
• Equivalent to elemental Iodine 20 mcg
• Biotin USP 5 mcg
• Chromium Picolinate USP
• Equivalent to elemental Chromium 1 mcg
• Myo-Inositol IP 10 mg
• Excipients 10 mg
• Excipients q.s.
• In a flavoured syrupy base
• Appropriate overages of vitamins added.

Oral drops

4.1 Therapeutic indication

For Vitamins and Minerals deficiency state in infants and children.

4.2 Posology and method of administration

Infants : One ml (approximately 20 drops) once daily.

Children above 1 year : One ml (approximately 20 drops) twice daily.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in the formulation.

4.4 Special warnings and precautions for use

• Whilst taking Bevon Drops both protein and energy are also required to provide complete nutrition in the daily diet. No other vitamins, minerals or supplements with or without vitamin A should be taken with this preparation except under medical supervision.
• Do not take Bevon Drops on an empty stomach. Do not exceed the stated dose. Keep out of the reach of children. If symptoms persist, consult your doctor
• Evidence from Randomised Control Trials suggests that high doses (20-30 mg/day) β-carotene intake may increase the risk of lung cancer in current smokers and those previously exposed to asbestos. This high-risk population should consider the potential risks and benefits of Bevon Drops, which contain 5mg of β-carotene per recommended daily dose, before use.

4.5 Drugs interactions

Zinc sulphate reduce the absorption of tetracyclines.

4.6 Use in special populations

Pregnancy and Breastfeeding

Not indicated in this age group.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Immune system disorders : Hypersensitivity reaction (such as rash) Gastrointestinal disorders : Gastrointestinal disturbances (such as nausea, vomiting and abdominal pain).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via

email to : medico@zuventus.com

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

No cases of overdosage due to Bevon therapy have been reported. In case of accidental overdose, discontinue use and seek professional assistance immediately. Any symptoms which may be observed due to the ingestion of large quantities of drops will be due to the fat soluble vitamin content. Gastric lavage may be necessary to remove drug already released into the stomach. Signs and symptoms such as gastrointestinal disorders like diarrhoea may be associated with an overdose of Bevon.

5.1 Pharmacodynamic properties / Mechanism of action

Cholecalciferol

Vitamin D is required for the absorption of calcium and phosphate from the gastro-intestinal tract and for their transport. Its involvement in the control of calcium metabolism and hence the normal calcification of bones is well documented. Deficiency of Vitamin D in children may result in the development of rickets.

Pyridoxine hydrochloride

The active coenzyme form of vitamin B6 (Pyridoxine) is pyridoxal 5 ′-phosphate. Approximately 80% of the body's total vitamin B6 is present as pyridoxal phosphate in muscle. Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism. It is also the co-factor for glycogen phosphorylase, where the phosphate group is catalytically important. Vitamin B6 helps the body to make several neurotransmitters. It is needed for normal brain development and function, and helps the body to make the hormones serotonin and norepinephrine, which influence mood, and melatonin, which helps to regulate the body clock. Along with vitamins B12 and B9 (folic acid), B6 helps to control levels of homocysteine in the blood. In addition, vitamin B6 is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin B6 deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol and vitamin D.

Niacinamide

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin; its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions. Nicotinamide has important role in DNA repair mechanism.

Cyanocobalamin

Vitamin B12 is found only in foods of animal origin. Vitamin B12 is essential for cellular DNA synthesis and hence contributes to functions of various tissues of the body, formation of myelin sheath, more so the rapidly dividing and proliferating cellular systems such as blood and gastric epithelium. The absorbed inert form of cyanocobalamin is converted into two important active forms. One is methylcobalamininvolved in maturation of red blood corpuscles. The second active form is adenosylcobalamin involved in healthy myelination and neuronal integrity. Methylcobalamin deficiency leads to folate trap resulting in megaloblastic anemia. Deficiency of adenosylcobalamin leads to accumulation of large amount of methylmalonyl-CoA resulting in synthesis and incorporation of nonphysiological fatty acids into neuronal lipids, causing, demyelination, axonal degeneration and neuronal death leading to neurological complications.

Zinc sulfate

Zinc is an essential trace mineral necessary for the proper function of about 300 different enzymes. Therefore, zinc plays a role in virtually all biochemical pathways and physiological processes in the body. Thirty percent of the body's zinc is stored in the bones and 60% in muscles. The other 10% is found in virtually all body tissues. Zinc is important for wound healing, immune system support and to increase fertility (sperm production). It also assists digestion, energy production, growth, cellular repair, collagen synthesis, bone strength, cognitive function, and carbohydrate metabolism (glucose utilization and insulin production). Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti- inflammatory agent. Mild zinc deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiency, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more.

Beta carotene

β-carotene is the most prominent and efficient member of the group of carotenoids (natural colorants that occur in the human diet). Carotenoids are red, orange, or yellow, fat-soluble compounds. Alpha, beta, and gamma carotene are considered provitamins because they can be converted to active vitamin A. Beta-carotene is converted to retinol, which is essential for vision and growth. ROS-induced oxidative stress is suggested as being basic to several human diseases. β-carotene has a unique type of antioxidant activity. Beta carotene traps free radicals and studies suggest that it may also reduce tumor development. Studies have shown that vitamin A is essential to the normal growth of epithelial tissues.

Manganese sulfate

Manganese is an essential element for humans and is required for growth, development, and maintenance of health. Manganese is necessary for a variety of metabolic functions including those involved in skeletal system development, energy metabolism, activation of certain enzymes, nervous system function, immunological system function, and reproductive hormone function. It is an antioxidant that protects cells from damage due to free radicals. Manganese also plays an essential role in regulation of cellular energy, bone and connective tissue growth and blood clotting. In the brain, Manganese is an important cofactor for a variety of enzymes, including the antioxidant enzyme superoxide dismutase, as well as enzymes involved in neurotransmitter synthesis and metabolism.

Sodium molybdate dihydrate

Molybdenum belongs to a group of essential microelements. Molybdenum-containing enzymes catalyze basic metabolic reactions in the nitrogen, sulfur, and carbon cycles and are important for variety of metabolic pathways.

Sodium selenite

Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant, immune functions and anti-inflammatory effects to the production of active thyroid hormone. Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline. Selenium supplementation has antiviral effects, is essential for male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of various cancers

L-Lysine

L-Lysine is classified as an essential amino acid. Lysine helps in synthesis of connective tissues such as bone, skin, collagen, and elastin; synthesis of carnitine and resultant conversion of fatty acids to energy; support for healthy growth and development in children; and maintenance of healthy immune function, particularly with regard to antiviral activity.

Iodine (Potassium iodide)

Iodine is an essential constituent of the thyroid hormones.

Biotin

Biotin (Vitamin B7 or H) is a water soluble B vitamin that is essential for bodily health. It helps the body to process fat and sugars, and it helps form a critical process in fat production in the body. Biotin is involved in a number of carboxylase reactions. Biotin is often recommended as a dietary supplement for healthy skin, hair and nails. Biotin deficiency is characterized by development of a fine scaly dermatitis, hair loss, conjunctivitis, ataxia and delayed development.

Chromium picolinate

Chromium is a critical cofactor in the action of insulin. Results from some trials have indicated that chromium supplementation increases muscle gain and fat loss associated with exercise and improves glucose metabolism and the serum lipid profile in patients with or without diabetes. Low chromium levels can increase blood sugar, triglycerides, cholesterol levels, and increase the risk for a number of conditions, such as diabetes and heart disease.

Myo-Inositol

Inositol is an essential molecule found ubiquitously in biological systems. Inositol 1,4,5-triphosphate plays an essential role as a secondary messenger in the InsP3/Ca+2 signal transduction pathway, which is responsible for modulating the activity of numerous cellular processes. Biochemical functions elucidated for phosphatidyl inositol in biological membranes include the mediation of cellular responses to external stimuli, nerve transmission, and the regulation of enzyme activity through specific interactions with various proteins.

5.2 Pharmacokinetic properties

Cholecalciferol

Cholecalciferol is absorbed from the gastro-intestinal tract into the circulation. In the liver, it is hydroxylated to 25-hydroxycholecalciferol, is subject to entero-hepatic circulation and is further hydroxylated to 1,25-dihydroxycholecalciferol in the renal tubule cells. Vitamin D metabolites are bound to specific plasma proteins.

Pyridoxine hydrochloride

Pyridoxine is absorbed from the gastro-intestinal tract and converted to the active pyridoxal phosphate which is bound to plasma proteins. It is excreted in the urine as 4-pyridoxic acid.

Niacinamide

Nicotinic acid is absorbed from the gastro-intestinal tract, is widely distributed in the body tissues and has a short half-life.

Cyanocobalamin

Cyanocobalamin is absorbed from the gastro-intestinal tract and is extensively bound to specific plasma proteins. A study with labelled Vitamin B12 showed it was quickly taken up by the intestinal mucosa and held there for 2 - 3 hours. Peak concentrations in the blood and tissues did not occur until 8 - 12 hours after dosage with maximum concentrations in the liver within 24 hours. Cobalamins are stored in the liver, excreted in the bile and undergo enterohepatic recycling. Part of a dose is excreted in the urine, most of it in the first eight hours.

Zinc sulfate

Zinc is poorly absorbed from the gastro-intestinal tract. It is widely distributed throughout the body. It is excreted in the faeces with traces appearing in the urine.

Beta carotene

Except when liver function is impaired, Vitamin A is readily absorbed. β-carotene (as in Bevon Drops) is Provitamin A and is the biological precursor to Vitamin A. It is converted to Vitamin A (Retinol) in the liver; retinol is emulsified by bile salts and phospholipids and absorbed in a micellar form. Part is conjugated with glucuronic acid in the kidney and part is metabolised in the liver and kidney, leaving 30 to 50% of the dose for storage in the liver. It is bound to a globulin in the blood. Metabolites of Vitamin A are excreted in the faeces and the urine.

Manganese sulfate

Manganese salts are poorly absorbed.

Sodium molybdate dihydrate

In humans, molybdenum is known to function as a cofactor for four enzymes: Sulfite oxidase catalyzes the transformation of sulfite to sulfate, a reaction that is necessary for the metabolism of sulfur-containing amino acids (methionine and cysteine).

Sodium selenite

Although it has been established that selenium is essential to human life, very little information is available on its function and metabolism.

L-Lysine

L-Lysine absorbed from the lumen of the small intestine into the enterocytes by an active transport process.

Potassium iodide

Potassium salts are absorbed from the gastro-intestinal tract. Potassium is excreted in the urine, the faeces and in perspiration. Urinary excretion of potassium continues even when intake is low.

Biotin

Following absorption, biotin is stored in the liver, kidney and pancreas.

Chromium picolinate

Most chromium compounds are soluble at the pH of the stomach, but less soluble hydroxides may form as pH is increased. The environment of the gastrointestinal tract and ligands provided by foods and supplements are important for mineral absorption.

Myo-Inositol

Oral ingestion of inositol is registered to generate a maximal plasma concentration of 36 - 45 mcg. The pharmacokinetic profile of inositol was studied in preterm infants and the estimated volume of distribution was reported to be 0.5115 L/kg. It is thought that inositol can be found bound to plasma proteins.

6.1 Animal toxicology or pharmacology

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the prescribing information.

Bevon drops contain a comprehensive formula of vitamins, minerals and antioxidants specially designed to support health and well-being in adults by unlocking energy and strengthening immunity. Most vitamins, minerals and trace elements are not produced by human body and hence are dependent on dietary supply of these nutrients. Since vitamins, minerals and trace elements are involved in many metabolic processes in the body, an adequate supply of these vital substances contribute to physical and mental well being.

8.1 Incompatibilities

No major incompatibilities are known.

8.2 Shelf-life

18 Months

8.3 Packaging information

A bottle of 15 ml.

8.4 Storage and handing instructions

Store below 25°C. Protect from light. Do not Freeze.

Keep out of reach of children.

FOR PAEDIATRIC USE ONLY.

SHAKE WELL BEFORE USE.

Do not take Bevon Drops :

• if you are allergic (hypersensitive) to any of the ingredients of Bevon drops
• if you suffer from hypercalcaemia (high level of calcium in the blood).

Taking other medicines

Tell your doctor if you are taking or have recently taken/used any of the following medicines as they may interfere with Bevon drops :

• Phenytoin (used to treat epilepsy).
• Tetracycline antibiotics (used to treat infections) such as doxycycline and minocycline.

Please tell your doctor if you are taking or have recently taken/used any other medicines including other vitamin or mineral products medicines obtained without a prescription.

20.04.2022

Azithromycin Tablets IP 250 mg / 500 mg

Azitus 250

Each film coated tablet contains :

Azithromycin Dihydrate IP

equivalent to Azithromycin 250 mg

Excipients q.s.

Colour : Titanium Dioxide IP

Azitus 500

Each film coated tablet contains :

Azithromycin Dihydrate IP

equivalent to Azithromycin 500 mg

Excipients

Colour : Titanium Dioxide IP

Tablet 250 / 500 mg

4.1 Therapeutic indication

• Uncomplicated multidrug resistant enteric fever only
• Acute bacterial sinusitis.
• Acute bacterial otitis media
• Pharyngitis, tonsillitis
• Acute exacerbation of chronic bronchitis
• Mild to moderately severe community acquired pneumonia
• Skin and soft tissue infections
• Uncomplicated Chlamydia trachomatis urethritis and cervicitis

Considerations should be given to official guidance on the appropriate use of antibacterial agents

4.2 Posology and method of administration

Azithromycin should be given as a single daily dose. Duration of the treatment for the different infection diseases is given below.

Adults, children and adolescents with a body weight of 45 kg or over

The total dose is 1500 mg, administered as 500 mg once daily for 3 days. Alternatively, the same total dose (1500 mg) can be administered in a period of 5 days, 500 mg on the first day and 250 mg on day 2 to 5. In the case of uncomplicated Chlamydia trachomatis urethritis and cervicitis, the dosage is 1000 mg as a single oral dose.

For patients who are allergic to penicillin and/or cephalosporins, prescribers should consult local treatment guidelines.

Children and adolescents with a body weight below 45 kg

Azithromycin tablets are not suitable for patients under 45 kg body weight. Other dosage forms are available for this group of patients.

Elderly patients

For elderly patients the same dose as for adults can be applied. Since elderly patients can be patients with ongoing proarrhythmic conditions a particular caution is recommended due to the risk of developing cardiac arrhythmia and torsades de pointes

Patients with renal impairment

Dose adjustment is not required in patients with mild to moderate renal impairment (GFR 10-80 ml/min). Caution should be exercised when Azithromycin is administered to patients with severe renal impairment (GFR < 10 ml/min).

Patients with hepatic impairment

Since Azithromycin is metabolised in the liver and excreted in the bile, the drug should not be given to patients suffering from severe liver disease. No studies have been conducted regarding treatment of such patients with Azithromycin.

Method of administration

Azithromycin film-coated tablets are for oral administration only. The tablets can be taken with or without food. The tablets should be taken with ½ glass of water

4.3 Contraindications

Hypersensitivity to Azithromycin, Erythromycin, any Macrolide or Ketolide antibiotic, or to any of the excipient listed in the formulation.

4.4 Special warnings and precautions for use

Hypersensitivity

As with Erythromycin and other Macrolides, rare serious allergic reactions including angioneurotic oedema and anaphylaxis (rarely fatal), dermatologic reactions including Acute Generalised Exanthematous Pustulosis (AGEP), Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) (rarely fatal) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported. Some of these reactions with Azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Hepatotoxicity

Since the liver is the principal route of elimination for Azithromycin, the use of Azithromycin should be undertaken with caution in patients with significant hepatic disease. Cases of fulminant hepatitis potentially leading to lifethreatening liver failure have been reported with Azithromycin. Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products. In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests / investigations should be performed immediately. Azithromycin administration should be stopped if liver dysfunction has emerged.

Ergot derivatives

In patients receiving Ergot derivatives, Ergotism has been precipitated by co-administration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergotamine derivatives and Azithromycin. However, because of the theoretical possibility of Ergotism, Azithromycin and Ergot derivatives should not be co-administered.

Prolongation of the QT interval

Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with Azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarisation; therefore, caution is required when treating patients :

• With congenital or documented QT prolongation.
• Currently receiving treatment with other active substances known to prolong QT interval such as antiarrhythmics of classes Ia and III, Cisapride and Terfenadine.
• With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia
• With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency

Superinfection

As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms including fungi is recommended.

Clostridium difficile associated diarrhoea

Clostridium difficile associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including Azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Strains of C. difficile producing hypertoxins A and B contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. Therefore, CDAD must be considered in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. Discontinuation of therapy with Azithromycin and the administration of specific treatment for C. difficile should be considered.

Streptococcal infections

Penicillin is usually the first choice for treatment of pharyngitis/tonsillitis due to Streptococcus pyogenes and also for prophylaxis of acute rheumatic fever. Azithromycin is in general effective against streptococcus in the oropharynx, but no data are available that demonstrate the efficacy of Azithromycin in preventing acute rheumatic fever.

Renal impairment

In patients with severe renal impairment (GFR < 10 ml/min) a 33% increase in systemic exposure to Azithromycin was observed.

Myasthenia gravis

Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy. Co-administration with Hydroxychloroquine or Chloroquine

Carefully consider the balance of benefits and risks before prescribing Azithromycin for any patients taking Hydroxychloroquine or Chloroquine, because of the potential for an increased risk of cardiovascular events and cardiovascular mortality.

4.5 Drugs interactions

Antacids

In a pharmacokinetic study investigating the effects of simultaneous administration of antacids with Azithromycin, no effect on overall bioavailability was seen, although peak serum concentrations were reduced by approximately 24%. In patients receiving both Azithromycin and antacids, the drugs should not be taken simultaneously.

Cetirizine

In healthy volunteers, co-administration of a 5-day regimen of Azithromycin with 20 mg Cetirizine at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.

Didanosine (Dideoxyinosine)

Co-administration of 1200 mg/day Azithromycin with 400 mg/day Didanosine in 6 HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of Didanosine as compared with placebo.

Digoxin and Colchicine

Concomitant administration of macrolide antibiotics, including Azithromycin, with P-glycoprotein substrates such as Digoxin and Colchicine, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if Azithromycin and P-glycoprotein substrates such as Digoxin are administered concomitantly, the possibility of elevated serum Digoxin concentrations should be considered. Clinical monitoring, and possibly serum Digoxin levels, during treatment with Azithromycin and after its discontinuation are necessary.

Zidovudine

Single 1000 mg doses and multiple 1200 mg or 600 mg doses of Azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of Zidovudine or its glucuronide metabolite. However, administration of Azithromycin increased the concentrations of phosphorylated Zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.

Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with Erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with Azithromycin.

Ergot derivatives

Due to the theoretical possibility of ergotism, the concurrent use of Azithromycin with Ergot derivatives is not recommended. Pharmacokinetic studies have been conducted between Azithromycin and the following drugs known to undergo significant cytochrome P450 mediated metabolism.

Atorvastatin

Co-administration of Atorvastatin (10 mg daily) and Azithromycin (500 mg daily) did not alter the plasma concentrations of Atorvastatin (based on a HMG CoA-reductase-inhibition assay).

Carbamazepine

In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of Carbamazepine or its active metabolite in patients receiving concomitant Azithromycin.

Cimetidine

In a pharmacokinetic study investigating the effects of a single dose of Cimetidine, given 2 hours before Azithromycin, on the pharmacokinetics of Azithromycin, no alteration of Azithromycin pharmacokinetics was seen.

Coumarin-type oral anticoagulants

In a pharmacokinetic interaction study, Azithromycin did not alter the anticoagulant effect of a single dose of 15 mg Warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of Azithromycin and Coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when Azithromycin is used in patients receiving Coumarin-type oral anticoagulants.

Ciclosporin

In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose of Azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of Ciclosporin, the resulting Ciclosporin Cmax and AUC0-5were found to be significantly elevated (by 24% and 21% respectively), however no significant changes were seen in AUC0-∞. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, Ciclosporin levels should be monitored and the dose adjusted accordingly.

Efavirenz

Co-administration of a single dose of 600 mg Azithromycin and 400 mg Efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.

Fluconazole

Co-administration of a single dose of 1200 mg Azithromycin did not alter the pharmacokinetics of a single dose of 800 mg Fluconazole. Total exposure and half-life of Azithromycin were unchanged by the co-administration of Fluconazole, however, a clinically insignificant decrease in Cmax (18%) of Azithromycin was observed.

Indinavir

Co-administration of a single dose of 1200 mg Azithromycin had no statistically significant effect on the pharmacokinetics of Indinavir administered as 800 mg three times daily for 5 days.

Methylprednisolone

In a pharmacokinetic interaction study in healthy volunteers, Azithromycin had no significant effect on the pharmacokinetics of Methylprednisolone.

Midazolam

In healthy volunteers, co-administration of Azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg dose of Midazolam.

Nelfinavir

Co-administration of Azithromycin (1200 mg) and Nelfinavir at steady state (750 mg three times daily) resulted in increased Azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment was required.

Rifabutin

Co-administration of Azithromycin and Rifabutin did not affect the serum concentrations of either drug. Neutropenia was observed in subjects receiving concomitant treatment of Azithromycin and Rifabutin. Although neutropenia has been associated with the use of Rifabutin, a causal relationship to combination with Azithromycin has not been established.

Sildenafil

In normal healthy male volunteers, there was no evidence of an effect of Azithromycin (500 mg daily for 3 days) on the AUC and C_max of Sildenafil or its major circulating metabolite.

Terfenadine

Pharmacokinetic studies have reported no evidence of an interaction between Azithromycin and Terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however, there was no specific evidence that such an interaction had occurred.

Theophylline

There is no evidence of a clinically significant pharmacokinetic interaction when Azithromycin and Theophylline are co-administered to healthy volunteers.

Triazolam

In 14 healthy volunteers, co-administration of Azithromycin 500 mg on Day 1 and 250 mg on Day 2 with 0.125 mg Triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for Triazolam compared to Triazolam and placebo.

Trimethoprim / Sulfamethoxazole

Co-administration of Trimethoprim/Sulfamethoxazole DS (160 mg/800 mg) for 7 days with Azithromycin 1200 mg on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either Trimethoprim or Sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.

Hydroxychloroquine and Chloroquine

Observational data have shown that co-administration of Azithromycin with Hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events and cardiovascular mortality. Carefully consider the balance of benefits and risks before prescribing Azithromycin for any patients taking Hydroxychloroquine. Similar careful consideration of the balance of benefits and risk should also be undertaken before prescribing Azithromycin for any patients taking Chloroquine, because of the potential for a similar risk with Chloroquine.

4.6 Use in special populations

Pregnancy

Animal reproduction studies have been performed at doses up to moderately maternally toxic dose concentrations. In these studies, no evidence of harm to the foetus due to Azithromycin was found. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Azithromycin should be used during pregnancy only if clearly needed.

Breast-feeding

Limited information available from published literature indicates that Azithromycin is present in human milk at an estimated highest median daily dose of 0.1 to 0.7 mg/kg/day. No serious adverse effects of Azithromycin on the breast-fed infants were observed. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Azithromycin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

4.7 Effects on ability to drive and use machines

No data are available regarding the influence of Azithromycin on a patient's ability to drive or operate machinery. However, the possibility of undesirable effects like dizziness and convulsions should be taken into account when performing these activities.

4.8 Undesirable effects

Azithromycin is well tolerated with a low incidence of side effects

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

4.9 Overdose

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses.

Symptoms

The typical symptoms of an overdose with macrolide antibiotics include reversible loss of hearing, severe nausea, vomiting and diarrhoea.

Treatment

In the event of overdose, the administration of medicinal charcoal and general symptomatic treatment and supportive measures are indicated as required.

5.1 Mechanism of action

The mechanism of action of Azithromycin is based upon the suppression of bacterial protein synthesis by means of binding to the ribosomal 50S sub-unit and inhibition of peptide translocation.

5.2 Pharmacodynamic properties

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable

Table : Antibacterial spectrum of Azithromycin

Methycillin-resistant staphylococci have a very high prevalence of acquired resistance to macrolides and have been placed here because they are rarely susceptible to Azithromycin.

5.3 Pharmacokinetic properties

Absorption

Bioavailability of Azithromycin after oral administration is approximately 37%. Peak plasma concentrations are attained after 2 - 3 hours. The mean maximum concentration observed (Cmax) after a single dose of 500 mg is approximately 0.4 μg/ml.

Distribution

Orally administered Azithromycin is widely distributed throughout the body. In pharmacokinetic studies it has been demonstrated that the concentrations of Azithromycin measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma, which indicates that the agent strongly binds to tissues. Binding to serum proteins varies according to plasma concentration and ranges from 12% at 0.5 microgram/ml up to 52% at 0.05 microgram Azithromycin/ml serum. The mean volume of distribution at steady state (VVSS) has been calculated to be 31.1 l/kg.

At the recommended dose no accumulation appears in the serum. Accumulation appears in tissues where levels are much higher than in serum. Three days after administration of 500 mg as a single dose or in partial doses concentrations of 1,3 - 4,8 μg/g, 0,6 - 2,3 μg/g, 2,0 - 2,8 μg/g and 0 - 0,3 μg/ml have been measured in resp. lung, prostate, tonsil and serum.

Elimination

The terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2 - 4 days. Approximately 12% of an intravenously administered dose is excreted in unchanged form with the urine over a period of 3 days; the major proportion in the first 24 hours. Concentrations of up to 237 μg/ml Azithromycin, 2 days after a 5-day course of treatment, have been found in human bile. Ten metabolites have been identified (formed by N- and O-demethylation, by Hydroxylation of the desosamine and aglycone rings, and by splitting of the cladinose conjugate). Investigations suggest that the metabolites do not play a role in the microbiological activity of Azithromycin.

6.1 Animal toxicology or pharmacology

Phospholipidosis (intracellular phospholipid accumulation) has been observed in several tissues (e.g. eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) of mice, rats, and dogs given multiple doses of Azithromycin. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs. The effect has been shown to be reversible after cessation of Azithromycin treatment. The relevance of this finding to humans receiving Azithromycin in accordance with the recommendations is unknown. Electrophysiological investigations have shown that Azithromycin prolongs the QT interval

Carcinogenic potential

Long-term studies in animals have not been performed to evaluate carcinogenic potential as the drug is indicated for short-term treatment only and there were no signs indicative of carcinogenic activity.

Mutagenic potential

There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro test models.

Reproductive toxicity

In animal studies for embryotoxic effects of the substance, no teratogenic effect was observed in mice and rats. In rats, Azithromycin doses of 100 and 200 mg/kg bodyweight/day led to mild retardation of foetal ossification and in maternal weight gain. In peri- and postnatal studies in rats, mild retardation following treatment with 50 mg/kg/day Azithromycin and above was observed.

Azithromycin tablet contains the active ingredient Azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the,

Chemical name : (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)oxy]-2-ethyl- 3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-

(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one.

Molecular formula : C₃₈H₇₂N₂O₁₂

Molecular weight : 749.00 g/mol

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

Azitus 250 : A blister strip of 10 tablets.

Azitus 500 : A blister strip of 5 tablets.

8.5 Storage and handing instructions

Store below 30°C. Protect from light & moisture

Keep out of reach of children

Azithromycin tablets may be taken with or without food. However, increased tolerability has been observed when tablets are taken with food.

Patients should also be cautioned not to take Aluminium- and Magnesium-containing antacids and Azithromycin simultaneously

The patient should be directed to discontinue Azithromycin immediately and contact the Physician if any signs of an allergic reaction occur.

Patients should be counselled that antibacterial drugs, including Azithromycin, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Azithromycin is prescribed to treat bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Azithromycin or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibacterial which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible.

Azithromycin Oral Suspension IP

Each 5 ml contains :

Azithromycin IP (as Dihydrate)

equivalent to Azithromycin 100 mg

Excipients q.s

Colour : Quinoline Yellow

Flavoured syrupy base

Each 5 ml contains :

Azithromycin IP (as Dihydrate

equivalent to Azithromycin 200 mg

Excipients q.s.

Flavoured syrupy base

Oral suspension 100 / 200 mg

4.1 Therapeutic indication

For susceptible infections including community acquired pneumonia, pelvic inflammatory disease.

4.2 Posology and method of administration

Children and adolescents (< 18 years)

The total dose in children aged 1 year and older is 30 mg/kg administered as 10 mg/kg once daily for three days, or over a period of five days starting with a single dose of 10 mg/kg on the first day, followed by doses of 5 mg/kg per day for the following 4 days, according to the tables shown below. There are limited data on use in children younger than 1 year.

The dose for the treatment of pharyngitis caused by Streptococcus pyogenes is an exception : in the treatment of pharyngitis caused by Streptococcus pyogenes Azithromycin has proved to be effective when it is administered to children as a single dose of 10 mg/kg or 20 mg/kg for 3 days with a maximum daily dose of 500 mg. At these two doses a comparable clinical effect was observed, even if the eradication of the bacteria was more significant at a daily dose of 20 mg/kg. Penicillin is however the drug of first choice in the treatment of pharyngitis caused by Streptococcus pyogenes and the prevention of subsequent rheumatic fever

Patients with renal impairment :

No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10-80 ml/min).

Patients with hepatic impairment :

A dose adjustment is not necessary for patients with mild to moderately impaired liver function

Method of administration

After taking the suspension a bitter after-taste can be avoided by drinking fruit juice directly after swallowing. Azithromycin oral suspension should be given in a single daily dose. The suspension may be taken together with food.

4.3 Contraindications

The use of this product is contraindicated in patients with hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic, or to any of the excipients listed in the formulation.

4.4 Special warnings and precautions for use Hypersensitivity

As with erythromycin and other macrolides, rare serious allergic reactions, including angioneurotic oedema and anaphylaxis (rarely fatal), dermatologic reactions including acute generalised exanthematous pustulosis (AGEP), Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (rarely fatal) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment. If an allergic reaction occurs, the medicinal product should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported with azithromycin. Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products. In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests / investigations should be performed immediately. Azithromycin administration should be stopped if liver dysfunction has emerged. In patients receiving ergot derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be coadministered. As with any antibiotic preparation, observation for signs of superinfection with non- susceptible organisms, including fungi is recommended.

Clostridium difficile associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. In patients with severe renal impairment (GFR <10 ml/min) a 33% increase in systemic exposure to azithromycin was observed.

Cardiovascular Events

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides including azithromycin. Therefore as the following situations may lead to an increased risk for ventricular arrhythmias (including torsade de pointes) which can lead to cardiac arrest, azithromycin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients) such as patients :

With congenital or documented QT prolongation

• Currently receiving treatment with other active substances known to prolong QT interval such as antiarrhythmics of class IA (quinidine and procainamide ) and class III (dofetilide, amiodarone and sotalol), cisapride and terfenadine; antipsychotic agents such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin
• With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesemia
• With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency

Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results. Some observational studies have identified a rare short term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including azithromycin. Consideration of these findings should be balanced with treatment benefits when prescribing azithromycin. Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy. Safety and efficacy for the prevention or treatment of Mycobacterium aviumcomplex in children have not been established.

The following should be considered before prescribing azithromycin :

Azithromycin oral suspension is not suitable for treatment of severe infections where a high concentration of the antibiotic in the blood is rapidly needed.

Azithromycin is not the first choice for the empiric treatment of infections in areas where the prevalence of resistant isolates is 10% or more.

In areas with a high incidence of erythromycin A resistance, it is especially important to take into consideration the evolution of the pattern of susceptibility to azithromycin and other antibiotics.

As for other macrolides, high resistance rates of Streptococcus pneumoniae (> 30 %) have been reported for azithromycin in some European countries. This should be taken into account when treating infections caused by Streptococcus pneumoniae.

Pharyngitis / tonsilitis

Azithromycin is not the substance of first choice for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes. For this and for the prophylaxis of acute rheumatic fever penicillin is the treatment of first choice.

Sinusitis

Often, azithromycin is not the substance of first choice for the treatment of sinusitis

Acute otitis media

Often, azithromycin is not the substance of first choice for the treatment of acute otitis media.

Skin and soft tissue infections

The main causative agent of soft tissue infections, Staphylococcus aureus, is frequently resistant to azithromycin. Therefore, susceptibility testing is considered a precondition for treatment of soft tissue infections with azithromycin.

Infected burn wounds

Azithromycin is not indicated for the treatment of infected burn wounds

Sexually transmitted disease

In case of sexually transmitted diseases a concomitant infection by T. pallidum should be excluded.

Neurological or psychiatric diseases

Azithromycin should be used with caution in patients with neurological or psychiatric disorders.

Neurological or psychiatric diseases

Azithromycin should be used with caution in patients with neurological or psychiatric disorders.

4.5 Drugs interactions

Antacids

In a pharmacokinetic study investigating the effects of simultaneous administration of antacid with azithromycin, no effect on overall bioavailability was seen although peak serum concentrations were reduced by approximately 25%. In patients receiving both azithromycin and antacids, the medicinal products should not be taken simultaneously.

Cetirizine

In healthy volunteers, coadministration of a 5-day regimen of azithromycin with cetirizine 20 mg at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.

Didanosine (Dideoxyinosine)

Coadministration of 1200 mg/day azithromycin with 400 mg/day didanosine in 6 HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared with placebo.

Digoxin and colchicine (P-gp substrates)

Concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin and colchicine, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if azithromycin and P-gp substrates such as digoxin are administered concomitantly, the possibility of elevated serum concentrations of the substrate should be considered

Zidovudine

Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients. Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin

Ergot

Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended. Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450 mediated metabolism. Ergotamine derivatives : Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended. Astemizole, alfentanil There are no known data on interactions with astemizole or alfentanil. Caution is advised in the co-administration of these medicines with Azithromycin because of the known enhancing effect of these medicines when used concurrently with the macrolid antibiotic erythromycin.

Atorvastatin

Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay). However, post-marketing cases of rhabdomyolysis in patients receiving azithromycin with statins have been reported.

Carbamazepine

In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.

Cisapride

Cisapride is metabolized in the liver by the enzyme CYP 3A4. Because macrolides inhibit this enzyme, concomitant administration of cisapride may cause the increase of QT interval prolongation, ventricular arrhythmias and torsades de pointes

Cimetidine

In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.

Coumarin-type oral anticoagulants

In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when azithromycin is used in patients receiving coumarin-type oral anticoagulants.

Cyclosporin

In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporin, the resulting cyclosporin Cmax and AUC0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.

Efavirenz

Co-administration of a 600 mg single dose of azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.

Fluconazole

Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the co-administration of fluconazole, however, a clinically insignificant decrease in Cmax (18%) of azithromycin was observed.

Indinavir

Co-administration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.

Methylprednisolone

In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.

Midazolam

In healthy volunteers, co-administration of azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg dose of midazolam.

Nelfinavir

Co-administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment is required

Rifabutin

Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either medicinal product. Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established.

Sildenafil

In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite.

Terfenadine

Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however there was no specific evidence that such an interaction had occurred.

Theophylline

There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.

Triazolam

In 14 healthy volunteers, co-administration of azithromycin 500 mg on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.

Trimethoprim / sulfamethoxazole

Co-administration of trimethoprim/sulfamethoxazole (160 mg/800 mg) for 7 days with azithromycin 1200 mg on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies. Substances that prolong the QT interval Azithromycin should not be used concomitantly with other active substances that prolong the QT interval

4.6 Use in special populations

Pregnancy

There are no adequate data from the use of Azithromycin in pregnant women. In reproduction toxicity studies in animals azithromycin was shown to pass the placenta, but no teratogenic effects were observed. The safety of azithromycin has not been confirmed with regard to the use of the active substance during pregnancy. Therefore Azithromycin should only be used during pregnancy if the benefit outweighs the risk.

Breastfeeding

Azithromycin has been reported to be secreted into human breast milk, but there are no adequate and well-controlled clinical studies in breastfeeding women that have characterized the pharmacokinetics of azithromycin excretion into human breast milk.

Fertility

In fertility studies conducted in rat, reduced pregnancy rates were noted following administration of azithromycin. The relevance of this finding to humans is unknown.

4.7 Effects on ability to drive and use machines

There is no evidence to suggest that azithromycin may have an effect on a patient's ability to drive or operate machinery. Visual impairment and vision blurred may have an effect on a patient's ability to drive or operate machinery.

4.8 Undesirable effects

Adverse reactions possibly or probably related to Mycobacterium Avium Complex prophylaxis and treatment base Adverse reactions possibly or probably related to Mycobacterium Avium Complex prophylaxis and treatment based on clinical trial experience and post-marketing surveillance. These adverse reactions differ from those reported with immediate release or the prolonged release formulations, either in kind or in frequency :

5.1 Mechanism of action

Azithromycin is an azalide, a sub-class of the macrolide antibiotics. By binding to the 50S-ribosomal sub-unit, azithromycin avoids the translocation of peptide chains from one side of the ribosome to the other. As a consequence of this, RNAdependent protein synthesis in sensitive organisms is prevented.

5.2 Pharmacodynamic properties

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Table : Antibacterial spectrum of Azithromycin

* Methycillin-resistant staphylococci have a very high prevalence of acquired resistance to macrolides and have been placed here because they are rarely susceptible to azithromycin.

5.3 Pharmacokinetic properties

Absorption

The biological availability of azithromycin after oral administration is approximately 37%. Peak plasma levels are achieved 2-3 hours after taking the medicinal product.

Distribution

After oral administration, azithromycin is distributed throughout the entire body. Pharmacokinetic studies have shown clearly higher azithromycin levels in the tissues than in the plasma (up to 50 times the maximum observed concentration in plasma). This indicates that the substance is bound in the tissues in considerable quantities. Concentrations in the infected tissues, such as lungs, tonsil and prostate are higher than the MRC90 of the most frequently occurring pathogens after a single dose of 500 mg. The protein binding of azithromycin in serum is variable and varies, depending on the serum concentration, from 52% at 0.05 mg/l to 12% at 0.5 mg/l. The steady state distribution volume is 31.1 l/kg.

Elimination

The terminal plasma-elimination half-life closely follows the tissue depletion half-life from 2 to 4 days. Approximately 12% of an intravenously administered dose of azithromycin is, over a period of 3 days, excreted unchanged in the urine. High concentrations of unchanged azithromycin were found in human bile. In this, ten metabolites were also detected (formed by N- and O- desmethylation, by hydroxylation of the desosamin and aglycon rings and by splitting the cladinose conjugate). A comparison of fluid chromatography and microbiological assessment methods shows that the metabolites are microbiologically inactive.

6.1 Animal toxicology or pharmacology

In animal tests in which the doses used amounted to 40 times the clinical therapeutic doses, azithromycin was found to have caused reversible phospholipidosis, but as a rule no true toxicological consequences were observed which were associated with this. The relevance of this finding to humans receiving azithromycin in accordance with the recommendations is unknown. Electrophysiological investigations have shown that azithromycin prolongs the QT interval. Mutagenic potential : There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro test models. Reproductive toxicity : In embryotoxicity studies in mice and rats no teratogenic effects were observed. In rats, azithromycin dosages of 100 and 200 mg/kg bodyweight/day led to slight retardations in fetal ossification and in maternal weight gain. In peri-/postnatal studies in rats, slight retardations in physical development and delay in reflex development were observed following treatment with 50 mg/kg/day azithromycin and above.

Azithromycin suspension contains the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the

Chemical name : (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)- βD-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one.

Molecular formula : C₃₈H₇₂N₂O₁₂

Molecular weight : 749.0 g/mol

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

30 Months

8.3 Packaging information

A bottle of 30 ml.

8.4 Storage and handing instructions

Store below 25°C. Protect from light.

Keep out of reach of children.

• Azithromycin suspension may be taken with or without food. However, increased tolerability has been observed when tablets are taken with food.
• Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and azithromycin simultaneously.
• The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur.
• Patients should be counselled that antibacterial drugs, including azithromycin, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When azithromycin is prescribed to treat bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by azithromycin or other antibacterial drugs in the future
• Diarrhea is a common problem caused by antibacterial which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible.

Dispersible Co-Amoxiclav Tablets BP [200 mg + 28.5 mg]

Each uncoated dispersible tablet contains :

Amoxycillin Trihydrate IP

equivalent to Amoxycillin 200 mg

Potassium Clavulanate Diluted IP

equivalent to Clavulanic Acid 28.5 mg

Excipients q.s

Dispersible Tablet, [200 mg + 28.5 mg]

4.1 Therapeutic indication

For the treatment of LRTI infections (e.g. Pneumonia, Bronchitis), Acute otitis media, Sinusitis & UTI, Skin and soft tissue infections, Bone and joint infections.

4.2 Posology and method of administration

Patients aged 2 years and older

Usual dosages for the treatment of infection

There is insufficient experience with Augpen KID DT to make dosage recommendations for children aged below 2 months.

Infants with immature kidney function

For infants with immature renal function, Augpen KID DT is not recommended.

Renal impairment

For children with a GFR of > 30 mL/min no adjustment in dosage is required. For children with a GFR of < 30 mL/min, Augpen KID DT is not recommended.

Hepatic impairment

Dose with caution; monitor hepatic function at regular intervals. There is, as yet, insufficient evidence on which to base a dosage administration.

Directions for use

Disperse the tablet in a teaspoonful of previously boiled & cooled water before administration.

4.3 Contraindications

• Patients with a history of hypersensitivity to beta-lactams, e.g. penicillin and cephalosporins
• Patients with a previous history of Augpen-associated jaundice/hepatic dysfunction.

4.4 Special warnings and precautions for use

Before initiating therapy with Augpen KID DT, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity (see Contraindications). If an allergic reaction occurs, Augpen KID DT therapy must be discontinued and appropriate alternative therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with Adrenaline. Oxygen, intravenous (I.V.) steroids and airway management (including intubation) may also be required. Augpen KID DT should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of Amoxycillin. Prolonged use may also occasionally result in overgrowth of non-susceptible organisms. Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving Augpen KID DT and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation. Changes in liver function tests have been observed in some patients receiving Augpen KID DT. The clinical significance of these changes is uncertain but Augpen KID DT should be used with caution in patients with evidence of hepatic dysfunction. Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for up to six weeks after treatment has ceased.

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of Amoxycillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of Amoxycillin crystalluria.

4.5 Drugs interactions

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of Amoxycillin. Concomitant use with Augpen KID DT may result in increased and prolonged blood levels of Amoxycillin but not of Clavulanate. Concomitant use of allopurinol during treatment with Amoxycillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of Augpen KID DT and Allopurinol. In common with other antibiotics, Augpen KID DT may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives. In the literature there are rare cases of increased international normalised ratio in patients maintained on Acenocoumarol or warfarin and prescribed a course of Amoxycillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of Augpen KID DT. In patients receiving Mycophenolate Mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid of approximately 50% has been reported following commencement of oral Amoxycillin plus Clavulanic Acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure.

4.6 Use in special populations

Pregnancy and lactation

Reproduction studies in animals (mice and rats) with orally and parenterally administered Augpen KID DT have shown no teratogenic effects. In a single study in women with preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with Augpen may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the Physician. Augpen may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no detrimental effects for the infant.

4.7 Effects on ability to drive and use machines

Adverse effects on the ability to drive or operate machinery have not been observed.

4.8 Undesirable effects

Data from large clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at < 1/10,000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.

Infections and infestations

Common : Mucocutaneous candidiasis

Blood and lymphatic system disorders

Rare : Reversible leucopenia (including neutropenia) and thrombocytopenia. Very rare : Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time.

Immune system disorders

Very rare : Angioneurotic oedema, Anaphylaxis, Serum sickness-like syndrome, Hypersensitivity vasculitis

Nervous system disorders

Uncommon : Dizziness, Headache Very rare : Reversible hyperactivity, Aseptic meningitis, Convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Gastrointestinal disorders

Adults

Very common : Diarrhoea

Common : Nausea, Vomiting

Children

Common : Diarrhoea, Nausea, Vomiting

All populations

Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking Augpen KID DT at the start of a meal. Uncommon : Indigestion Very rare : Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis), black hairy tongue, superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.

Hepatobiliary disorders

Uncommon : A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown. Very rare : Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins. Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects.

Skin and subcutaneous tissue disorders

Uncommon : Skin rash, pruritus, urticaria

Rare : Erythema multiforme

Very rare : Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, Acute Generalised Exanthematous Pustulosis (AGEP), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.

Renal and urinary disorders

Very rare : Interstitial nephritis, Crystalluria

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to :medico@zuventus.com

4.9 Overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Gastrointestinal symptoms may be treated symptomatically with attention to the water-electrolyte balance. Amoxycillin crystalluria, in some cases leading to renal failure, has been observed. Augpen can be removed from the circulation by haemodialysis

5.1 Mechanism of action

Amoxycillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.

5.2 Pharmacodynamic properties

Amoxycillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of Amoxycillin alone does not include organisms which produce these enzymes. Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes thereby preventing inactivation of Amoxycillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect.

The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

5.3 Pharmacokinetic properties

Absorption

Amoxycillin and Clavulanic Acid, are fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Following oral administration, Amoxycillin and Clavulanic Acid are approximately 70% bioavailable. The plasma profiles of both components are similar and the time to peak plasma concentration (Tmax) in each case is approximately one hour.

The pharmacokinetic results for a study, in which Amoxycillin/Clavulanic Acid (250 mg/125 mg tablets three times daily) was administered in the fasting state to groups of healthy volunteers are presented below.

Amoxycillin and Clavulanic Acid serum concentrations achieved with Amoxycillin/Clavulanic Acid are similar to those produced by the oral administration of equivalent doses of Amoxycillin or Clavulanic Acid alone.

Distribution

About 25% of total plasma Clavulanic Acid and 18% of total plasma Amoxycillin is bound to protein. The apparent volume of distribution is around 0.3 - 0.4 l/kg for Amoxycillin and around 0.2 l/kg for Clavulanic Acid. Following intravenous administration, both Amoxycillin and Clavulanic Acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxycillin does not adequately distribute into the cerebrospinal fluid. From animal studies there is no evidence for significant tissue retention of drug-derived material for either component. Amoxycillin, like most penicillin, can be detected in breast milk. Trace quantities of Clavulanic Acid can also be detected in breast milk. Both Amoxycillin and Clavulanic Acid have been shown to cross the placental barrier.

Biotransformation

Amoxycillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolized in man and eliminated in urine and faeces, and as carbon dioxide in expired air.

Elimination

The major route of elimination for Amoxycillin is via the kidney, whereas for Clavulanic Acid it is by both renal and non-renal mechanisms. Amoxycillin/Clavulanic Acid has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70% of the Amoxycillin and approximately 40 to 65% of the Clavulanic Acid are excreted unchanged in urine during the first 6 h after administration of single Augpen KID DT Tablets [200 mg + 28.5 mg]. Various studies have found the urinary excretion to be 50 - 85% for Amoxycillin and between 27-60% for Clavulanic Acid over a 24-hour period. In the case of Clavulanic Acid, the largest amount of drug is excreted during the first 2 hours after administration. Concomitant use of probenecid delays Amoxycillin excretion but does not delay renal excretion of Clavulanic Acid.

6.1 Animal toxicology or pharmacology

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, genotoxicity and toxicity to reproduction. Repeat dose toxicity studies performed in dogs with Amoxycillin/Clavulanic Acid demonstrate gastric irritancy and vomiting, and discoloured tongue. Carcinogenicity studies have not been conducted with Amoxycillin/Clavulanic Acid.

Augpen KID DT is an oral antibacterial combination consisting of Amoxycillin and the beta-lactamase inhibitor, Clavulanate Potassium (the Potassium salt of Clavulanic Acid).

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack

8.3 Packaging information

Alu-Alu blister strip of 10 tablets / 2 tablets (PS).

8.4 Storage and handing instructions

Store below 25°C. Protect from light & moisture.

Keep out of reach of children.

Patients should be informed that Augpen KID DT may be taken every 8 hours or every 12 hours, depending on the dose prescribed. Each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset. Patients should be counseled that antibacterial drugs, including Augpen KID DT, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Augpen KID DT is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may : (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Augpen KID DT or other antibacterial drugs in the future. Counsel patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, patients should contact their physician. Patients should be advised to keep suspension refrigerated. Shake well before using. When dosing a child with the suspension (liquid) of Augpen KID DT, use a dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use. Bottles of suspension of Augpen KID DT may contain more liquid than required. Follow your doctor’s instructions about the amount to use and the days of treatment your child requires. Discard any unused medicine. Patients should be aware that Augpen KID DT contains a penicillin class drug product that can cause allergic reactions in some individuals.

05 September 2022