Elriz D Tablet

Levocetirizine HCl 5 mg & Pseudoephedrine HCl 120 mg SR Tablets

Each uncoated tablet contains

Levocetirizine HCl IP……………………………. 5 mg

Pseudoephedrine HCl IP……………………… 120 mg (as sustained release)

Excipients q.s.

Tablet Levocetrizine & Pseudoephedrine (5 mg + 120 mg)

4.1Therapeutic indications

For the treatment of seasonal allergic rhinitis.

4.2 Posology and method of administration

One tablet once daily.

4.3 Contraindications

• Hypersensitivity to the active substance, to cetirizine, to hydroxyzine, to pseudoephedrine or to any other piperazine derivatives.
• Patients with end stage renal disease with estimated Glomerular Filtration Rate (eGFR) below 15 ml/min (requiring dialysis treatment).
• Concomitant use of other sympathomimetic decongestants, beta-blockers or monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOI treatment. The concomitant use of MAOIs may cause a rise in blood pressure and/or hypertensive crisis.
• Cardiovascular disease including hypertension
• Diabetes mellitus
• Phaeochromocytoma
• Hyperthyroidism
• Closed angle glaucoma
• Severe acute or chronic kidney disease/renal failure

4.4 Special warnings and precautions for use

Precaution is recommended with concurrent intake of alcohol.

Caution should be taken in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as levocetirizine may increase the risk of urinary retention. Caution should be taken in patients with epilepsy and patients at risk of convulsion as levocetirizine may cause seizure aggravation.

Response to allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Pruritus may occur when levocetirizine is stopped even if those symptoms were not present before treatment initiation. The symptoms may resolve spontaneously. In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.

Patients with difficulty in urination and/or enlargement of the prostate, or patients with thyroid disease who are receiving thyroid hormones should not take pseudoephedrine unless directed by a physician.

Caution should be exercised when using the product in the presence of severe hepatic impairment or moderate to severe renal impairment and in occlusive vascular disease. If any of the following occur, this product should be stopped

• Hallucinations
• Restlessness
• Sleep disturbances

Severe Skin reactions

Severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) may occur with pseudoephedrine-containing products. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of this medicine should be discontinued, and appropriate measures taken if needed.

Ischaemic colitis

Some cases of ischaemic colitis have been reported with pseudoephedrine. Pseudoephedrine should be discontinued, and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.

Ischaemic optic neuropathy

Cases of ischaemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.

Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS)

Cases of PRES and RCVS have been reported with the use of pseudoephedrine-containing products. The risk is increased in patients with severe or uncontrolled hypertension, or with severe acute or chronic kidney disease/renal failure.

Pseudoephedrine should be discontinued and immediate medical assistance sought if the following symptoms occur: sudden severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. Most reported cases of PRES and RCVS resolved following discontinuation and appropriate treatment.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed with levocetirizine (including no studies with CYP3A4 inducers); studies with the racemate compound cetirizine demonstrated that there were no clinically relevant adverse interactions (with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole and pseudoephedrine). A small decrease in the clearance of cetirizine (16%) was observed in a multiple dose study with theophylline (400 mg once a day); while the disposition of theophylline was not altered by concomitant cetirizine administration.

In a multiple dose study of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), the extent of exposure to cetirizine was increased by about 40% while the disposition of ritonavir was slightly altered (-11%) further to concomitant cetirizine administration.

The extent of absorption of levocetirizine is not reduced with food, although the rate of absorption is decreased.

In sensitive patients the concurrent administration of cetirizine or levocetirizine and alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.

• MAOIs and/or RIMAs: Pseudoephedrine exerts its vasoconstricting properties by stimulating α -adrenergic receptors and displacing noradrenaline from neuronal storage sites. Since monoamine oxidase inhibitors (MAOIs) impede the metabolism of sympathomimetic amines and increase the store of releasable noradrenaline in adrenergic nerve endings, MAOIs may potentiate the pressor effect of pseudoephedrine. This product should not be used in patients taking monoamine inhibitors or within 14 days of stopping treatment as there is an increased risk of hypertensive crisis.
• Moclobemide: Risk of hypertensive crisis.
• Antihypertensives: Because of its pseudoephedrine content, this product may partially reverse the hypotensive action of antihypertensive drugs which interfere with sympathetic activity including bretylium, betanidine, guanethedine, debrisoquine, methyldopa, adrenergic neurone blockers and beta-blockers.
• Cardiac glycosides: Increased risk of dysrhythmias.
• Ergot alkaloids (ergotamine & methysergide): Increased risk of ergotism.
• Appetite suppressants and amphetamine-like psychostimulants: Risk of hypertension.
• Oxytocin: Risk of hypertension.
• Anticholinergic drugs: Enhances effects of anticholinergic drugs (such as Tricyclic antidepressants).
• Anaesthetic agents: Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.

4.6 Use in special populations

Pregnancy

The use of Elriz D tablet may be considered during pregnancy, if necessary.

Lactation

Elriz D tablet has been shown to be excreted in human milk. Adverse reactions associated with the drug may be observed in breastfed infants. Therefore, caution should be exercised when prescribing it to lactating women.

4.7 Effects on ability to drive and use machines

Elriz D Tablet may decrease alertness, affect your vision or make you feel sleepy and dizzy. Do not drive if these symptoms occur.

4.8 Undesirable effects

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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 is no known specific antidote. Should overdose occur, symptomatic or supportive treatment is recommended. Gastric lavage may be considered shortly after ingestion of the drug.

5.1 Mechanism of action/ Pharmacodynamic properties

Levocetrizine

Levocetirizine, the (R) enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receptors.

Binding studies revealed that levocetirizine has high affinity for human H1-receptors (Ki = 3.2 nmol/l). Levocetirizine has an affinity 2-fold higher than that of cetirizine (Ki = 6.3 nmol/l). Levocetirizine dissociates from H1-receptors with a half-life of 115 ± 38 min. After single administration, levocetirizine shows a receptor occupancy of 90% at 4 hours and 57% at 24 hours.

Pharmacodynamic studies in healthy volunteers demonstrate that, at half the dose, levocetirizine has comparable activity to cetirizine, both in the skin and in the nose.

Pseudoephedrine

Pseudoephedrine has direct and indirect sympathomimetic activity and is an orally effective upper respiratory tract decongestant.

Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation in systolic blood pressure and considerably less potent in causing stimulation of the central nervous system.

5.2 Pharmacokinetic Properties

Levocetrizine

Absorption

Levocetirizine is rapidly and extensively absorbed following oral administration. In adults, peak plasma concentrations are achieved 0.9 h after dosing. Steady state is achieved after two days. Peak concentrations are typically 270 ng/ml and 308 ng/ml following a single and a repeated 5 mg o.d. dose, respectively. The extent of absorption is dose-independent and is not altered by food, but the peak concentration is reduced and delayed.

Distribution

No tissue distribution data are available in humans, neither concerning the passage of levocetirizine through the blood-brain-barrier. In rats and dogs, the highest tissue levels are found in liver and kidneys, the lowest in the CNS compartment. In humans, levocetirizine is 90% bound to plasma proteins. The distribution of levocetirizine is restrictive, as the volume of distribution is 0.4 l/kg.

Biotransformation

The extent of metabolism of levocetirizine in humans is less than 14% of the dose and therefore differences resulting from genetic polymorphism or concomitant intake of enzyme inhibitors are expected to be negligible. Metabolic pathways include aromatic oxidation, N- and O- dealkylation and taurine conjugation. Dealkylation pathways are primarily mediated by CYP 3A4 while aromatic oxidation involved multiple and/or unidentified CYP isoforms. Levocetirizine had no effect on the activities of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 at concentrations well above peak concentrations achieved following a 5 mg oral dose.

Due to its low metabolism and absence of metabolic inhibition potential, the interaction of levocetirizine with other substances, or vice-versa, is unlikely.

Elimination

The plasma half-life in adults is 7.9 ± 1.9 hours. The half-life is shorter in small children. The mean apparent total body clearance in adults is 0.63 ml/min/kg. The major route of excretion of levocetirizine and metabolites is via urine, accounting for a mean of 85.4% of the dose. Excretion via feces accounts for only 12.9% of the dose. Levocetirizine is excreted both by glomerular filtration and active tubular secretion.

Pseudoephedrine

Pseudoephedrine is rapidly and completely absorbed after oral administration. After an oral dose of 180 mg to man, peak plasma concentrations of 500-900 ng/ml were obtained about 2 hours post dose. The plasma half-life was about 5.5 hours and was increased in subjects with alkaline urine and decreased in subjects with acid urine. The only metabolism was N-demethylation which occurred to a small extent. Excretion was mainly via the urine.

6.1 Animal Toxicology or Pharmacology

Levocetrizine

No carcinogenicity studies have been performed with levocetirizine. However, evaluation of cetirizine carcinogenicity studies are relevant for determination of the carcinogenic potential of levocetirizine. In a 2-year carcinogenicity study, in rats, cetirizine was not carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults, approximately 10 times the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 15 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). In a 2-year carcinogenicity study in mice, cetirizine caused an increased incidence of benign hepatic tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults, approximately 4 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 6 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). No increased incidence of benign tumors was observed at a dietary dose of 4 mg/kg (approximately 2 times the maximum recommended daily oral dose in adults, equivalent to the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 2 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). The clinical significance of these findings during long-term use of levocetirizine dihydrochloride tablets is not known. Levocetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and in vivo micronucleus test in mice. In a fertility and general reproductive performance study in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the recommended daily oral dose in adults on a mg/m basis).

Pseudoephedrine

Toxicology: Acute toxicity studies in animals have demonstrated that pseudoephedrine has a relatively high safety margin. However, at high doses, it can cause central nervous system stimulation, cardiovascular effects, and gastrointestinal disturbances.

Chronic Toxicity: Long-term studies in animals have indicated that chronic exposure to pseudoephedrine does not result in significant adverse effects at therapeutic doses. However, high doses can lead to hypertrophy of the heart and other organs.

Genotoxicity and Carcinogenicity: Pseudoephedrine has not shown any genotoxic or carcinogenic potential in standard assays.

Elriz D tablet consists of two medicines: Levocetirizine (antihistamine) and Pseudoephedrine (decongestant). Levocetirizine belongs to the class of antihistamines or anti-allergic that works by blocking the action of histamine, a substance responsible for causing allergic reactions.

8.1 Incompatibilities

Not applicable

8.2 Shelf Life

Refer on pack

8.3 Packaging Information

8.4 Storage and handing Instructions

• You have been prescribed Elriz D Tablet for the treatment of allergy symptoms such as sneezing, runny nose, watery eyes, etc.
• Stop taking Elriz D Tablet at least three days before taking an allergy test as it can affect the test results.
• Do not discontinue use without consulting your doctor, even if you feel better.
• If you drink alcohol while you are taking Elriz D Tablet, be aware of its effects on you and do not drink more than moderate amounts.
• Keep sipping water or try chewing sugar-free gum to get relief from dryness in the mouth.
• Inform your doctor if you are taking any other medications, e.g., anti-depressants.

17.12.2024