Macrizine

Uses

Macrizine is used for the treatment of seasonal allergic rhinitis and conjunctivitis, perennial allergic rhinitis, pruritus and urticaria. It is also used in allergen induced asthma.

Macrizine is also used to associated treatment for these conditions: Chronic Idiopathic Urticaria, Flu caused by Influenza, Perennial Allergic Rhinitis (PAR), Pollen Allergy, Respiratory Allergy, Seasonal Allergic Rhinitis

How Macrizine works

Macrizine, a metabolite of hydroxyzine, is an antihistamine drug. Its main effects are achieved through selective inhibition of peripheral H1 receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models. In vivo and ex vivo animal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors other than the H1 receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain. Ex vivo studies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H1 receptors significantly .

Dosage

Macrizine dosage

Tablet:

• Adults and children over 6 years: 1 tablet (10 mg) once daily or ½ tablet twice daily.
• Children 2-6 years: ½ tablet once daily.

Syrup:

• Adults and children over 6 years: 2 teaspoonful (10 mg) once daily or 1 teaspoon (5 mg) twice daily.
• Children 2-6 years: 1 teaspoonful once daily or ½ teaspoon twice daily.

Side Effects

Macrizine dihydrochloride is well tolerated. Lower incidence of sedation, headache, dry mouth, and gastrointestinal disturbances may occur. It does not produce anticholinergic effects.

Toxicity

Oral LD50 (rat): 365 mg/kg; Intraperitoneal LDLO (mouse): 138 mg/kg; Oral TDLO (rat): 50 mg/kg; Oral TDLO (mouse): 0.1 mg/kg .

Carcinogenesis and mutagenesis: In a 2-year carcinogenicity study in rats, cetirizine was not shown to be carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults). In a 2-year carcinogenicity study in mice, cetirizine administration lead to an incidence of benign liver tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults). The clinical significance of these findings during long-term use of cetirizine is unknown at this time .

Macrizine 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 rats .

Impairment of fertility

In a fertility and reproduction study in mice, cetirizine did not negatively impact fertility at an oral dose of 64 mg/kg (approximately 25 times the maximum recommended daily oral dose in adults) .

Pregnancy Category B:

In mice, rats, and rabbits, cetirizine was not teratogenic at oral doses up to 96, 225, and 135 mg/kg, respectively (approximately 40, 180 and 220 times the maximum recommended daily oral dose in adults). There are no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, cetirizine should be used in pregnancy only if clearly needed .

Use in breastfeeding/nursing

Macrizine has been reported to be excreted in human breast milk. The use of cetirizine in nursing mothers is not recommended .

Precaution

Caution should be exercised when driving a car or operating a heavy machinery. Concurrent use of cetirizine with alcohol or other CNS depressants should be avoided because additional reduction in alertness and CNS performance may occur.

Interaction

No clinically significant drug interactions have been found with theophylline, azithromycin, pseudoephedrine, ketoconazole or erythromycin and with some other drugs.

Food Interaction

• Avoid alcohol.
• Take with or without food. The absorption is unaffected by food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Macrizine Drug Interaction

Moderate: diphenhydramine, diphenhydramineUnknown: aspirin, aspirin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, fluticasone nasal, fluticasone nasal, albuterol, albuterol, montelukast, montelukast, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Macrizine Disease Interaction

Moderate: alcohol, renal/liver disease

Volume of Distribution

Apparent volume of distribution: 0.44 +/- 0.19 L/kg .

Elimination Route

Macrizine was rapidly absorbed with a time to maximum concentration (Tmax) of about 1 hour after oral administration of tablets or syrup formulation in adult volunteers . Bioavailability was found to be similar between the tablet and syrup dosage forms. When healthy study volunteers were given several doses of cetirizine (10 mg tablets once daily for 10 days), a mean peak plasma concentration (Cmax) of 311 ng/mL was measured .

Effect of food on absorption

Food had no effect on cetirizine exposure (AUC), however, Tmax was delayed by 1.7 hours and Cmax was decreased by 23% in the fed state .

Half Life

Plasma elimination half-life is 8.3 hours .

Clearance

Apparent total body clearance: approximately 53 mL/min .

Macrizine is mainly eliminated by the kidneys , . Dose adjustment is required for patients with moderate to severe renal impairment and in patients on hemodialysis .

Elimination Route

Mainly eliminated in the urine , .

Between 70 – 85% of an orally administered dose can be found in the urine and 10 – 13% in the feces .

Pregnancy & Breastfeeding use

Pregnancy category B. There are no adequate and well controlled studies in pregnant women. Macrizine should be used during pregnancy only if clearly needed. Macrizine has been reported to be excreted in human breast milk. As large amount of drugs are excreted in human milk, use of Macrizine in nursing mother is not recommended.

Contraindication

Macrizine Dihydrochloride is contraindicated in those patients with a known hypersensitivity to it or any of its ingredients or hydroxyzine.

Acute Overdose

Symptoms: Confusion, dizziness, fatigue, headache, malaise, restlessness, sedation, somnolence, diarrhoea, mydriasis, pruritus, stupor, tachycardia, tremor, and urinary retention.

Management: Symptomatic and supportive treatment. Gastric lavage may be done shortly following ingestion.

Storage Condition

Store between 20-25°C. Syrup: Store between 2-8°C.

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