Acuzyrt Syrup

ACUZYRT SYRUP is indicated for the treatment of allergic conditions responding to a histamine H1 receptor antagonist:

• Respiratory: Allergic rhinitis, hay fever.
• Cutaneous: Allergic skin conditions associated with pruritus, e.g. urticaria.

Posology

Adults or children 12 years of age or older: 10 mg daily or 10 mL (two medicine measures), once daily.

Children 6 to 12 years old: 10 mg daily: either as a single dose (10 mL) (two medicine measures), or as divided doses of 5 mL (one medicine measure) in the morning and 5 mL (one medicine measure) in the evening.

Children 2 to 6 years old: 5 mg daily: either as a single dose (5 mL) (one medicine measure), or as divided doses of 2.5 mL (half a medicine measure) in the morning and 2.5 mL (half a medicine measure) in the evening.

Missed dose

Doctors should advise patients who forget to take ACUZYRT SYRUP to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

Special populations

Elderly: At present there is no data to suggest that the dose needs to be reduced in elderly patients.
Renal impairment: In patients with renal insufficiency (creatinine clearance less than 40 mL/min), dosage should be reduced to half the usual recommended dose (see section 4.3.)
Hepatic impairment: The dosage should be reduced to half the recommended daily dose in patients with moderate to severe hepatic impairment.
Paediatric population: ACUZYRT SYRUP is contraindicated in children under the age of two years, as safety and efficacy have not been demonstrated (see section 4.3.)

Method of administration

Oral administration

ACUZYRT SYRUP is contraindicated in:

• Hypersensitivity to cetirizine, hydroxyzine, any piperazine derivatives or to any of the ingredients of ACUZYRT SYRUP.
• Patients with severe renal impairment at less than 30 mL/min creatinine clearance.
• Safety in pregnancy and lactation has not been established (see section 4.6).
• Children under the age of two years, as safety and efficacy have not been demonstrated.

• ACUZYRT SYRUP lacks significant sedative effects. Patients should, however, be warned that a small number of individuals may experience sedation. Sedative effects, when they occur, may diminish after a few days of treatment.
• At therapeutic doses, no clinically significant interactions have been demonstrated with alcohol (for a blood alcohol level of 0,5 g/L). Nevertheless, precaution is recommended if alcohol is taken concomitantly (see section 4.5). It is advisable to avoid excessive alcohol consumption. Caution should be taken in patients with predisposition factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as ACUZYRT SYRUP may increase the risk of urinary retention.
• Caution in epileptic patients and patients at risk of convulsions is recommended.
• Allergy skin tests are inhibited by ACUZYRT SYRUP and a wash-out period (of 3 days) is required before performing them.
• Elderly patients are more susceptible to many of the adverse effects of ACUZYRT SYRUP, including antimuscarinic effects, sedation and hypotension.
• Pruritus and/or urticaria may occur when ACUZYRT SYRUP is stopped, even if those symptoms were not present before treatment initiation. The symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.
• Because of their antimuscarinic properties, antihistamines should be used with care in conditions such as closed-angle glaucoma, urinary retention, prostatic hyperplasia, or pyloroduodenal obstruction. Other adverse effects of antihistamines suggest caution in patients with epilepsy and severe cardiovascular disorders.
• Antihistamines do not have a place in the treatment of asthma.
• Some antihistamines have been associated with foetal abnormalities when taken during pregnancy, but a number of large studies have failed to demonstrate any strong associations.
• Special warnings about the excipients: ACUZYRT SYRUP contains sorbitol. Patients with the rare hereditary condition of sorbitol intolerance should not take ACUZYRT SYRUP. The preservatives methyl parahydroxybenzoate and propyl parahydroxybenzoate included in ACUZYRT SYRUP may cause allergic reactions (possibly delayed).

Concomitant use of alcohol and other sedating medicines should be avoided. Antihistamines may enhance the sedative effects of central nervous system depressants including alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives, and neuroleptics. MAOIu2019s may enhance the antimuscarinic effects of antihistamines, and antihistamines have an additive antimuscarinic action with other antimuscarinic drugs, such as atropine and tricyclic antidepressants. It has been suggested that antihistamines could mask the warning signs of damage caused by ototoxic drugs such as aminoglycoside antibiotics. Due to pharmacokinetic, pharmacodynamic and tolerance profile of cetirizine, no interactions are expected with this antihistamine. Actually, neither pharmacodynamic nor significant pharmacokinetic interaction was reported in drug-drug interactions studies performed, notably with pseudoephedrine or theophylline (400 mg/day). There is no evidence of an interaction between cetirizine and cimetidine, ketoconazole, erythromycin, azithromycin, diazepam, glipizide and pseudoephedrine. The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.

Pregnancy: The safety in pregnancy has not been established (see section 4.3).

Breastfeeding: ACUZYRT SYRUP is contraindicated in lactating women since the active ingredient is excreted in breast milk.

Fertility: Limited data is available on human fertility, but no safety concern has been identified. Animal data show no safety concern for human reproduction.

ACUZYRT SYRUP can lead to drowsiness and patients should be aware how they react to ACUZYRT SYRUP and exercise caution before driving, operating hazardous machinery or performing hazardous tasks.

b. Tabulated summary of adverse reactions

MedDRA system organ class Frequency Side effects

Psychiatric disorders Frequent Somnolence (may vary from slight drowsiness to deep sleep). Less frequent Agitation.

Nervous system disorders Frequent Dizziness, headache. Less frequent Paraesthesias. Frequency unknown In-coordination, nervousness. In high doses, CNS stimulation may be attributed to antimuscarinic activity. Extra-pyramidal symptoms have been reported.

Respiratory, thoracic and mediastinal disorders Frequent Pharyngitis, rhinitis. Less frequent Thickening of mucous, bronchospasm.

Gastrointestinal disorders Frequent Dry mouth, nausea. Less frequent Epigastric pain, diarrhoea. Frequency unknown Constipation, vomiting, increased appetite.

General disorders and administration site conditions Frequent Lassitude.

Ear and labyrinth disorders Less frequent Tinnitus.

Blood and lymphatic system disorders Less frequent Haemolytic anaemia, agranulocytosis, leucopenia, thrombocytopenia (these may have an immune basis.)

Skin and subcutaneous tissue disorders Less frequent Jaundice, hair loss, sweating, photosensitivity. Frequency unknown Skin reactions (rash), angioedema (with cross sensitivity to related medicines).

Vascular disorders Less frequent Hypotension.

c. Description of selected adverse reactions

Skin reactions occurring after discontinuation of ACUZYRT SYRUP: After discontinuation of ACUZYRT SYRUP, pruritis (intense itching) and/or urticaria have been reported (see section 4.4.)

d. Paediatric population

Children below 12 years of age

MedDRA system organ class Frequency Side effects

Gastro - intestinal disorders Frequent Diarrhoea.

Psychiatric disorders Frequent Somnolence. Less frequent Nightmares, hallucinations and convulsions. Frequency unknown Insomnia, nervousness, euphoria, irritability, tremors.

Respiratory, thoracic and mediastinal disorders Frequent Rhinitis.

General disorders and administration site conditions Frequent Fatigue.

Nervous system disorders Frequency unknown Paradoxical CNS stimulation.

Post-marketing data

MedDRA system organ class Frequency Side effects

Blood and lymphatic disorders Less frequent Thrombocytopenia.

Immune system disorders Less frequent Hypersensitivity, anaphylactic shock.

Metabolism and nutrition disorders Frequency unknown Increased appetite.

Psychiatric disorders Less frequent Agitation, aggression, confusion, depression, hallucination, insomnia, tics. Frequency unknown Suicidal ideation, nightmare.

Nervous system disorders Less frequent Paraesthesia, convulsions, dysgeusia, dyskinesia, dystonia, syncope, tremor. Frequency unknown Amnesia, memory impairment.

Eye disorders Less frequent Accommodation disorder, blurred vision, oculogyric crisis.

Ear and labyrinth disorders Frequency unknown Vertigo.

Cardiac disorders Less frequent Tachycardia.

Gastrointestinal disorders Less frequent Diarrhoea.

Hepatobiliary disorders Less frequent Abnormal hepatic function (increased transaminases, alkaline phosphatase, u03b3-GT and bilirubin). Frequency unknown Hepatitis.

Skin and subcutaneous tissue disorders Less frequent Pruritus, rash, urticaria, angioneurotic oedema, fixed drug eruption. Frequency unknown Acute generalized exanthematous pustulosis.

Musculoskeletal and connective tissue disorders Frequency Unknown Myalgia, arthralgia.

Renal and urinary disorders Less frequent Dysuria, enuresis. Frequency unknown Urinary retention.

General disorders and administration site conditions Less frequent Asthenia, malaise, oedema.

Investigations Less frequent Weight increased.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 or to Cipla Medpro (Pty) Ltd. by email: [email protected] or telephone: 080 222 6662 (toll free).

Symptoms

Symptoms observed after an overdose of cetirizine, as in ACUZYRT SYRUP, are mainly associated with CNS effects or with effects that could suggest an anticholinergic effect. Drowsiness is an expected symptom of overdosage. Overdosage may produce agitation, confusion, diarrhoea, dizziness, headache, malaise, mydriasis, restlessness, sedation, somnolence, stupor, pruritus, rash, urinary retention, fatigue, tremor and tachycardia. Overdosage may be fatal especially in infants and children. In infants and children, central nervous system stimulation predominates over central nervous system depression, causing ataxia, excitement, tremors, psychoses, hallucinations and convulsions; hyperpyrexia may also occur. Deepening coma and cardiorespiratory collapse may follow. In adults, central nervous system depression is more common with drowsiness, coma and convulsions, progressing to respiratory failure or possible cardiovascular collapse.

Management

There is no specific antidote. Cetirizine is not effectively removed by dialysis. Treatment is symptomatic and supportive.