Retersic 10 10,0 mg CAPSULE

Allergic processes responding to a histamine H 1 -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: One 10 mg soft capsule daily.

Paediatric population

Children 6 to 12 years old: One 10 mg soft capsule daily.

The use of RETERSIC is not recommended in children less than 6 years since this formulation does not allow for appropriate dose adaptation.

• Hypersensitivity to cetirizine, hydroxyzine, any piperazine or to any of the excipients of RETERSIC (see section 6.1).
• Patients with severe renal impairment at less than 30 ml/min creatinine clearance.
• Pregnancy and lactation since safety has not been established during pregnancy and cetirizine is excreted in breastmilk. (see section 4.6).
• In children under 2 years of age.
• The use of RETERSIC is not recommended in children less than 6 years since this formulation does not allow for appropriate dose adaptation.

Avoid alcohol consumption.

Caution in epileptic patients and patients at risk of convulsions is recommended.

General

Severe skin reactions such as acute generalised exanthematous pustulosis (AGEP) have been reported with cetirizine-containing products. This acute pustular eruption may exhibit an early or delayed onset with numerous small, mostly non-follicular pustules arising on a widespread edematous erythema mainly localised on the skin folds, trunk, and upper extremities, which may be accompanied by fever. Patients should be carefully monitored. If symptoms persist or worsen, or if new symptoms occur, the patient should discontinue use and consult a doctor.

Studies have shown no effect of cetirizine hydrochloride on cognitive function, motor performance or sleep latency in healthy volunteers. However, in clinical trials the appearance of some CNS effects, particularly somnolence, have been observed. If drowsiness occurs, patients should be advised not to drive or operate machinery and to avoid concurrent use of RETERSIC with sedating substances because additional reductions in alertness and additional impairment of CNS performance may occur (see section 4.8).

Caution should be taken in patients with predisposition factors of urinary retention (e.g., spinal cord lesion, prostatic hyperplasia) as cetirizine as in RETERSIC may increase the risk of urinary retention.

Pruritus and/or urticaria may occur when cetirizine as in RETERSIC is stopped, even if those symptoms were not present before treatment initiation. In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.

Occasional instances of liver function test (transaminase) elevations have occurred during RETERSIC therapy. This incidence was 1.6% in the short-term trials and 4.4% in the 6-month trials. These liver enzyme elevations, mainly ALT, were generally reversible. There was no evidence of jaundice or hepatitis, and the clinical significance is presently unknown. Consequently, RETERSIC should be used with caution in patients with pre-existing liver disease.

Special populations:

Pregnant Women: RETERSIC should not be used during pregnancy (see section 4.6).

Use in asthmatics: RETERSIC has been safely administered to patients with mild to moderate asthma. RETERSIC did not cause exacerbation of asthma symptoms.

Paediatric population: RETERSIC should not be administered to children below 2 years of age (see section 4.2).

Elderly: RETERSIC was well tolerated by patients aged 65 and over. Clearance of RETERSIC is reduced in proportion to creatinine clearance.

To date there are no known interactions between cetirizine with other medicines. Studies with diazepam, glipizide, pseudoephedrine, antipyrine, ketoconazole, azithromycin, erythromycin and cimetidine have revealed no evidence of pharmacokinetic interactions.

No clinically significant interactions have been found with theophylline and cimetidine. Epidemiologic data suggests that there also would not be interaction with other macrolide antibiotics or imidazole antifungals. In clinical trials, cetirizine hydrochloride has been safely administered with beta-agonists, non-steroidal anti-inflammatory drugs, oral contraceptives, narcotic analgesics, corticosteroids, H 2 -antagonists, cephalosporins, penicillins, thyroid hormones and thiazide diuretics.

Allergy skin tests are inhibited by antihistamines such as RETERSIC and a wash-out period of 3 days is recommended before performing them.

RETTERSIC is contra-indicated in pregnancy and lactation (see section 4.3).

Patients should be warned that some individuals may experience sedation. It is therefore advisable to determine individual response before driving or performing complicated tasks. This effect may be compounded by simultaneous intake of alcohol or other central nervous system depressant. If drowsiness occurs, patients should be advised not to drive or operate machinery and to avoid concurrent use of RETERSIC with sedating substances because additional reductions in alertness and additional impairment of CNS performance may occur (see section 4.4).

a. Summary of the safety profile

RETTERSIC has potential adverse effects on the CNS, including somnolence, fatigue, dizziness and headache. In some cases, paradoxical CNS stimulations has been reported.

RETTERSIC is a selective antagonist of peripheral H 3 ,-receptors and is relatively free of anticholinergic activity. Cases of micturition difficulty, eye accommodation disorders and dry mouth have been reported. Instances of abnormal hepatic function with elevated hepatic enzymes accompanied by elevated bilirubin have been reported.

b. Tabulated summary of adverse reactions

MedDRA system organ class Frequency Adverse reactions

Blood and lymphatic disorders Frequency unknown Thrombocytopenia

Immune system disorders Frequency unknown Hypersensitivity, anaphylactic shock

Metabolism and nutrition disorders Frequency unknown Increased appetite

Psychiatric disorders Frequent Somnolence

Frequency unknown Agitation, aggression, confusion, depression, hallucination, insomnia, tics, suicidal ideation, nightmare

Nervous system disorders Frequent Headache, dizziness

Frequency unknown Paraesthesia, convulsions, dysgeusia, dyskinesia, dystonia, syncope, tremor, amnesia, memory impairment

Eye disorders Frequency unknown Accommodation disorder, blurred vision, oculogyration

Ear and labyrinth disorder Frequency Vertigo

MedDRA system organ class Frequency Adverse reactions

unknown Cardiac disorders Frequency unknown Tachycardia

Respiratory, thoracic and mediastinal disorders Frequent Pharyngitis, rhinitis

Gastrointestinal disorders Frequent Dry mouth, nausea, diarrhoea

Less frequent Abdominal pain

Hepatobiliary disorders Frequency unknown Hepatic function abnormal (increased transaminases, alkaline phosphatase, y-GT and bilirubin)

Skin and subcutaneous tissue disorders Frequency unknown Pruritus, rash, urticaria, angioneurotic oedema, fixed drug eruption

Musculoskeletal and connective tissue disorders Frequency unknown Arthralgia

Renal and urinary disorders Frequency unknown Dysuria, enuresis, urinary retention

General disorders and administration site conditions Frequent Fatigue

Frequency unknown Asthenia, malaise, oedema

Investigations Frequency unknown Weight Increased.

c. Description of selected adverse reactions

After discontinuation of cetirizine, pruritus (intense itching) and/or urticaria have been reported.

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 The applicant can be reached at the following contact number: 010 045 2500.

Symptoms: Symptoms observed after an overdose of RETERSIC are mainly associated with CNS effects or with effects that suggest an anticholinergic effect. Adverse events reported after an intake of at least 5 times the recommended daily dose is: confusion, diarrhoea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, restlessness, sedation, somnolence, stupor, tachycardia, tremor and urinary retention.

Management: There is no known specific antidote to RETERSIC. Should overdose occur, symptomatic or supportive treatment is recommended. Cetirizine is not effectively removed by dialysis.