HISMANAL-D® capsules.
SCHEDULING STATUS
Schedule 2.
PROPRIETARY NAME
(and dosage form)
HISMANAL-D® capsules.
COMPOSITION
Each capsule contains beads containing 240mg pseudoephedrine hydrochloride and one pellet containing 10mg of astemizole.
PHARMACOLOGICAL CLASSIFICATION
A.5.8 Preparations for the common cold including nasal decongestants and antihistaminics.
PHARMACOLOGICAL ACTION
HISMANAL-D is a combination of the histamine H1-receptor antagonist astemizole and of an extended-release formulation of the sympathomimetic pseudoephedrine hydrochloride.
HISMANAL-D combines the complementary pharmacological actions of astemizole, a long-acting selective antihistamine H1-receptor antagonist, with the nasal decongestant pseudoephedrine hydrochloride. The recommended dose of astemizole is 10mg once daily, and the extended-release formulation of 240mg pseudoephedrine also allows once-a-day dosing, so that HISMANAL-D can be administered once daily.
At steady state, the average peak plasma concentration of astemizole plus its metabolite desmethylastemizole (considered together to represent the pharmacologically active fraction in plasma) is 8ng/mL. There is extensive first-pass metabolism and significant tissue distribution. The terminal half-life is 24 hours for astemizole and 11days for desmethylastemizole. Average peak plasma concentration of pseudoephedrine is 438ng/mL; terminal half-life is 11hours.
Astemizole and pseudoephedrine given in combination do not interfere with each other’s bioavailability.
INDICATIONS
HISMANAL-D is indicated for the relief of all symptoms of allergic rhinitis (nasal hypersensitivity), such as nasal congestion (blocked nose), sneezing, rhinorrhoea (runny nose) and itchy eyes.
CONTRA-INDICATIONS
HISMANAL-D is contra-indicated in patients with known hypersensitivity to pseudoephedrine, other sympathomimetics, or astemizole, or to any of the inactive ingredients. Concomitant administration of ketoconazole with HISMANAL-D is contra-indicated.
Pseudoephedrine is contra-indicated in patients with severe hypertension, severe coronary artery disease and in patients receiving monoamine oxidase inhibitors.
The recommended daily dosage should not be exceeded. Since HISMANAL-D is extensively metabolized by the liver, the use of HISMANAL-D in patients with significant hepatic dysfunctions should generally be avoided.
Pregnancy and lactation.
DOSAGE AND DIRECTIONS FOR USE
Adults and children older then 12 years:
One capsule orally in the morning. The recommended dosage should not be exceeded.
This medication should not be continued for more then 3 weeks without consulting a doctor.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Patients known to have conditions leading to QT-prolongation may experience QT-prolongation and/or ventricular arrhythmias with astemizole. Therefore it is advisable to avoid its use in patients with a congenital QT-syndrome; in patients who are taking medications which are reported to prolong the QT-interval (including anti-arrhythmics, terfenadine and erythromycin); or in patients with uncorrected hypokalaemia. Pseudoephedrine should be used with caution in patients with hypertension, ischaemic heart disease, hyperthyroidism and diabetes mellitus, increased intra-ocular pressure or prostatic hypertrophy. Pseudoephedrine may produce central nervous stimulation with convulsions, or cardiovascular collapse with accompanying hypotension.
The most common adverse reactions reported in patients taking HISMANAL-D are headache, dry mouth, insomnia (sleeplessness). With astemizole alone, weight gain has been reported. Cases of hypersensitivity reactions such as angio-oedema, bronchospasm, photosensitivity, pruritus, rash and anaphylactoid reactions have been reported. There have also been isolated cases of convulsions, benign paraesthesias, myalgia/arthralgia, oedema, mood disturbance, insomnia, nightmares, transaminase elevations and hepatitis. In most cases, a causal relationship with HISMANAL-D is unclear.
Pseudoephedrine may produce ephedrine-like reactions, with symptoms of CNS-stimulation (eg. insomnia [sleeplessness], nervousness, convulsions [seizures]), cardiovascular stimulation (eg. tachycardia, palpitations, arrhythmias [increase in pulse, heart racing, irregular pulse]), headache, dizziness or nausea.
HISMANAL-D lacks significant sedative effects. Patients should, however, be warned that a small number of individuals may experience sedation. It is therefore advisable to determine individual response before driving or performing complicated tasks. This effect may be compounded by the simultaneous intake of alcohol or other central nervous system depressants.
Drug Interaction
HISMANAL-D should not be given to patients using monoamine oxidase [MAO] inhibitors (antidepressants). Care should be taken in administering pseudoephedrine concomitantly with other sympathomimetic amines and beta-adrenergic blockers, since these may increase the pressor effect of pseudoephedrine.
Pseudoephedrine may reduce the antihypertensive effects of antihypertensives interfering with sympathetic activity (eg. methyldopa, reserpine).
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Although overdoses have been reported with no ill effects, rare cases of serious life-threatening cardiovascular adverse events including QT-prolongation, torsades de pointes, and other ventricular arrhythmias have been observed in patients exceeding recommended doses of astemizole. While the majority of such events have occurred following substantial overdoses of astemizole, torsades de pointes (arrhythmias) have very rarely occurred at reported doses of 20 - 30mg daily (2 - 3 times the recommended daily dose).
In some cases, severe arrhythmias have been preceded by or associated with one or more episodes of syncope. Therefore, syncope in patients receiving astemizole should lead to immediate discontinuation of treatment and appropriate clinical eva luation, including electrocardiographic testing.
Overdosage with pseudoephedrine can cause excessive central-nervous system stimulation (eg. insomnia, nervousness, convulsions), or cardiovascular stimulation (eg. tachycardia, palpitations, arrhythmias). Other effects include hypertension, pallor, mydriasis, hyperglycaemia and urinary retention. In some individuals there may be central nervous system depression with somnolence, stupor, or respiratory depression. In the event of overdosage, supportive measures including emesis or gastric lavage should be employed. Astemizole does not appear to be dialysable. The elimination of pseudoephedrine can be accelerated by acid diuresis or dialysis. In these patients the ECG should be carefully monitored. If the QT interval is prolonged, the monitoring should continue as long as it remains prolonged. Appropriate anti-arrhythmic treatment may be needed, but treatment with anti-arrhythmics known to prolong QT-interval should be avoided.
IDENTIFICATION
Capsules with a light blue body and a light green cap.
PRESENTATION
Cartons containing one or more blister packs of 5 or 7 or 10 capsules each.
STORAGE INSTRUCTIONS
Store below 25°C, in a dry place. Protect from light.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER
Y/5.8/409
NAME AND BUSINESS ADDRESS OF THE APPLICANT
JANSSEN
PHARMACEUTICA
Janssen Pharmaceutica (Pty) Ltd.,
(Reg. No. 80/11122/07)
15th Road, HALFWAY HOUSE, 1685
DATE OF PUBLICATION OF THIS PACKAGE INSERT
4 December 1992.
© JPh (Pty) Ltd. SA 1993
® Trademark |
