Zemtard® XL

Prescribing Information

Adverse events should be reported.
Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/.
Adverse events should also be reported to Galen Limited on 028 3833 4974 and select the customer services option, or e-mail customer.services@galen-pharma.com.
Medical information enquiries should also be directed to Galen Limited.

Zemtard® XL Prescribing Information
Please refer to the Summary of Product Characteristics (SPC) before prescribing Zemtard XL.
Presentation: Hard gelatin capsules containing prolonged release diltiazem hydrochloride beads for oral use. Zemtard 120 XL: Brownish-red and orange capsules marked “DIL 120”, each containing 120mg diltiazem hydrochloride. Zemtard 180 XL: Pink and grey capsules marked “DIL 180”, each containing 180mg diltiazem hydrochloride. Zemtard 240 XL: Light blue capsules marked “DIL 240”, each containing 240mg diltiazem hydrochloride. Zemtard 300 XL: Light blue and white capsules marked “DIL 300”, each containing 300mg diltiazem hydrochloride. Indications: Treatment of mild to moderate hypertension. Prophylaxis and treatment of angina pectoris. Dosage and administration: Capsules should be swallowed whole (not chewed) with half a glass of fluid. Adults: The recommended dose is between 180 and 300mg given once daily. Doses of up to 360mg/day in hypertension and 480mg/day in angina may be of benefit in some patients. Elderly and patients with impaired renal or hepatic function: Recommended starting dose of 120mg daily. The dose should not be increased if the heart rate falls below 50bpm. Children: Not recommended. Contraindications: Hypersensitivity to diltiazem or any of the excipients; severe bradycardia (below 40 bpm); in sick sinus syndrome or in second- or third-degree AV block, except in the presence of a functioning ventricular pacemaker; in left ventricular failure with pulmonary congestion; diltiazem should not be given concomitantly with dantrolene infusion; in combination with ivabradine; pregnancy; in women of childbearing potential not using effective contraception and while breastfeeding. Warnings and Precautions: Close observation is necessary in patients with heart failure or reduced left ventricular function, bradycardia (risk of exacerbation), or with first-degree AV block detected on ECG (risk of exacerbation and rarely, of complete block), prolonged PR interval. Prior to general anaesthesia, the anaesthetist must be informed of ongoing diltiazem treatment. Depression of cardiac contractility, conductivity and automaticity, as well as vascular dilatation associated with anaesthetics may be potentiated by calcium channel blockers. Treatment should commence with reduced doses in elderly patients and in patients with impaired liver or kidney function (possible increase of plasma concentrations). The contraindications and precautions should be closely observed and close monitoring, particularly of heart rate, should be carried out at the beginning of treatment. Sudden withdrawal of diltiazem might be associated with an exacerbation of angina. Calcium channel blockers, such as diltiazem, may be associated with mood changes, including depression. Early recognition of symptoms is important, especially in predisposed patients (drug discontinuation should be considered). Use with caution in patients at risk of developing an intestinal obstruction. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. Interactions: Concomitant use contraindicated: Dantrolene (infusion), ivabradine. Concomitant use requiring caution: Lithium, nitrate derivatives (prescription of nitrate derivatives should only be carried out at gradually increasing doses), theophylline, alpha-antagonists (combination should be considered only with strict monitoring of blood pressure), amiodarone and digoxin (particularly in elderly and with high doses), beta-blockers (combination must only be used under close clinical and ECG monitoring, particularly at the beginning of treatment), other antiarrhythmic agents (concomitant use is not recommended, combination should only be used under close clinical and ECG monitoring), carbamazepine (plasma carbamazepine concentrations should be assayed and dose adjusted if necessary), phenytoin, primidone, rifampicin (patient should be carefully monitored when initiating or discontinuing rifampicin treatment), cimetidine and ranitidine (patients currently receiving diltiazem therapy should be carefully monitored when initiating or discontinuing therapy with anti-H2 agents, an adjustment in diltiazem daily dose may be necessary), immunosuppressants: ciclosporin (it is recommended that the ciclosporin dose be reduced, renal function monitored, circulating ciclosporin levels assayed and that the dose should be adjusted during combined therapy and after its discontinuation), sirolimus, tacrolimus and everolimus; atazanavir (reduce dose of diltiazem), ritonavir; barbiturates, cilostazol (avoid concomitant use). General information to be taken into account: Caution and careful titration are necessary in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction e.g. other calcium channel blockers and anti-hypertensive drugs. Plasma concentration of both drugs may increase when diltiazem is given with nifedipine. Diltiazem is metabolized by CYP3A4. A moderate increase of diltiazem plasma concentration in co-administration with a stronger CYP3A4 inhibitor has been documented. Diltiazem is also a CYP3A4 inhibitor. Co-administration with other CYP3A4 substrates may result in an increase in plasma concentration of either drug. Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations. Midazolam, triazolam (special care should be taken when prescribing short-acting benzodiazepines metabolised by CYP3A4 in patients using diltiazem); anxiolytics and hypnotics, corticosteroids (patient should be monitored when initiating methylprednisolone treatment, adjustment of methylprednisolone dose may be necessary); atorvastatin, simvastatin and lovastatin (when possible, a non CYP3A4-metabolised statin should be used together with diltiazem, otherwise close monitoring for signs and symptoms of a potential statin toxicity is required). Other interactions: General anaesthetics, imipramine and possibly other tricyclic antidepressants, MAOIs; itraconazole, mefloquine. Refer to SmPC for full details on interactions. Fertility, pregnancy and lactation: Diltiazem has been shown to have reproductive toxicity in certain animal species (rat, mice, rabbit). In the absence of adequate evidence of safety in human pregnancy, diltiazem should not be used in pregnancy or in women of childbearing potential not using effective contraception. Breastfeeding while taking this drug should be avoided. If use of the drug is considered essential in nursing mothers, an alternative method of feeding should be instituted, since diltiazem is excreted in breast milk at low concentrations. Effects on ability to drive and use machines: On the basis of reported adverse drug reactions i.e. dizziness, malaise and hypotension, the ability to drive and use machines could be altered. However, no studies have been performed. Patients should be warned not to drive or operate machinery until the effect of diltiazem has been established. Undesirable effects: Very common (≥1/10): Peripheral oedema; Common (≥1/100 to <1/10): Headache, dizziness, atrioventricular block (may be of first, second or third degree; bundle branch block may occur), palpitations, flushing, constipation, dyspepsia, gastric pain, nausea, erythema, malaise; Uncommon (≥1/1,000 to ≤1/100): Nervousness, insomnia, bradycardia, orthostatic hypotension, anorexia, vomiting, diarrhoea, taste disturbance, weight gain, hepatic enzymes increase (AST, ALT, LDH, ALP); Rare (≥1/10,000 to ≤1/1,000): Dry mouth, urticaria; Not known (cannot be estimated from the available data): Thrombocytopenia, mood changes (including depression), extrapyramidal syndrome, sinoatrial block, congestive heart failure, vasculitis (including leukocytoclastic vasculitis), gingival hyperplasia, hepatitis, photosensitivity (including lichenoid keratosis at sun exposed skin areas), photodistributed hyperpigmentation, angioneurotic oedema, rash, erythema multiforme (including Steven-Johnson's syndrome and toxic epidermal necrolysis), sweating, exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), occasionally desquamative erythema with or without fever, gynecomastia, asthenia/fatigue. Overdose: Please refer to SmPC. Basic NHS cost: Blister packs of 28 capsules. Zemtard 120mg XL: £6.10. Zemtard 180mg XL: £6.20. Zemtard 240 XL: £6.30. Zemtard 300 XL: £6.70. Legal classification: POM. MA Number: Zemtard 120 XL: PL 27827/0033. Zemtard 180 XL: PL 27827/0034. Zemtard 240 XL: PL 27827/0035. Zemtard 300 XL: PL 27827/0036. Full prescribing information available from the MA Holder: Galen Limited, Seagoe Industrial Estate, Craigavon, Northern Ireland, BT63 5UA. Date of Preparation: March 2018.