Calcium-channel blockers (class III calcium antagonists).

Diltiazem - angina

ADIZEM-XL capsules 120 mg have a pale pink body and a navy blue cap, marked DCR 120. ADIZEM-XL capsules 180 mg have a dark pink body and a royal blue cap marked DCR 180. ADIZEM-XL capsules 200 mg have a brown body and a brown cap marked DCR 200. ADIZEM-XL capsules 240 mg have a dark red body and a blue cap marked DCR 240. ADIZEM-XL capsules 300 mg have a dark maroon body and a pale blue cap marked DCR 300.

Prolonged release capsules. ADIZEM-XL capsules 120 mg have a pale pink body and a navy blue cap, marked DCR 120. ADIZEM-XL capsules 180 mg have a dark pink body and a royal blue cap marked DCR 180. ADIZEM-XL capsules 200 mg have a brown body and a brown cap marked DCR 200. ADIZEM-XL capsules 240 mg have a dark red body and a blue cap marked DCR 240. ADIZEM-XL capsules 300 mg have a dark maroon body and a pale blue cap marked DCR 300.

Management of angina pectoris. Treatment of mild to moderate hypertension.

Route of administration

Oral

Posology

Dosage requirements may differ between patients with angina and patients with hypertension. In addition, individual patients' responses may vary necessitating careful titration. This range of capsule strengths facilitates titration to the optimal dose.

The capsules should be swallowed whole and not chewed.

Adults:

For patients new to diltiazem therapy the usual starting dose is one 240 mg capsule daily.

Patients currently receiving a total daily dose of 180 mg diltiazem (as 90 mg b.d. or 60 mg t.i.d.) and transferring to ADIZEM-XL capsules should be given the 240 mg capsule (o.d.). A patient receiving 240 mg/day of diltiazem (as 120 mg b.d.) should commence treatment on the 240 mg capsule (o.d.), titrating to the 300 mg capsule (o.d.) if required.

ADIZEM-XL capsules are not recommended for children. Safety and efficacy in children have not been established.

In order to avoid confusion, it is suggested that patients, once titrated to an effective dose using ADIZEM-XL capsules, should remain on this treatment and should not be changed between different presentations.

ADIZEM-XL capsules should not be taken at the same time as an alcoholic beverage (refer to Section 4.5, Interactions with other Medicinal Products and Other Forms of Interaction).

For patients new to diltiazem therapy, the usual starting dose is one 120 mg capsule daily. If necessary the dose may be gradually increased but careful monitoring of this group of patients is advised.

Elderly patients transferring to ADIZEM-XL capsules should receive the same total daily dose of diltiazem, titrating upwards as required.

Pregnancy and in women of child bearing capacity. Patients with bradycardia (less than 50 bpm), second or third degree heart block, sick sinus syndrome, decompensated cardiac failure, patients with left ventricular dysfunction following myocardial infarction. Concurrent use with dantrolene infusion because of the risk of ventricular fibrillation.

Route of administration

Oral

Posology

Dosage requirements may differ between patients with angina and patients with hypertension. In addition, individual patients' responses may vary necessitating careful titration. This range of capsule strengths facilitates titration to the optimal dose.

The capsules should be swallowed whole and not chewed.

Adults:

For patients new to diltiazem therapy the usual starting dose is one 240 mg capsule daily.

Patients currently receiving a total daily dose of 180 mg diltiazem (as 90 mg b.d. or 60 mg t.i.d.) and transferring to ADIZEM-XL capsules should be given the 240 mg capsule (o.d.). A patient receiving 240 mg/day of diltiazem (as 120 mg b.d.) should commence treatment on the 240 mg capsule (o.d.), titrating to the 300 mg capsule (o.d.) if required.

Elderly and patients with impaired hepatic and renal function:

For patients new to diltiazem therapy, the usual starting dose is one 120 mg capsule daily. If necessary the dose may be gradually increased but careful monitoring of this group of patients is advised.

Elderly patients transferring to ADIZEM-XL capsules should receive the same total daily dose of diltiazem, titrating upwards as required.

Due consideration should be given to the possibility of an additive effect when diltiazem is prescribed with drugs which may induce bradycardia or other anti-arrhythmic drugs.

Diltiazem hydrochloride has been used safely in combination with beta-blockers, diuretics, ACE-inhibitors and other anti-hypertensive agents. It is recommended that patients receiving these combinations should be regularly monitored. Concomitant use with alpha-blockers such as prazosin should be strictly monitored because of the possible synergistic hypotensive effect of this combination. Patients with pre-existing conduction defects should not receive the combination of diltiazem and beta-blockers.

Case reports have suggested that blood levels of carbamazepine, cyclosporin and theophylline may be increased when given concurrently with diltiazem hydrochloride. Care should be exercised in patients taking these drugs. In common with other calcium antagonists diltiazem hydrochloride may cause small increases in plasma levels of digoxin.

Concurrent use with H₂ -antagonists may increase serum levels of diltiazem.

Treatment with diltiazem has been continued without problem during anaesthesia, but the anaesthetist should be made aware of the treatment regimen.

ADIZEM-XL capsules should not be taken at the same time as alcohol, as it may increase the rate of release of diltiazem from the prolonged release preparation. In addition, the combination of alcohol and diltiazem may have an additive vasodilatory effect.

Diltiazem is generally well tolerated. Occasional undesirable effects:

• nausea
• headache
• oedema of the legs
• flushing
• hypotension
• fatigue
• gastrointestinal disturbance
• gingival hyperplasia which disappear on cessation of treatment.

Serious skin reactions such as exfoliative dermatitis and allergic skin reactions, such as angioneurotic oedema, erythema multiforme and vasculitis have been reported.

Diltiazem may cause depression of atrioventricular nodal conduction and bradycardia. Isolated cases of moderate and transient increased liver transaminases have been observed at the start of treatment. Isolated cases of clinical hepatitis have been reported, which resolved when diltiazem was withdrawn.

Napp

(POM)

04 June 2009