Calcium-channel blockers (class III calcium antagonists).

Diltiazem - angina

Diltiazem hydrochloride 90 mg Diltiazem hydrochloride 120 mg Diltiazem hydrochloride 180 mg Diltiazem hydrochloride 240 mg Diltiazem hydrochloride 300 mg

Modified-release hard capsules

For the management of angina pectoris. For the management of mild to moderate hypertension.

Route of administration:

Oral use

Dosage recommendations:

Individual patients' responses to diltiazem may vary, necessitating careful titration.

The capsules should be swallowed whole and not chewed. Dosage may be taken with or without food.

Adults: The usual initial dose is 90 mg twice daily. Dosage may be increased gradually to 120 mg twice daily or 180 mg twice daily if required.

Patients currently receiving a total daily dose of 180 mg diltiazem (as 90 mg bd), may be titrated up to 240 mg (od). A patient receiving 240 mg per day of diltiazem (as 120 mg bd), should commence treatment on the 240 mg capsule (od), titrating to the 300 mg capsule (od), if required.

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

Diltiazem preparations are not recommended for children. Safety and efficacy in children has not been established.

Elderly and patients with renal and hepatic dysfunction: The starting dose should be 60 mg diltiazem twice daily. If necessary, the dose may be increased gradually but careful monitoring of this group of patients is advised. Where the patient is currently prescribed 120 mg this dose may, by careful titration, be increased to 240 mg od.

- Hypersensitivity to diltiazem or any of the ingredients

- 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.

Renal impairment, reduced left  Renal impairment, reduced left ventricular function, diabetes, acute porphyria. Monitor patients with mild bradycardia, 1st degree AV block or prolonged P-R 2 interval.

The use of diltiazem with other anti-arrhythmic drugs is not generally recommended.

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. Clinical and ECG monitoring may be required. Amiodarone and digoxin have an increased risk of bradycardia in combination with diltiazem, particularly in the elderly or at high dose.

Diltiazem hydrochloride has been used safely in combination with beta-blockers, diuretics, ACE-inhibitors and other antihypertensive 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. Concomittant use with beta-blockers requires close clinical and ECG monitoring, particularly at the start of treatment, as rhythm disturbances, conduction disturbances and heart failure are possible.

Patients with pre-existing conduction defects should not receive the combination of diltiazem and beta-blockers.

Combination with nitrates may produce additive vasodilation leading to hypotensive effects and faintness. Concomitant nitrates should be titrated to dose.

Case reports have suggested that blood levels of carbamazepine, ciclosporin 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. The risk of neurotoxicity with lithium is increased when co-administered with diltiazem.

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

Rifampicin may decrease plasma levels of diltiazem. The patient should be monitored when initiating or discounting rifampicin therapy.

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

Diltiazem treatment can raise the plasma levels of drugs exclusively metabolised by CYP 3A4, with a possible increase in risk of adverse reactions (for example, muscle disorders with statins)

Diltiazem is generally well tolerated. Occasional undesirable effects are nausea, gastrointestinal disturbances, gingival hyperplasia, headache, allergic skin reactions (including erythema multiforme, exfoliative dermatitis and rarely Stevens Johnsons syndrome) with or without fever, photosensitivity and vasculitis have been reported, oedema of the legs, flushing, hypotension and fatigue which disappear on cessation of treatment. Diltiazem may cause depression of atrioventricular nodal conduction and bradycardia and palpitations. Changes in liver function tests (with some isolated cases of clinical hepatitis, resolving on diltiazem withdrawal) and renal function have been reported in a few cases.

In common with other calcium channel blockers, exceptional cases of gynaecomastia and of extrapyramidal symptoms have occured. These resolved upon withdrawal of calcium agonists.

Chiesi Limited

(POM)

04 June 2009