DILTIAZEM HYDROCHLORIDE

Adults The usual maintenance dose is one tablet (60 mg) three times daily. As patient response may vary, the dose can be increased to a maximum of 360 mg daily in divided doses. Higher doses up to 480 mg/day have been used with benefit in some patients especially in unstable angina.

There is no evidence of any decrease in efficacy at these high doses. Diltiazem has not been reported to precipitate angina.

Elderly and patients with impaired renal function:

Initially 60 mg twice daily. Monitoring of the heart rate should be carried out. In patients suffering from liver problems, periodical checks of liver function are recommended during treatment with these tablets.

Children:

Not recommended Route of administration: Oral

The following CIOMS frequency rating is used, when applicable:

Very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to 1/100); rare (1/10,000 to 1/1,000); very rare (1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

Very common common Uncommon Rare Not known Blood and lymphatic system disorders Thrombocytopenia Psychiatric disorders Nervousness, insomnia Mood changes (including depression) Nervous system disorders Headache, dizziness Extrapyramidal syndrome Cardiac disorders Atrioventricular block (may be of first, second or third degree, bundle branch block may occur), palpitations Bradycardia Sinoartrial block, congestive heart failure, sinus arrest, cardiac arrest (asystole) Vascular disorders Flushing Orthostatic hypotension Vasculitis (including leukocytoclastic vasculitis) Gastrointestinal disorders Constipation, dyspepsia, gastric pain, nausea Vomiting, diarrhoea Dry mouth Gingival hyperplasia Metabolism and nutrition disorders Hyperglycemia Hepatobiliary disorders Hepatic enzymes increase (AST, ALT, LDH, ALP increase) Hepatitis Skin and subcutaneous tissue disorders Erythema Urticaria Photosensitivity (including lichenoid keratosis at sun exposed skin areas), angioneurotic oedema, rash, erythema multiforme (including StevenJohnson’s syndrome and toxic epidermal necrolysis), sweating, exfoliative dermatitis, acute generalized exanthematous pustulosis, occasionally desquamative erythema with or without fever Reproductive system and breast disorders Gynecomastia General disorders and administration site conditions Peripheral oedema Malaise Respiratory, thoracic and mediastinal disorders Bronchospasm (including asthma aggravation) The current literature suggests that the effects of vasodilation particularly ankle oedema are dose dependent and are more frequent in the elderly.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine. Close observation is necessary in patients with reduced left ventricular function, bradycardia (risk of exacerbation) prolonged PR interval, or with a first degree AV block detected on the electrocardiogram (risk of exacerbation and rarely, of complete block).

Prior to general anaesthesia, the anaesthesist must be informed of ongoing diltiazem treatment. Depression of cardiac contractility, conductivity and automaticity, as well as the vascular dilatation associated with anaesthetics may be potentiated by calcium channel blockers.

Increase of plasma concentrations of diltiazem may be observed in the elderly and in patients with renal or hepatic insufficiency. The contraindications and precautions should be carefully observed and close monitoring, particularly of heart rate, should be carried out at the beginning of treatment.

Calcium channel blocking agents, such as diltiazem, may be associated with mood changes, including depression. Early recognition of relevant symptoms is important, especially in predisposed patients. In such cases, drug discontinuation should be considered.

Like other calcium channel antagonists, diltiazem has an inhibitory effect on intestinal motility. Therefore it should be used with caution in patients at risk to develop an intestinal obstruction. Careful monitoring is necessary in patients with latent or manifest diabetes mellitus due to a possible increase in blood glucose.

Tablet residues from slow release formulations of the product may pass into the patient's stools; however, this finding has no clinical relevance. The use of diltiazem may induce bronchospasm, including asthma aggravation, especially in patients with preexisting bronchial hyper-reactivity.

5). • Combination with ivabradine • Concurrent use with lomitapide • Concurrent use with asunaprevir