MEZATIL

Posology Adult For all indications the usual initial dose is 90mg twice daily. Depending on clinical response, the patient’s dosage may be increased to 180mg twice daily if required. Elderly and patients with impaired hepatic or renal function Dosage should commence at the lower level of 60mg twice daily and be increased slowly in order to achieve the required level of control.

The daily dose should not exceed 90mg twice daily. Do not increase the dose if the heart rate falls below 50 beats per minute. Paediatric population Not recommended. Method of administration The method of administration is by oral use.

To be swallowed whole, not chewed.

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, lymphadenopathy, Eosinophilia Psychiatric disorders Nervousness, insomnia Mood changes (including depression), hallucination, personality change, Nervous system disorders Headache, dizziness Extrapyramidal syndrome, syncope, amnesia, paraesthesia, somnolence, tremor Very common Common Uncommon Rare Not known Cardiac disorders Atrioventricular block (may be of first, second or third degree; bundle branch block may occur), palpitations Bradycardia Sinoatrial block, congestive heart failure, angina, arrhythmia, congestive heart failure, palpitations Vascular disorders Flushing Orthostatic hypotension Vasculitis (including leukocytoclastic vasculitis), hypotension Gastrointestinal disorders Constipation, dyspepsia, gastric pain, nausea Vomiting, diarrhea Dry mouth Gingival hyperplasia, anorexia, gingivitis, gingival hypertrophy 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 Steven-Johnson's syndrome and toxic epidermal necrolysis), sweating, exfoliative dermatitis, acute generalized exanthematous pustulosis, occasionally desquamative erythema with or without fever, petechiae, pruritus, Lupus-like syndrome.

Very common Common Uncommon Rare Not known Reproductive system and breast disorders Gynecomastia, sexual dysfunction General disorders and administration site conditions Peripheral oedema Malaise Gait abnormality Investigations Weight increase, CK elevation, Eye disorder Amblyopia Ear and labyrinth disorders Tinnitus Respiratory, thoracic and mediastinal disorders Dyspnoea, epistaxis, nasal congestion Metabolism and nutrition disorders Hyperglycemia Renal and urinary disorders Nocturia, polyuria Musculoskeletal and connective tissue disorders Osteoarticular pain, muscle pain In studies carried out to date, serious adverse reactions with diltiazem have been rare; however, it should be recognised that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies.

Rare instances of hyperglycaemia have been reported in association with diltiazem hydrochloride. The use of diltiazem hydrochloride in diabetic patients may require adjustment of their control. The product should be used with caution in patients with hepatic dysfunction or with impaired renal function.

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.

Abnormalities of liver function have been received, these reactions have been reversible upon discontinuation of therapy. Closed observation is necessary in patients with reduced left ventricular function. bradycardia (risk of exacerbation) or with, 1st degree atrio-ventricular block or prolonged PR interval detected on the electrocardiogram (risk of exacerbation and rarely, of complete block).

Cases of acute renal failure secondary to decreased renal perfusion have been reported in patients with existing cardiac disease especially reduced left ventricular function, severe bradycardia or severe hypotension. Careful monitoring of renal function is advised.

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.

Do not suck or chew capsules. Patients with rare hereditary problems of fructose intolerance, glucosegalactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. As with any drug given over prolonged periods, laboratory parameters should be monitored at regular intervals.

Calcium channel blocking agents, such as diltiazem, may be associated with mood changes, including depression. 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.

6 ) • In women of child bearing potential who are not using effective contraception. 6). • In patients with severe bradycardia (less than 40 beats per minute), second or third degree heart block or sick sinus syndrome except in the presence of a functioning ventricular pacemaker.

• In patients with cardiac failure after myocardial infarction; left ventricular failure with stasis or with pulmonary congestion. • Severe aortic stenosis • Cardiogenic shock • Severe hypotension (systolic blood pressure less than 90mmHg) • Concomitant administration of dantrolene infusion.

5). 5). Additionally, for the intravenous forms, patients known to have an accessory bypass (Wolf-Parkinson-White syndrome or short PR syndrome), and who develop atrial fibrillation or flutter, should not be administered intravenous diltiazem.