INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
Tilazem 60
Tilazem 90 BD
Tilazem 180 CR
Tilazem 240 CR

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

Tilazem 60
(tablet)
Tilazem 90 BD
(tablet)
Tilazem 180 CR
(controlled-release capsule)
Tilazem 240 CR
(controlled-release capsule)

COMPOSITION:
Each tablet contains:

Tilazem 60:	Diltiazem hydrochloride 60 mg
Tilazem 90 BD:	Diltiazem hydrochloride 90 mg

Each controlled-release capsule contains:

Tilazem 180 CR:	Diltiazem hydrochloride 180 mg
Tilazem 240 CR:	Diltiazem hydrochloride 240 mg

PHARMACOLOGICAL CLASSIFICATION:
A: 7.1 Vasodilators, hypotensive medicines.

PHARMACOLOGICAL ACTION:
Diltiazem is a calcium antagonist (calcium-channel blocker) that blocks the slow inward influx of calcium ions across membranes of cardiac muscle, and of smooth muscle in coronary and peripheral arteries.
By this means, diltiazem reduces myocardial oxygen demand, increases myocardial oxygen supply, and reduces blood pressure.
Pharmacokinetics
Diltiazem is subject to an extensive first-pass effect, giving an absolute bioavailability (compared to intravenous dosing) of about 40%. Diltiazem undergoes extensive hepatic metabolism; therefore, only 2% to 4% of the unchanged drug appears in the urine. In cases of serious liver damage, delayed biotransformation may be anticipated. In-vitro studies show that 70%-80% of diltiazem is bound to plasma proteins. Single oral doses of 30 to 120 mg result in detectable plasma levels within 30 to 60 minutes and peak plasma levels two to three hours after drug administration. The plasma elimination half-life following single or multiple drug administration is approximately 3,5 hours. Desacetyldiltiazem is also present in the plasma at levels of 10% to 20% of the parent drug and has 25% to 50% coronary vasodilatation activity of diltiazem.
There is a departure from dose-linearity when single doses of diltiazem above 60 mg are given; a 120 mg dose gave plasma levels three times that of the 60 mg dose.

INDICATIONS:
Prophylaxis of angina pectoris, including Prinzmetal's angina.
For the treatment of mild to moderate hypertension.

CONTRA-INDICATIONS:
Diltiazem should not be administered to patients known to be sensitive to diltiazem.
Since teratogenic effects were noted in animals, diltiazem should not be administered to pregnant women or to women of child-bearing age.
Diltiazem is excreted in human milk, and therefore should not be administered to lactating women.
Diltiazem should not be administered to patients with decompensated cardiac insufficiency, sick sinus syndrome, conduction disturbances (sino-atrial or atrio-ventricular block) and bradycardia (pulse rate less than 55/min).
Diltiazem should not be administered to patients with severe impairment of liver and kidney function.
It is not safe to administer diltiazem to patients suffering from porphyria.
Safety in children has not been established.

DOSAGE AND DIRECTIONS FOR USE:
Adults:
For the treatment of hypertension and angina.
The daily dosage for diltiazem ranges from 90 mg to 360 mg per day. The total daily dosage should be titrated upward from 90 mg per day to a maximum of 360 mg per day to meet the requirements of the individual patient. For daily dosages above 90 mg per day it may be possible to decrease the dosage after 2 - 3 months. Once the daily dosage has been optimised, the most appropriate preparation may be selected.
Tilazem 60:
30 - 60 mg three to four times a day.
If an acceptable clinical response has not been obtained, dosage may be increased by 30 - 60 mg increments given in three to four divided doses per day.
Tilazem 90 BD:
One to two 90 mg tablets twice a day.
Tilazem 90 BD tablets should be swallowed intact with some liquid. The dosage may be increased by 90 mg increments given in two divided doses per day.
Tilazem 180 CR:
One 180 mg capsule once daily or one 180 mg capsule twice daily.
The 180 CR capsules should be swallowed intact with some liquid.
Tilazem 240 CR:
One 240 mg capsule once daily.
The 240 CR capsule should be swallowed intact with some liquid.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Heartburn, gastric discomfort, nausea, dizziness, confusion, headache, erythema multiforme, ankle oedema, malaise, hypotension, bradycardia, first degree atrio-ventricular block, flushing and gynaecomastia have been reported. There have been reports of hyperactivity, sometimes with associated psychiatric symptoms.
Rash has been reported in association with diltiazem. These reactions are generally mild and resolve on cessation of therapy; however, erythema multiforme or exfoliative dermatitis has been reported less frequently. Isolated cases of clinical hepatitis have been reported which resolved on cessation of therapy.
The effects of vasodilation, particularly ankle oedema, are dose dependent and are more frequent in the elderly.
Transient increases in alkaline phosphatase, lactic dehydrogenase (LDH), SGOT and SGPT have been observed.
Tilazem administration should be stopped if signs of hypersensitivity are observed.
Precautions:
Tilazem should be administered with caution to elderly patients and patients with impairment of liver and kidney function. In these patients treatment should commence with reduced doses.
If bradycardia is noted, dosage should be decreased then discontinued if bradycardia persists.
Administer with caution to patients with pre-existing hypotension and also to those with impaired left ventricular function due to potential negative inotropic properties of diltiazem.
Interactions:
Patients receiving diltiazem in combination with diuretics, ACE-inhibitors and other antihypertensive agents should be regularly monitored. Concomitant use with alpha-blockers such as prazosin should be strictly monitored because of the possible marked synergistic hypotensive effect of this combination.
Tilazem should be administered with caution to patients taking beta receptor blocker agents or digitalis glycosides as these may have an additive effect on depression of AV conduction.
The combination of Tilazem with the beta-blocker propranolol may enhance the bioavailability of the propranolol significantly, and thus produce elevated levels of propranolol in the serum. Adjustment in the propranolol dosage may be warranted.
The combination of Tilazem with digitalis glycosides can inhibit digitalis glycoside metabolism and elevate serum levels which may cause digitalis glycoside toxicity.
Case reports have suggested that blood levels of carbamazepine, cyclosporin, and theophylline may be increased when given concurrently with diltiazem. Care should be exercised in patients taking these medicines.
Cimetidine's inhibition of the hepatic cytochrome P-450 system causes an increase in plasma diltiazem concentrations. An adjustment in the diltiazem dose may be warranted.
Patients who are taking diltiazem should inform the anaesthetist accordingly before receiving anaesthesia.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See side-effects.
Treatment is symptomatic and supportive. Further gastro-intestinal absorption can be limited by gastric lavage. Tilazem CR are extended-release capsules and effects may be slow in onset and prolonged.

IDENTIFICATION:

Tilazem 60:	White, square, flat-faced bevelled tablet, scored on one side, monogrammed Tilazem on opposite side.
Tilazem 90 BD:	White, ellipsoid tablet, scored on one side and monogrammed P-D 90 on other side.
Tilazem 180 CR:	White capsule imprinted 'D180' in black, containing off-white, roughly-spherical controlled-release beads.
Tilazem 240 CR:	White capsule imprinted 'D240' in black, containing off-white, roughly-spherical controlled-release beads.

PRESENTATION:

Tilazem 60:	Available in blisters (50 tablets) and securitainers (250 tablets).
Tilazem 90 BD:	Available in blisters (60 tablets).
Tilazem 180 CR:	Available in containers of 30 capsules.
Tilazem 240 CR:	Available in containers of 30 capsules.

STORAGE INSTRUCTIONS:
Store in a cool (below 25°C) dry place. Tilazem 60 and 90 BD to be protected from light and moisture. KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:

Tilazem 60:	Q/7.1/54
Tilazem 90 BD:	V/7.1/20
Tilazem 180 CR:	28/7.1/0579
Tilazem 240 CR:	28/7.1/0580

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pfizer Laboratories (Pty) Ltd
102 Rivonia Road
Sandton, 2196
South Africa

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
1 November 1994

ZIMBABWE DETAILS Tilazem 60: 89/12.6/2277        PP

Updated on this site: February 2005
Source: Pharmaceutical Industry
SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2005