INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo APO-ISOSORBIDE DINITRATE 10 mg (tablets)
APO-ISOSORBIDE DINITRATE 30 mg (tablets)

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

APO-ISOSORBIDE DINITRATE 10 mg (tablets)
APO-ISOSORBIDE DINITRATE 30 mg (tablets)

COMPOSITION:
APO-ISOSORBIDE DINITRATE 10 mg: Each tablet contains
Isosorbide dinitrate 10 mg.
APO-ISOSORBIDE DINITRATE 30 mg: Each tablet contains Isosorbide dinitrate 30 mg.

PHARMACOLOGICAL CLASSIFICATION:
7.1.4 Vasodilators - coronary and other medicines used in angina pectoris

PHAMACOLOGICAL ACTION:
Isosorbide dinitrate acts as a peripheral and coronary vasodilator which causes relaxation of smooth muscle; lowering of peripheral arterial blood pressure; decreased venous return and decreased left ventricular filling pressure.

INDICATIONS:
Angina Pectoris:
APO-ISOSORBIDE DINITRATE is used for the prevention and treatment of angina pectoris (pain of coronary artery disease). Oral APO-ISOSORBIDE DINITRATE is not intended to abort the acute anginal episode, but is widely regarded as useful in the prophylactic treatment of angina pectoris.
Congestive Cardiac Failure:
APO-ISOSORBIDE DINITRATE is also recommended in acute and chronic congestive cardiac failure including that that may be associated with myocardial infarction.
Therapy should be considered only as an adjunct to the more conventional modes of cardiac glycosides and diuretics.
Only in cases refractory to conventional therapy should APO-ISOSORBIDE DINITRATE be used alone or concomitantly with other vasodilators. APO-ISOSORBIDE DINITRATE is particularly effective in patients with increased left ventricular and diastolic pressure (LVEDP) and normal or approximately normal cardiac output, where pulmonary congestion (oedema) is the main problem.

CONTRA-INDICATIONS:
Hypersensitivity to any of the compounds. Patients with severe hypotension, hypovolaemia, marked anemia, constrictive pericarditis, heart failure due to obstruction, or raised intracranial pressure due to head trauma or cerebral haemorrhage. Isosorbide dinitrate may increase intra-ocular pressure in patients with closed-angle glaucoma and it is recommended that it should be avoided in such patients.
The efficacy and safety in children have not been established.

WARNINGS:
Data supporting the use of nitrates during the early days of the acute phase of myocardial infarction (the period during which clinical and laboratory findings are unstable) are insufficient to establish safety. Tolerance and cross-tolerance to other nitrates may develop with daily use but withdrawal restores the original sensitivity.
Alcohol may enhance the hypotensive effects when used concomitantly.

DOSAGE AND DIRECTIONS FOR USE:
Angina
APO-ISOSORBIDE DINITRATE 10 mg tablets: Administered orally. The dosage range is 5 mg (half tablet) to 30 mg four times a day with the average patient requiring 10 mg four times a day.
APO-ISOSORBIDE DINITRATE 30 mg tablets: Administered orally, and are indicated for patients requiring a higher dosage range to prevent or abort an anginal attack. The oral tablets may not be taken sublingually.
Congestive Cardiac Failure
In acute and chronic congestive cardiac failure both sublingual and oral forms of APO-ISOSORBIDE DINITRATE may be given at a dosage level determined by the supervising physician, usually not exceeding 5 - 10 mg every two hours sublingually, and 10 - 40 mg every six hours, orally.
The selection of sublingual or oral APO-ISOSORBIDE DINITRATE should be made on the basis of duration of action rather than the magnitude of response, since this is the major difference observed for these dosage forms. In order to obtain full therapeutic effect it is important that the dosage of sublingual and oral forms of APO-ISOSORBIDE DINITRATE be individualized in accordance with each patient's needs, clinical response and haemodynamic monitoring. APO-ISOSORBIDE DINITRATE therapy should begin with the lowest effective dose and further adjusted as necessary, based on the patient's pathophysiologic state. The initial dose depends on the assessment of the severity of the degree of heart failure.
For treatment of acute congestive cardiac failure, the sublingual form of APO-ISOSORBIDE DINITRATE is recommended.
For treatment of chronic congestive cardiac failure, the rapid acting sublingual form of APO-ISOSORBIDE DINITRATE should be administered initially to stabilize the patient's symptoms or to determine the magnitude of haemodynamic response, followed by the oral form for maintenance.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-Effects
Cutaneous vasodilation with flushing of the face and tachycardia.
Throbbing Headache is common and may be severe and persistent.
Transient episodes of dizziness and weakness as well as other signs of cerebral ischaemia associated with postural hypotension, may occasionally develop.
Large doses cause vomiting, restlessness, blurred vision, hypotension (which can be severe) syncope, and less frequently cyanosis, and methaemoglobinaemia; impairment of respiration and bradycardia may ensue.
An occasional individual exhibits a marked sensitivity to the hypotensive effects of nitrite and several responses (nausea, vomiting, weakness, restlessness, pallor, perspiration and collapse) can occur even with the usual therapeutic dose.
Alcohol may enhance this effect.
Medicine rash and/or exfoliative dermatitis may occasionally occur.
Precautions
APO-ISOSORBIDE DINITRATE should be used with caution in patients with severely impaired renal or hepatic Function, hypothyroidism, malnutrition, or hypothermia.
In the treatment of cardiac failure, whether acute or chronic, pulmonary capillary pressure should not be allowed to fall below 15 mm Hg or systolic blood pressure below physiological range in normal or hypertensive patients.
In patients with hypotension in the range of 90 - 100 mm Hg of systolic pressure there should be no fall at all. In sensitive patients APO-ISOSORBIDE DINITRATE may cause paradoxical side-effects which may increase ischaemia and may even lead to extension of myocardial damage and advanced congestive heart failure.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See Side-Effects and Special Precautions. Treatment is symptomatic and supportive.

IDENTIFICATION:
APO-ISOSORBIDE DINITRATE 10 mg (tablets): White to slightly off white, round tablets, one side flat-faced, beveled-edged, scored and engraved "APO" over "10", other side plain and convex.
APO-ISOSORBIDE DINITRATE 30 mg (tablets): White to slightly of white, round tablets, one side flat-faced, beveled-edged, scored and engraved "APO" over "I30", other side plain and convex.

PRESENTATION:
APO-ISOSORBIDE DINITRATE 10 mg (tablets):
White HDPE bottles containing 50, 100, 250, 500 and 1000 tablets.
Blister packs of 100 in strips of 10 tablets.
APO-ISOSORBIDE DINITRATE 30 mg (tablets):
White HDPE bottles containing 100, 500 and 1000 tablets.
Blister packs of 100 in strips of 10 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C, in a cool dry place in a well-closed container.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
APO-ISOSORBIDE DINITRATE 10 mg (Tablets): 32/7.1.4/0014.
APO-ISOSORBIDE DINITRATE 30 mg (Tablets): 32/7.1.4/0015

NAME AND BUSINESS ADDRESS OF APPLICANT:
Apotex S.A.
PHARMACEUTICAL INNOVATION
Apotex SA (Pty) Ltd
Corner Fleming and Watt Street
Meadowdale Ext. 1

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
22 May 1998

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2004