ADALAT XL

1 Dosing Considerations Dosage should be individualized depending on patient tolerance and response. 2 Recommended Dose and Dosage Adjustment In general, titration steps should proceed over a 7-14 day period so that the physician can assess the response to each dose level before proceeding to higher doses.

Since steady -state plasma levels are achieved on the second day of dosing, if symptoms so warrant, titration may proceed more rapidly provided that the patient is closely monitored. Chronic Stable Angina Therapy with ADALAT XL should normally be initiated with 30 mg once daily.

Experience with doses greater than 90 mg daily in patients with angina is limited, therefore, doses greater than 90 mg daily are not recommended. Angina patients controlled on ADALAT capsules alone or in combination with beta blockers may be safely switched to ADALAT XL tablets at the nearest equivalent daily dose.

Subsequent titration to higher or lower doses may be necessary and should be initiated as clinically warranted. Hypertension Therapy should normally be initiated with 20 mg* or 30 mg once daily. The usual maintenance dose is 30 mg to 60 mg* once daily.

Doses greater than 90 mg daily are not recommended. * Note: ADALAT XL 20 mg and 60 mg are not available in Canada. ADALAT XL Product Monograph Page 5 of 40 No "rebound effect" has been observed upon discontinuation of ADALAT XL. However, if discontinuation of nifedipine is necessary, sound clinical practice suggests that the dosage should be decreased gradually under close physician supervision.

Pediatrics (< 18 years of age) Health Canada has not authorized an indication for pediatric use. Patients with Hepatic Impairment In patients with mild impaired liver function, careful monitoring should be performed and a dose reduction may be necessary.

3 Pharmacokinetics - Special Populations and Conditions, Hepatic Insufficiency). Patients with Diabetes ADALAT XL may produce hyperglycemia and lead to loss of glucose control. 1 Special Populations). 4 Drug-Drug Interactions). 4 Administration For oral use.

ADALAT XL (nifedipine extended-release tablets) must be swallowed whole and should not be chewed or divided. 5 Missed Dose If a dose of ADALAT XL is missed, the dose should be taken as soon as the patient remembers prior to the next scheduled dose.

). These responses have usually occurred during initial titration or at the time of subsequent upward dosage adjustment and may be more likely in patients on concomitant beta blockers. If excessive hypotension occurs, dosage should be lowered or the drug should be discontinued (see 2 CONTRAINDICATIONS).

Severe hypotension and/or increased fluid volume requirements have been reported in patients receiving nifedipine, with a beta blocker, who underwent coronary artery bypass surgery using high-dose fentanyl anesthesia. The interaction with high-dose fentanyl appears to be due to the combination of nifedipine and a beta blocker, but the possibility that it may occur with nifedipine alone, with low doses of fentanyl in other surgical procedures, or with other narcotic analgesics cannot be ruled out.

In nifedipine-treated patients where surgery using high-dose fentanyl anesthesia is contemplated, the physician should be aware of these potential problems, and if the patient's condition permits, sufficient time (at least 36 hours) should be allowed for nifedipine to be washed out of the body prior to surgery.

The following information should be taken into account in those patients who are being treated for hypertension as well as angina. Increased Angina and/or Myocardial Infarction Rarely, patients, particularly those who have severe obstructive coronary artery disease have developed well-documented increased frequency, duration and/or severity of angina or acute myocardial infarction on starting nifedipine or at the time of dosage increase.

The mechanism of the response is not established. ADALAT XL Product Monograph Page 8 of 40 Since there has not been a study of ADALAT XL in acute myocardial infarction reported, similar effects of ADALAT XL to that of immediate-release nifedipine cannot be excluded.

Immediate- release nifedipine is contraindicated in acute myocardial infarction. Beta-blocker Withdrawal Patients with angina recently withdrawn from beta blockers may develop a withdrawal syndrome with increased angina, probably related to increased sensitivity to catecholamines.

). Hypertension ADALAT XL is indicated in the management of mild to moderate essential hypertension. Combination of ADALAT XL with a diuretic has been found compatible and has shown added antihypertensive effect. Concurrent administration of low doses of ADALAT XL and enalapril has been shown to produce an enhanced antihypertensive effect with no additional safety concerns when compared to that observed with either of the monotherapies.

Safety of concurrent use of ADALAT XL with other antihypertensive agents has not been established. 1 Pediatrics Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

4 Geriatrics). 2 CONTRAINDICATIONS ADALAT XL (nifedipine extended-release tablets) is contraindicated in: • Pregnancy, and in women of childbearing potential. Fetal malformations and adverse effects on pregnancy have been reported in animals.

(see 16 NON-CLINICAL TOXICOLOGY - Reproductive and Developmental Toxicology). ADALAT XL Product Monograph Page 4 of 40 • Breastfeeding • Patients who are hypersensitive to nifedipine, or to any ingredient in the formulation or component of the container.

For a complete listing, see 6 DOSAGE FORMS, COMPOSITION AND PACKAGING • Patients with a known hypersensitivity to other dihydropyridines calcium antagonists, because of the theoretical risk of cross-reactivity • Patients with severe hypotension or cardiovascular shock.

• Combination with rifampicin because effective plasma levels of nifedipine may not be achieved due to induction of the enzyme metabolizing nifedipine. • Patients with a Kock pouch (ileostomy after proctocolectomy). 1 Dosing Considerations Dosage should be individualized depending on patient tolerance and response.

2 Recommended Dose and Dosage Adjustment In general, titration steps should proceed over a 7-14 day period so that the physician can assess the response to each dose level before proceeding to higher doses. Since steady -state plasma levels are achieved on the second day of dosing, if symptoms so warrant, titration may proceed more rapidly provided that the patient is closely monitored.

ADALAT XL (nifedipine extended-release tablets) is contraindicated in: • Pregnancy, and in women of childbearing potential. Fetal malformations and adverse effects on pregnancy have been reported in animals. (see 16 NON-CLINICAL TOXICOLOGY - Reproductive and Developmental Toxicology).

ADALAT XL Product Monograph Page 4 of 40 • Breastfeeding • Patients who are hypersensitive to nifedipine, or to any ingredient in the formulation or component of the container. For a complete listing, see 6 DOSAGE FORMS, COMPOSITION AND PACKAGING • Patients with a known hypersensitivity to other dihydropyridines calcium antagonists, because of the theoretical risk of cross-reactivity • Patients with severe hypotension or cardiovascular shock.

• Combination with rifampicin because effective plasma levels of nifedipine may not be achieved due to induction of the enzyme metabolizing nifedipine. • Patients with a Kock pouch (ileostomy after proctocolectomy). • Patients with moderate or severe hepatic impairment (see 7 WARNINGS AND PRECAUTIONS) • Patients with severe gastrointestinal (GI) obstructive disorders (see 7 WARNINGS AND PRECAUTIONS)