What are the guidelines for safe prescribing of Accutane (isotretinoin) in Canada?

Safe Accutane (Isotretinoin) Prescribing Guidelines in Canada

For safe isotretinoin prescribing in Canada, you must enroll in the iPLEDGE pregnancy prevention program, obtain monthly pregnancy tests for patients of childbearing potential, monitor liver function tests and lipid panels, and prescribe no more than 30-day supplies at 0.5-1 mg/kg/day with food for 15-20 weeks. 1

Mandatory Pregnancy Prevention Requirements

For Patients of Childbearing Potential

• Two forms of effective contraception must be used simultaneously starting 4 weeks before therapy, throughout treatment, and continuing for 3 years after discontinuation 2
• Pregnancy testing is required:
  • Within 2 weeks prior to starting therapy 2, 1
  • Monthly during treatment 2
  • Must be obtained within 7 days of specimen collection before each prescription 1
• Therapy should start on the second or third day of the next menstrual cycle 2, 1
• Patients must avoid alcohol completely, as it converts isotretinoin to etretinate, which has a significantly longer elimination half-life and extends the required contraception period 2

iPLEDGE Program Requirements

• All prescribers, pharmacies, and patients must be enrolled in the iPLEDGE REMS program 1
• Prescriptions require authorization from iPLEDGE before dispensing 1
• Only 30-day supplies can be dispensed at a time 1
• No automatic refills are permitted; each refill requires new prescription and authorization 1

Dosing Guidelines

Standard Dosing

• Recommended dose: 0.5-1 mg/kg/day divided into two doses taken with food for 15-20 weeks 2, 1
• Failure to take with food significantly decreases absorption 1
• Once-daily dosing has not been established as safe and is not recommended 1

Dose Adjustments

• Severe acne with scarring or primarily truncal involvement may require up to 2 mg/kg/day as tolerated 1
• Moderate acne: 0.3-0.5 mg/kg/day 2
• Daily dosing is preferred over intermittent dosing 2

Cumulative Dose Considerations

• Higher cumulative doses (>120 mg/kg) reduce relapse rates, particularly in young males with truncal acne 3
• If nodule count reduces by >70% before completing 15-20 weeks, therapy may be discontinued 1
• After 2 months off therapy, a second course may be initiated if severe nodular acne persists or recurs 1

Laboratory Monitoring

Required Baseline Tests

• Liver function tests (ALT, AST, GGT, alkaline phosphatase, bilirubin) 2
• Fasting lipid panel (cholesterol and triglycerides) 2
• Pregnancy test for patients of childbearing potential 2
• Fasting glucose in diabetic patients 2

Ongoing Monitoring

• Monitor only liver function tests and lipid panel; complete blood count monitoring is not needed in healthy patients 2, 4
• Repeat liver function tests and lipids at least once during treatment 2
• For the first 2 months: check every 2-4 weeks 2
• After initial 2 months: check every 3 months 2

Action Thresholds

• Discontinue if transaminases exceed 3 times upper normal limit 2
• Refer to gastroenterology if bilirubin >50 µmol/L or ALT >200 IU/L 2
• Refer to lipidologist if triglycerides >5 mmol/L 2
• Triglycerides approaching or exceeding 10 mmol/L warrant immediate discontinuation and urgent referral due to pancreatitis risk 2

Clinical Indications

Primary Indications

• Severe recalcitrant nodular acne (FDA-approved indication) 4, 1
• Any acne causing psychosocial burden or active scarring, regardless of objective severity 2, 4
• Acne unresponsive to standard oral and topical therapies 4
• Gram-negative folliculitis (after culture confirmation) 2, 4

Important Consideration

Do not delay isotretinoin in patients with scarring acne waiting for them to "fail" multiple therapies first—the presence of scarring itself qualifies them as candidates 4

Absolute Contraindications

• Pregnancy 2, 1
• Breastfeeding 2
• Hypersensitivity to isotretinoin or vitamin A 2
• Significant hepatic impairment (enzymes >2 times normal) 2
• Moderate to severe renal impairment 2

Drug Interactions to Avoid

• Tetracyclines: Risk of pseudotumor cerebri (benign intracranial hypertension) 2
• Vitamin A supplements: Do not exceed 2400-3000 IU daily 2
• Methotrexate: Increased hepatotoxicity risk 2
• Progestin-only contraceptives (mini-pill): Isotretinoin decreases efficacy 2
• Phenytoin: Altered protein binding 2

Common Side Effects and Management

Expected Mucocutaneous Effects

• Cheilitis occurs in nearly all patients (98%) 2, 5
• Dry skin, dry eyes, dry nose 2
• Photosensitivity—patients should avoid excessive UV exposure 2
• Advise against waxing for hair removal due to skin fragility 2

Metabolic Effects

• Elevated triglycerides and cholesterol are common 2
• Increased insulin sensitivity may cause hypoglycemia in diabetic patients 2
• Diabetic patients should check capillary glucose more frequently during early treatment 2

Neuropsychiatric Concerns

Population-based studies have not identified increased risk of neuropsychiatric conditions with isotretinoin, though patients should be educated about potential psychiatric symptoms 2, 4, 6

Inflammatory Bowel Disease

Population-based studies have not identified increased risk of inflammatory bowel disease with isotretinoin 2, 4

Special Precautions

Blood Donation

• Patients must not donate blood during therapy or for at least 1 year after discontinuation 2

Pediatric Use

• Safety and efficacy established in patients >12 years of age 2
• Not recommended in children <12 years due to risk of premature epiphyseal closure 2
• If used in children, monitor growth parameters carefully 2

Skeletal Monitoring

• Routine radiography has no role and is potentially harmful 2
• Targeted X-rays only if atypical musculoskeletal pain develops 2
• Long-term use effects on bone mineral density remain unknown 1

Surgery

• No need to discontinue isotretinoin for routine surgery—does not significantly affect wound healing 2

Dispensing Requirements

• Medication Guide must be provided with each dispensing 1
• Prescriptions must be filled within 30 days for patients who cannot become pregnant 1
• Prescriptions must be filled within 7 days of pregnancy test for patients who can become pregnant 1
• Isotretinoin must not be obtained through internet or means outside iPLEDGE 1

Common Pitfalls to Avoid

• Do not dismiss patients with "moderate" acne who have significant psychosocial impact—these patients should be considered as having severe acne for treatment purposes 2, 4
• Do not prescribe without confirming patient compliance with food instructions before increasing doses 1
• Do not assume neuropsychiatric or IBD risks preclude use—evidence does not support increased risk 2, 4
• Do not use tetracycline antibiotics concurrently due to pseudotumor cerebri risk 2