Accutane® (Isotretinoin) Side Effects, Safety and Risks

Common Side-Effects

• Dry Lips and Skin
• Dry Eyes and Vision
• Nasal Dryness
• Thinning Hair:
• Photosensitivity:
• Fatigue (15-20%)
• Headaches (5-16%)

Organs That May Be Affected

• Neurologic
• Hepatic
• Bones
• Lipids
• Muscloskeletal
• Leukopenia

Dry Itchy Eyes

• Common problem (blepharoconjunctivitis)
• Loss of visual acuity uncommon.
• Rare night blindness which may be permanent

Management Options

• Stop wearing lenses
• Frequent use of artificial tears
• If possible loss of visual acuity or night vision changes
• Opthalmological opinion should be sought

Dry Skin and Lips

• Dry lips:
  • Almost all patients have very dry lips. The lack of dryness raises the possibility of the patient either not taking the medication or not ingesting the drug with food.
  • Secondary bacterial infection is common

• Dry Skin:
  • The face and backs of the hands and forearms are usually the driest. 87% of patients
  • There is often a low grade dermatitis present.
  • Look out for secondary staph infection.

Management Options

• Dry Lips:
  • Frequent use of vaseline and lip balm containing sunscreen.
  • Antibiotic ointments if inflammation or crusting

• Dry Skin:
  • Avoid drying cleansers
  • Regular moisturizing

Uncommon Eye Side Effects

• Corneal opacities which do not impair vision and have been show o disappear after discontinuation of drug
• Cataracts have been reported in adults
• Retinal changes leading to night blindness. Rarely these changes can be permanent

Other Side-effects

• Tetracyclines – may increase risk of pseudotumour cerebri – avoid concomitant use
• Pancreatitis – rare
• in patients with normal or elevated triglycerides
• d/c drug
• also d/c if triglycerides cannot be controlled due to increase risk of pancreatitis
• Hepatoxicity – increased lfts, usually resolve if continue with therapy
• Inflammatory bowel disease -d/c drug
• may or may not result in resolution of sx
• Rhabdomyolysis – rare
• CVS: palipitations, tachycardia, stroke
• Endocrine: altered blood sugars
• Heme: anemia, thrombocytopenia rare
• Cuts that take longer to heal
• Facial redness, flushing – more common .in fair haired people

Pregnancy

• This drug is teratogenic and causes fetal abnormalities.

Bones

• Hyperostosis, osteophytes (bony spurs) may develop, but are usually of little consequence.
• There is a possible risk of osteoporosis, osteopena, bone #, increased risks with high does, long-term, multiple courses.

Neurological

• A pseudotumor in the cerebrum can occur, which can cause increased brain fluid pressure, headaches, vomiting, and visual disturbances.
• Depression and suicidal thoughts have been reported in some patients.

Lipids

• Cholesterol/ triglyceride levels may increase, a short-term increase in cholesterol, though this is not thought to be very significant. The increase is dose related.
• Usually reversible with D/C therapy. Full impact on lipids seen in about 4 weeks following therapy
• Incidence of hypertriglyceridemia is 1 in 4
• Pancreatitis is a risk if your triglycerides rise quickly.
• This may be a marker for familial hyperlipidaemia. And may be an indication to check lipid levels in 1st degree relatives

CNS Risks

Product Monograph

• A pseudotumor in the cerebrum can occur, which can cause increased brain fluid pressure, headaches, and vomiting.
• Tinnitus, hearing impairment has been reported
• Visual disturbances, corneal opacities usually resolve on stopping the drug
• Decreased night vision may or may not resolve with cessation of therapy
• Dizzy spells, drowsy, seizure, lethargy, malaise, nervousness may occur

Clinical Experience

• Headaches persist with benign intracranial hypertension and are present on waking. May lift as the day progresses, nausea, vomiting and visual changes are warning signs.
• Opthalmologic exam is required. Refer to Neurologist if in doubt.

Depression caused by Isotretinoin?

• Anxiety and depression and decrease quality of life is associated with acne.
• Depression and suicide is relatively common in the teenage population.
• Accutane packet insert warns of possible psychiatric side effects including aggressive and violent behaviour.
• Mood swings, depressive symptoms and suicidal thoughts may be a very uncommon idoisyncratic reaction for those on Isotretinoin.
• A causal relationship has not been firmly established.
• Awareness of mood changes in all teenagers with acne is important.
• Close monitoring of mood in all patients on Isotretinoin is prudent.
• Clinical experience shows that depressive symptoms, if they occur, disappear quickly in the vast majority on discontinuation of the drug.

Publications About Psyche and Isotretinoin

• Arch Dermatol 2000 oct;136(10):1231-6 – “No evidence.”
• Clin Exp Dermatol 1991 may;16(30:210-1 – Psych benefit of Isotretinoin use.
• J Am Acad Dermatol 2001 nov;45(5):s168-75 – be aware of risk factors for suicide and monitor for depressive symptoms.
• J Am Acad Dermatol 1987 jul;17(10:25-32 – Reduced anxiety and depression from Isotretinoin use.
• Australasian J Dermatol.2002 nov;43(4):262-8 – No link with Isotretinoin and depression apart from being a rare, unpredictable idiosyncratic side-effect.
• Austral N Z J Psychiatry 2003 feb;37(1):78-84 – Causal relationship for depression not clearly established. A positive psychological effect in the majority.Depression may occur as an idiosyncratic side-effect and requires detection and treatment.

Monitoring

• CBC, Cholesterol, Trigycerides
• ALT, AST

• LFTS During Use:
  • Repeat in 4 weeks. If ALT is 2-3 times baseline repeat testing in 3 weeks and reduce the dose.
  • If the levels climb higher d/c the drug and retest in 3 weeks

• Pregnancy Testing:
  • Two negative urine tests prior to initiating therapy.
  • Repeat monthly prior to renewal of prescription.

• Lipids:
  • Fasting Lipids at baseline then every 1-2 weeks until response is established.
  • Monitoring of Lipids next slide
  • Triglyceride elevation during Isotretinoin use may be a marker of familial combined hyperlipidemia
  • See Ann Inter Med 2002:136:582-589
  • Trigycerides and cholesterol elevation of the triglycerides above 7 may be associated with pancreatitis.
  • Cholesterol elevation during therapy may not pose a short term threat.
  • Familial combined hyperlipidemia is associated with a risk of hyperlipidemia, diabetes, hypertension and obesity in later life
  • Check lipids of first degree relatives of Isotretinoin patients who have elevated triglycerides