Isotretinoin

DEA Class; Rx

Common Brand Names; Amnesteem, Claravis, Myorisan, Absorica, Zenatane, Absorica LD

• Acne Agents, Systemic; 
• Retinoid-like Agents

Oral retinoid; synthetic 13-cis isomer of naturally occurring tretinoin
Used primarily for severe, recalcitrant nodular acne
Due to teratogenicity potential, only available through isotretinoin iPLEDGE REMs program

Indicated for the treatment of severe recalcitrant cystic acne vulgaris (nodular acne) in patients with multiple inflammatory nodules with a diameter of at least 5 mm.

Pregnancy 

Hypersensitivity to isotretinoin or vitamin A

• Cheilitis (90%)
• Xerosis
• Xerostomia
• Dry nose
• Epistaxis
• Pruritus
• Conjunctivitis (including blepharoconjunctivitis) (40%)
• Irritation (40%)
• Increased erythrocyte sedimentation rates (40%)
• Thinning of hair (which has persisted in rare instances)
• Palmoplantar desquamation
• Skin fragility
• Skin infections (eg, paronychial infections)
• Rash (including erythema, seborrhea, eczema), photosensitivity
• Hypertriglyceridemia (25%)
• Bone or joint pain
• Generalized muscle aches
• Arthralgia
• Decreased HDLs (15%)
• Increased LFTs (15%)
• Increased CPK (12-24%)
• Decreased hemoglobin concentration and hematocrit
• Decreased erythrocyte and leukocyte counts
• Increased platelet count

Significant adverse effects are associated with isotretinoin use

Neutropenia and agranulocytosis (rare) reported; discontinue if white cell counts decrease significantly

Embryofetal toxicity; major congenital malformations, spontaneous abortions, and premature births documented (see Black Box Warnings)

Do not donate blood during therapy and for 1 month after discontinuing treatment, because of embryofetal toxicity risk

Restricted distribution program (iPLEDGE), a risk management program to minimize pregnancy exposure, has been implemented (see Black Box Warnings)

Microdosed, progesterone-only preparations (‘minipills’) are an inadequate method of contraception during treatment

Pseudotumor cerebri reported; some reports involved concomitant tetracycline use; concomitant treatment with tetracyclines should be avoided; early signs and symptoms of intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances; screen patients with these symptoms for papilledema and, if present, discontinue therapy immediately and refer patient to a neurologist for further diagnosis and care

Serious skin reactions reported (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis); discontinue therapy if skin reaction occurs

Acute pancreatitis reported with either elevated or normal serum triglyceride levels, including rare instances of fatal hemorrhagic pancreatitis; discontinue if unable to control hypertriglyceridemia; discontinue therapy if pancreatitis occurs

Increased triglycerides and total cholesterol levels reported; whereas, decreased HDL-cholesterol reported

Hearing impairment reported and may persist after discontinuing therapy; patients who experience tinnitus or hearing impairment should discontinue treatment and be referred for specialized care for further evaluation

Hepatitis may occur; mild to moderate liver enzymes elevations also reported; some normalized with dosage reduction or continued administration of drug’ if normalization does not readily occur or if hepatitis is suspected during treatment, therapy should be discontinued

Associated with inflammatory bowel disease (including regional ileitis); discontinue immediately if abdominal pain, rectal bleeding, or severe diarrhea occurs

Negative effect on bone mineral density reported; caution with childhood osteoporosis, osteomalacia, chronic corticosteroid use, or anorexia nervosa

Musculoskeletal symptoms, including arthralgia and rhabdomyolysis may occur; consider discontinuing therapy if any significant abnormality found

Skeletal hyperostosis observed in clinical trial for keratinization disorders

Avoid prolonged exposure to uv rays or sunlight

Premature epiphyseal closure reported spontaneously with normal doses

Therapy is contraindicated during pregnancy; it can cause fetal harm when administered to a pregnant patient

There are no data on either animal or human milk, effects on breastfed infant, or on milk production

2 mg/kg/day PO (all formulations EXCEPT Absorica LD) for cystic acne; 1.6 mg/kg/day PO (Absorica LD) for cystic acne.

2 mg/kg/day PO (all formulations EXCEPT Absorica LD) for cystic acne; 1.6 mg/kg/day PO (Absorica LD) for cystic acne.

1 mg/kg/day PO (all formulations EXCEPT Absorica LD) for cystic acne; 0.8 mg/kg/day PO (Absorica LD) for cystic acne.

12 years: 1 mg/kg/day PO (all formulations EXCEPT Absorica LD) for cystic acne; 0.8 mg/kg/day PO (Absorica LD) for cystic acne.
younger than 12 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Isotretinoin 

capsule

• 10mg (Absorica, Amnesteem, Claravis, Myorisan, Zenatane)
• 20mg (Absorica, Amnesteem, Claravis, Myorisan, Zenatane)
• 25mg (Absorica)
• 30mg (Absorica, Claravis, Zenatane)
• 35mg (Absorica)
• 40mg (Absorica, Amnesteem, Claravis, Myorisan, Zenatane)

capsule, micronized (Absorica LD)

• 8mg
• 16mg
• 20mg
• 24mg
• 28mg
• 32mg