|ISOTRETINOIN (13-cis-RETINOIC ACID)
Classifications: antiacne (retinoid); Therapeutic: antiacne; antineoplastic
Pregnancy Category: X
10 mg, 20 mg, 40 mg capsules
Highly toxic metabolite of retinol (vitamin A). Principal actions: regulation of cell (e.g., epithelial) differentiation
and proliferation and of altered lipid composition on skin surface. Decreases sebum secretion by reducing sebaceous gland
size; inhibits gland cell differentiation; blocks follicular keratinization.
Has antiacne properties and may be used as a chemotherapeutic agent for epithelial carcinomas.
Treatment of severe recalcitrant cystic or conglobate acne in patient unresponsive to conventional treatment, including
Lamellar ichthyosis, oral leukoplakia, hyperkeratosis, acne rosacea, scarring gram-negative folliculitis; adjuvant therapy
of basal cell carcinoma of lung and cutaneous T-cell lymphoma (mycosis fungoides); psoriasis; chemoprevention for prostate
Tinnitus; hypersensitivity to parabens (preservatives in the formulation), retinoid hypersensitivity, leukopenia, neutropenia;
UV exposure; pregnancy (category X), females of childbearing age, lactation.
Coronary artery disease; major depression, psychosis, history of suicides, alcoholism; hepatitis, hepatic disease; visual
disturbance; rheumatologic disorders, osteoporosis; history of pancreatitis, inflammatory bowel disease; diabetes mellitus;
obesity; retinal disease; elevated triglycerides, hyperlipidemia.
Route & Dosage
Adult: PO 0.51 mg/kg/d in 2 divided doses (max: recommended dose 2 mg/kg/d)
Disorders of Keratinization
Adult: PO Up to 4 mg/kg/d in divided doses
- Give with or shortly after meals.
- Reassess regimen after 2 wk of treatment and dose adjusted as warranted.
- Note: A single course of therapy provides adequate control in many patients. If a second course is necessary, it is delayed at
least 8 wk because improvement may continue without the drug.
- Store in tight, light-resistant container. Capsules remain stable for 2 y.
Adverse Effects (≥1%)Body as a Whole:
Most are dose-related (i.e., occurring at doses >1 mg/kg/d), reversible with termination of therapy. CNS:
Lethargy, headache, fatigue
, visual disturbances, pseudotumor cerebri, paresthesias, dizziness, depression
, psychosis, suicide
(rare). Special Senses:
Reduced night vision, dry eyes, papilledema, eye irritation, conjunctivitis,
corneal opacities. GI: Dry mouth,
anorexia, nausea, vomiting, abdominal pain, nonspecific GI symptoms
, acute hepatotoxic reactions
(rare), inflammation and bleeding of gums, increased AST, ALT, acute pancreatitis
Decreased Hct, Hgb, elevated sedimentation rate. Musculoskeletal: Arthralgia
; bone, joint, and muscle pain and stiffness; chest pain, skeletal hyperostosis (especially in athletic people
and with prolonged therapy), mild bruising. Skin: Cheilitis,
skin fragility, dry skin, pruritus, peeling of face, palms, and soles; photosensitivity (photoallergic and phototoxic),
, skin infections, petechiae, rash, urticaria, exaggerated healing response (painful exuberant granulation tissue
with crusting), brittle nails, thinning hair. Respiratory:
Epistaxis, dry nose. Metabolic:
Hyperuricemia, increased serum concentrations of triglycerides by 5070%, serum
cholesterol by 1520%, VLDL cholesterol by 5060%, LDL cholesterol by 1520%.
InteractionsDrug: vitamin a supplements
; decreases effectiveness of estrogen
in oral form as well as topical/injectable/implantable/insertable estrogen
hormonal birth control
Rapid absorption after slow dissolution in GI tract; 25% of administered drug reaches systemic circulation. Peak:
3.2 h. Distribution:
Not fully understood; appears in liver, ureters, adrenals, ovaries and lacrimal glands. Metabolism:
In liver; enterohepatically cycled. Elimination:
In urine and feces in equal amounts. Half-Life:
Assessment & Drug Effects
- Lab tests: Determine baseline blood lipids at outset of treatment, then at 2 wk, 1 mo, and every month thereafter throughout
course of therapy; liver function tests at 2- or 3-wk intervals for 6 mo and once a month thereafter during treatment.
- Report signs of liver dysfunction (jaundice, pruritus, dark urine) promptly.
- Monitor closely for loss of glycemic control in diabetic and diabetic-prone patients.
- Monitor for development of depression and suicidal ideation.
- Note: Persistence of hypertriglyceridemia (levels above 500800 mg/dL) despite a reduced dose indicates necessity to stop
drug to prevent onset of acute pancreatitis.
Patient & Family Education
- Maintain drug regimen even if during the first few weeks transient exacerbations of acne occur. Recurring symptoms may signify
response of deep unseen lesions.
- Discontinue medication at once and notify physician if visual disturbances occur along with nausea, vomiting, and headache.
- Rule out pregnancy within 2 wk of starting treatment. Use a reliable contraceptive 1 mo before, throughout, and 1 mo after
therapy is discontinued.
- Do not self-medicate with multivitamins, which usually contain vitamin A. Toxicity of isotretinoin is enhanced by vitamin
- Avoid or minimize exposure of the treated skin to sun or sunlamps. Photosensitivity (photoallergic and phototoxic) potential
is high; risk of skin cancer may be increased by this drug.
- Notify physician immediately of abdominal pain, rectal bleeding, or severe diarrhea, which are possible symptoms of drug-induced
inflammatory bowel disease.
- Keep lips moist and softened (use thin layer of lubricant such as petroleum jelly); dry mouth and cheilitis (inflamed, chapped
lips), frequent adverse effects of isotretinoin.
- Notify physician of joint pain, such as pain in the great toe (symptom of gout and hyperuricemia).