isotretinoin

eye-soe-TRET-i-noyn

Therapeutic Classification: antiacne agents

Pharmacologic Classification: retinoids

REMS

Severe recalcitrant nodular acne in patients with multiple inflammatory nodules having a diameter of ≥5 mm and that are unresponsive to more conventional therapy, including systemic antibiotics.

A metabolite of vitamin A (retinol) reduces sebaceous gland size and differentiation.

Therapeutic effects:

Diminution and resolution of severe acne. May also prevent abnormal keratinization.

Absorption: Rapidly absorbed following (23–25%) oral administration (bioavailability of Absorica LD higher than that of Absorica); absorption ↑ when taken with a high-fat meal.

Distribution: Widely distributed to tissues.

Protein Binding: 99.9%.

Metabolism/Excretion: Metabolized by the liver and excreted in the urine and feces.

Half-Life: 10–20 hr.

(diminution of acne)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	up to 8 wk	unknown

Contraindicated in:

Hypersensitivity to retinoids, glycerin, soybean oil, or parabens;
Patients planning to donate blood;
OB:
Pregnancy
;
Lactation: Lactation.

Use Cautiously in:

Pre-existing hypertriglyceridemia;
Diabetes mellitus;
History of alcohol abuse, psychosis, depression, or suicide attempt;
Obese patients;
Inflammatory bowel disease;
Rep:
Women of reproductive potential
;
Pedi: Children <12 yr (safety and effectiveness not established).

CV: edema

Derm: pruritus, palmar desquamation, photosensitivity, skin infections, STEVENS-JOHNSON SYNDROME (SJS), thinning of hair, TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: conjunctivitis, epistaxis, ↓night vision, blurred vision, contact lens intolerance, corneal opacities, dry eyes

Endo: hyperglycemia

F and E: ↑thirst

GI: cheilitis, dry mouth, nausea, vomiting, abdominal pain, anorexia, hepatitis, pancreatitis

Hemat: anemia

Metab: ↓HDL-C, hypercholesterolemia, hypertriglyceridemia, ↑appetite, hyperuricemia

MS: arthralgia, back pain, muscle/bone pain (↑ in adolescents), hyperostosis

Neuro: behavior changes, depression, PSEUDOTUMOR CEREBRI, psychosis, SUICIDAL THOUGHTS/BEHAVIORS

Drug-drug:

Additive toxicity with vitamin A and drugs having anticholinergic properties.
↑risk of pseudotumor cerebri with tetracycline or minocycline.
Alcohol↑ risk of hypertriglyceridemia.
Drying effects ↑ by concurrent use of benzoyl peroxide, sulfur, tretinoin, and other topical agents.

Drug-Food:

Excessive ingestion of foods high in vitamin A may result in additive toxicity.

Absorica and Absorica LD are not interchangeable.
PO (Adults and Children ≥12 yr): 0.5–1 mg/kg/day (may use up to 2 mg/kg/day for very severe disease) in 2 divided doses for 15–20 wk. Once discontinued, if relapse occurs, therapy may be reinstituted after an 8-wk rest period. Absorica LD: 0.4–0.8 mg/kg/day (may use up to 1.6 mg/kg/day for very severe disease) in 2 divided doses for 15–20 wk. Once discontinued, if relapse occurs, therapy may be reinstituted after an 8-wk rest period.

(Generic available)

Capsules: 10 mg; 20 mg; 25 mg; 30 mg; 35 mg; 40 mg
Capsules (Absorica LD): 8 mg; 16 mg; 24 mg; 32 mg

Assess skin prior to and periodically during therapy. Transient worsening of acne may occur at initiation. Note number and severity of cysts, degree of skin dryness, erythema, and itching.
Assess for allergy to parabens; capsules contain parabens as a preservative.
Monitor for behavioral changes (depression, psychosis, aggression, suicidal ideation). If behavioral changes occur, immediately discontinue isotretinoin and treat as indicated.
Monitor for signs and symptoms of intracranial hypertension. If signs of pseudotumor cerebri with papilledema occur, immediately discontinue isotretinoin and refer to neurologist.
Assess for rash periodically during therapy. May cause SJS or TEN. If severe rash or rash associated with generalized symptoms occurs, discontinue isotretinoin.

Lab Test Considerations:

Verify two negative sequential serum or urine pregnancy tests with a sensitivity ≥25 mIU/mL before receiving initial Rx and monthly before each new Rx.
- Monitor liver enzymes (AST, ALT, LDH) before starting therapy, after 1 mo of therapy, and periodically thereafter. If hepatitis suspected, discontinue isotretinoin.
- Monitor fasting serum cholesterol, HDL-C, and triglycerides before initiating therapy, at 1–2 wk intervals until lipid response is established, and periodically thereafter.
- Obtain baseline and periodic CBC, urinalysis, and metabolic panel. May ↑ blood glucose, CK, platelets, sedimentation rate, and uric acid. May ↓ RBC and WBC. May cause proteinuria, RBCs and WBCs in urine.

Do not confuse isotretinoin with tretinoin.
REMS: Health care providers who prescribe and pharmacies who dispense isotretinoin must enroll in iPLEDGE REMS (www.ipledgeprogram.com, 1-866-495-0654), and patients must meet all requirements.
PO: Administer without regard to food. Administer with a full glass of liquid to ↓ risk of esophageal irritation. DNC: Do not crush or open capsules.

REMS: Explain purpose and side effects of medication as well as iPLEDGE REMS and its requirements. The patient must readPatient Information and sign consent form prior to initiation of therapy.
Advise patient to omit dose if missed and then resume as scheduled; do not double doses.
Explain to patient that a temporary worsening of acne may occur at beginning of therapy.
Advise patient and family to notify health care provider if rash, visual or hearing changes, headache, nausea or vomiting, or mood changes (suicidal ideation or attempt, depression, anxiety, agitation, restlessness, insomnia) occur.
May cause sudden ↓ in night vision. Caution patient to avoid driving at night until response is known.
Advise patient to consult with health care provider before using other acne preparations while taking isotretinoin.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John's wort.
Instruct patient not to take vitamin A supplements and to avoid excessive ingestion of foods high in vitamin A (liver, fish liver oils, egg yolks, yellow-orange fruits and vegetables, dark green leafy vegetables, whole milk, vitamin A–fortified skim milk, butter, margarine) to avoid vitamin A toxicity.
Advise patient to avoid alcoholic beverages during therapy, as this may further ↑ triglycerides.
Inform patient that dry skin and chapped lips will occur. Lubricant to lips may help cheilitis.
Instruct patient that oral rinses, good oral hygiene, and sugarless gum or candy may help minimize dry mouth and to notify health care provider if dry mouth persists >2 wk.
Discuss possibility of excessively dry eyes with patients who wear contact lenses. Patient should contact health care provider about eye lubricant and may need to switch to glasses during and for up to 2 wk following therapy.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions. Consult health care provider about sunscreen, as some sunscreens may worsen acne.
Inform patients with diabetes that difficulty controlling blood glucose may occur.
Instruct patient to report burning of eyes, abdominal pain, and diarrhea, to health care provider.
Advise patient not to donate blood during and for ≥1 mo after therapy to prevent a pregnant patient from receiving the blood.
Rep:
May cause fetal harm. Instruct women of reproductive potential to use 2 forms of contraception 1 mo before, during, and for ≥1 mo after discontinuation of therapy. Advise that patient must have 2 negative pregnancy tests before initiating therapy. 1st test is when decision is made to prescribe isotretinoin; 2nd test is after 2 forms of contraception are used for 1 mo and during 1st 5 days of menstrual period immediately preceding beginning of therapy. For patients with amenorrhea, 2nd test should be done 11 days after last act of unprotected sexual intercourse. Pregnancy test must be repeated every month prior to receiving prescription. Patient should discontinue medication and inform health care provider immediately if pregnancy is suspected during or 1 mo after therapy. If pregnancy occurs, report immediately to the FDA via MedWatch (1-800-FDA-1088) and also to the iPLEDGE pregnancy registry (1-866-495-0654 or www.ipledgeprogram.com). Recommended consent form prepared by manufacturer stresses fetal risk. Parents of minors should also read and sign form. Yellow self-adhesive qualification stickers completed by prescriber must accompany prescription. Advise patient to avoid breastfeeding during and for ≥8 days after last dose.
Inform patient of need for medical follow-up. Periodic lab tests may be required.

Decrease in the number and severity of cysts in severe acne. Therapy may take 4–5 mo before full effects are seen. Therapy is discontinued when the number of cysts is ↓ by 70% or after 5 mo. Improvement may occur after discontinuation of therapy; therefore, a delay of ≥8 wk is recommended before a second course of therapy is considered.

Absorica, Absorica LD, Accutane, Amnesteem, Claravis, ~~Myorisan,~~ Zenatane

Clarus, Epuris

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