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Accutane (Isotretinoin) - Drug Interactions, Contraindications, Overdosage, etc



Drug Interactions

  • Vitamin A: Because ofthe relationship of Accutane to vitamin A, patients should be advisedagainst taking vitamin supplements containing vitamin A to avoid additivetoxic effects.
  • Tetracyclines: Concomitanttreatment with Accutane and tetracyclines should be avoided becauseAccutane use has been associated with a number of cases of pseudotumorcerebri (benign intracranial hypertension), some of which involvedconcomitant use of tetracyclines.
  • Micro-dosed Progesterone Preparations: Micro-dosed progesterone preparations ("minipills" that do not containan estrogen) may be an inadequate method of contraception during Accutanetherapy. Although other hormonal contraceptives are highly effective,there have been reports of pregnancy from female patients who haveused combined oral contraceptives, as well as transdermal patch/injectable/implantable/vaginalring hormonal birth control products. These reports are more frequentfor female patients who use only a single method of contraception.It is not known if hormonal contraceptives differ in their effectivenesswhen used with Accutane. Therefore, it is critically important forfemale patients of childbearing potential to select and commit touse 2 forms of effective contraception simultaneously, at least 1of which must be a primary form (see PRECAUTIONS).
  • Norethindrone/ethinyl estradiol: In a study of 31 premenopausal female patients with severe recalcitrantnodular acne receiving OrthoNovum® 7/7/7 Tablets as an oral contraceptiveagent, Accutane at the recommended dose of 1 mg/kg/day, did not induceclinically relevant changes in the pharmacokinetics of ethinyl estradioland norethindrone and in the serum levels of progesterone, follicle-stimulatinghormone (FSH) and luteinizing hormone (LH). Prescribers are advisedto consult the package insert of medication administered concomitantlywith hormonal contraceptives, since some medications may decreasethe effectiveness of these birth control products.
  • St. John's Wort: Accutane use is associated with depression in some patients (see WARNINGS: Psychiatric Disorders and ADVERSE REACTIONS: Psychiatric). Patients should be prospectively cautioned not to self-medicatewith the herbal supplement St. John's Wort because a possible interactionhas been suggested with hormonal contraceptives based on reports ofbreakthrough bleeding on oral contraceptives shortly after startingSt. John's Wort. Pregnancies have been reported by users of combinedhormonal contraceptives who also used some form of St. John's Wort.
  • Phenytoin: Accutane hasnot been shown to alter the pharmacokinetics of phenytoin in a studyin seven healthy volunteers. These results are consistent with thein vitro finding that neither isotretinoin nor its metabolites induceor inhibit the activity of the CYP 2C9 human hepatic P450 enzyme.Phenytoin is known to cause osteomalacia. No formal clinical studieshave been conducted to assess if there is an interactive effect onbone loss between phenytoin and Accutane. Therefore, caution shouldbe exercised when using these drugs together.
  • Systemic Corticosteroids: Systemic corticosteroids are known to cause osteoporosis. No formalclinical studies have been conducted to assess if there is an interactiveeffect on bone loss between systemic corticosteroids and Accutane.Therefore, caution should be exercised when using these drugs together.


The oral LD50 of isotretinoin is greaterthan 4000 mg/kg in rats and mice (>600 times the recommended clinicaldose of 1.0 mg/kg/day after normalization of the rat dose for totalbody surface area and >300 times the recommended clinical dose of1.0 mg/kg/day after normalization of the mouse dose for total bodysurface area) and is approximately 1960 mg/kg in rabbits (653 timesthe recommended clinical dose of 1.0 mg/kg/day after normalizationfor total body surface area). In humans, overdosage has been associatedwith vomiting, facial flushing, cheilosis, abdominal pain, headache,dizziness, and ataxia. These symptoms quickly resolve without apparentresidual effects.

Accutane causes serious birthdefects at any dosage (see Boxed CONTRAINDICATIONS AND WARNINGS). Female patients of childbearing potential who present with isotretinoinoverdose must be evaluated for pregnancy. Patients who are pregnantshould receive counseling about the risks to the fetus, as describedin the Boxed CONTRAINDICATIONSAND WARNINGS. Non-pregnant patients must be warnedto avoid pregnancy for at least one month and receive contraceptivecounseling as described in PRECAUTIONS. Educationalmaterials for such patients can be obtained by calling the manufacturer.Because an overdose would be expected to result in higher levels ofisotretinoin in semen than found during a normal treatment course,male patients should use a condom, or avoid reproductive sexual activitywith a female patient who is or might become pregnant, for 1 monthafter the overdose. All patients with isotretinoin overdose shouldnot donate blood for at least 1 month.



Allergic Reactions

Accutane is contraindicated in patients who are hypersensitiveto this medication or to any of its components. Accutane should notbe given to patients who are sensitive to parabens, which are usedas preservatives in the gelatin capsule (see PRECAUTIONS: Hypersensitivity).


  1. Peck GL, Olsen TG, Yoder FW, et al. Prolonged remissionsof cystic and conglobate acne with 13- cis -retinoic acid. N EnglJ Med 300:329-333, 1979.
  2. Pochi PE, Shalita AR, Strauss JS, Webster SB. Reportof the consensus conference on acne classification. J Am Acad Dermatol 24:495-500, 1991.
  3. Farrell LN, Strauss JS, Stranieri AM. The treatmentof severe cystic acne with 13- cis -retinoic acid: evaluation of sebum production and the clinical responsein a multiple-dose trial. J Am Acad Dermatol 3:602-611, 1980.
  4. Jones H, Blanc D, Cunliffe WJ. 13- cis -retinoic acid and acne. Lancet 2:1048-1049, 1980.
  5. Katz RA, Jorgensen H, Nigra TP. Elevation of serumtriglyceride levels from oral isotretinoin in disorders of keratinization. Arch Dermatol 116:1369-1372, 1980.
  6. Ellis CN, Madison KC, Pennes DR, Martel W, VoorheesJJ. Isotretinoin therapy is associated with early skeletal radiographicchanges. J Am Acad Dermatol 10:1024-1029, 1984.
  7. Dicken CH, Connolly SM. Eruptive xanthomas associatedwith isotretinoin (13- cis -retinoicacid). Arch Dermatol 116:951-952,1980.
  8. Strauss JS, Rapini RP, Shalita AR, et al. Isotretinointherapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 10:490-496, 1984.

OrthoNovum 7/7/7 is a registered trademark of Ortho-McNeilPharmaceutical, Inc.

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