Brands, Medical Use, Clinical Data
Drug Category
- Anti-acne Agents
- Skin and Mucous Membrane Agents
Dosage Forms
Brands / Synonyms
Accutane; Accutane Roche; Amnesteem; Avita; Claravis; Renova; Retin-A; Retin-A Micro; Retinoic acid; Retinoic acid, all trans isomer; Sotret; Tretinoin; Vesanoid; Vitamin A acid
Indications
For the treatment of severe recalcitrant nodular acne
Pharmacology
Isotretinoin, a retinoid, is indicated in the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. "Severe," by definition, means "many" as opposed to "few or several" nodules. Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion. The decrease in sebum secretion is temporary and is related to the dose and duration of treatment with Accutane, and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation.
Mechanism of Action
Isotretinoin noticeably reduces the production of sebum and shrinks the sebaceous glands. It stabilises keratinization and prevents comedones from forming. The exact mechanism of action is unknown, however it is known that it alters DNA transcription.
Absorption
Not Available
Toxicity
Not Available
Biotrnasformation / Drug Metabolism
Not Available
Contraindications
Pregnancy: Category X. Allergic Reactions Accutane is contraindicated in patients who are hypersensitive to this medication or to any of its components. Accutane should not be given to patients who are sensitive to parabens, which are used as preservatives in the gelatin capsule.
Drug Interactions
· Vitamin A: Because of the relationship of Accutane to vitamin
A, patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic
effects.
· Tetracyclines: Concomitant treatment with Accutane and
tetracyclines should be avoided because Accutane use has been associated with a number of cases of pseudotumor
cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines.
· Micro-dosed Progesterone Preparations: Micro-dosed
progesterone preparations ("minipills" that do not contain an estrogen) may be an inadequate method of contraception
during Accutane therapy. Although other hormonal contraceptives are highly effective, there have been reports of
pregnancy from women who have used combined oral contraceptives, as well as topical/injectable/implantable/insertable
hormonal birth control products. These reports are more frequent for women who use only a single method of
contraception. It is not known if hormonal contraceptives differ in their effectiveness when used with Accutane.
Therefore, it is critically important for women of childbearing potential to select and commit to use 2 forms of
effective contraception simultaneously, at least 1 of which must be a primary form, unless absolute abstinence is the
chosen method, or the patient has undergone a hysterectomy.
· Phenytoin: Accutane has not been shown to alter the
pharmacokinetics of phenytoin in a study in seven healthy volunteers. These results are consistent with the in vitro
finding that neither isotretinoin nor its metabolites induce or inhibit the activity of the CYP 2C9 human hepatic
P450 enzyme. Phenytoin is known to cause osteomalacia. No formal clinical studies have been conducted to assess if
there is an interactive effect on bone loss between phenytoin and Accutane. Therefore, caution should be exercised
when using these drugs together.
· Systemic Corticosteroids: Systemic corticosteroids are known
to cause osteoporosis. No formal clinical studies have been conducted to assess if there is an interactive effect on
bone loss between systemic corticosteroids and Accutane. Therefore, caution should be exercised when using these
drugs together.
Prescribers are advised to consult the package insert of medication administered concomitantly with
hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products.
Accutane use is associated with depression in some patients. Patients should be prospectively cautioned not to
self-medicate with the herbal supplement St. Johnís Wort because a possible interaction has been suggested
with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting
St. John's Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form
of St. John's Wort.
Laboratory Tests
Pregnancy Test
Female patients of childbearing potential must have negative results from 2 urine or serum pregnancy
tests with a sensitivity of at least 25 mIU/mL before receiving the initial Accutane prescription. The first test is
obtained by the prescriber when the decision is made to pursue qualification of the patient for Accutane (a screening
test). The second pregnancy test (a confirmation test) should be done during the first 5 days of the menstrual period
immediately preceding the beginning of Accutane therapy. For patients with amenorrhea, the second test should be done
at least 11 days after the last act of unprotected sexual intercourse (without using 2 effective forms of
contraception).
Each month of therapy, the patient must have a negative result from a urine or serum pregnancy test. A
pregnancy test must be repeated each month prior to the female patient receiving each prescription.
· Lipids: Pretreatment and follow-up blood lipids should be
obtained under fasting conditions. After consumption of alcohol, at least 36 hours should elapse before these
determinations are made. It is recommended that these tests be performed at weekly or biweekly intervals until the
lipid response to Accutane is established. The incidence of hypertriglyceridemia is 1 patient in 4 on Accutane
therapy.
· Liver Function Tests: Since elevations of liver enzymes have
been observed during clinical trials, and hepatitis has been reported, pretreatment and follow-up liver function
tests should be performed at weekly or biweekly intervals until the response to Accutane has been established.
· Glucose: Some patients receiving Accutane have experienced
problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during Accutane
therapy, although no causal relationship has been established.
· CPK: Some patients undergoing vigorous physical activity
while on Accutane therapy have experienced elevated CPK levels; however, the clinical significance is unknown. There
have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity. In a
clinical trial of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne, transient elevations
in CPK were observed in 12% of patients, including those undergoing strenuous physical activity in association with
reported musculoskeletal adverse events such as back pain, arthralgia, limb injury, or muscle sprain. In these
patients, approximately half of the CPK elevations returned to normal within 2 weeks and half returned to normal
within 4 weeks. No cases of rhabdomyolysis were reported in this trial.
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