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ACCUTANE(isotretinoin)
CAPSULESCAUSES BIRTH DEFECTS

DO NOT GET PREGNANT
CONTRAINDICATIONS AND WARNINGS: Accutane must not be used byfemales who are pregnant. Although not every fetus exposed to Accutane has
resulted in a deformed child, there is an extremely high risk that a deformed infant
can result if pregnancy occurs while taking Accutane in any amount even for shortperiods of time. Potentially any fetus exposed during pregnancy can be affected.
Presently, there are no accurate means of determining, after Accutane exposure,which fetus has been affected and which fetus has not been affected.
Major human fetal abnormalities related to Accutane administration in females
have been documented. There is an increased risk of spontaneous abortion. In
addition, premature births have been reported.
Documented external abnormalities include: skull abnormality; ear abnormalities(including anotia, micropinna, small or absent external auditory canals); eyeabnormalities (including microphthalmia); facial dysmorphia; cleft palate.
Documented internal abnormalities include: CNS abnormalities (including cerebral
abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve
deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid
hormone deficiency. In some cases death has occurred with certain of theabnormalities previously noted.
Cases of IQ scores less than 85 with or without obvious CNS abnormalities have also
been reported.
Accutane is contraindicated in females of childbearing potential unless the patientThis label may not be the latest approved by FDA.
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meets all of the following conditions:•Must NOT be pregnant or breast feeding.

•Must be capable of complying with the mandatory contraceptive measuresrequired for Accutane therapy and understand behaviors associated with anincreased risk of pregnancy.

•

Must be reliable in understanding and carrying out instructions.
Accutane must be prescribed under the System to Manage Accutane Related
Teratogenicityää (S.M.A.R.T.ä
ä).
To prescribe Accutane, the prescriber must obtain a supply of yellow self-adhesive
Accutane Qualification Stickers. To obtain these stickers:

1) Read the booklet entitled System to Manage Accutane Related Teratogenicity(S.M.A.R.T.) Guide to Best Practices.
2) Sign and return the completed S.M.A.R.T. Letter of Understanding containing thefollowing Prescriber Checklist:
•
•
•
•

•

I know the risk and severity of fetal injury/birth defects from Accutane
I know how to diagnose and treat the various presentations of acne
I know the risk factors for unplanned pregnancy and the effective measures foravoidance of unplanned pregnancy
It is the informed patient’s responsibility to avoid pregnancy during Accutane
therapy and for 1 month after stopping Accutane. To help patients have theknowledge and tools to do so: Before beginning treatment of female patients with
Accutane I will refer for expert, detailed pregnancy prevention counseling andprescribing, reimbursed by the manufacturer, OR I have the expertise to perform
this function and elect to do so
I understand, and will properly use throughout the Accutane treatment course,
the S.M.A.R.T. procedures for Accutane, including monthly pregnancy avoidancecounseling, pregnancy testing and use of the yellow self-adhesive Accutane
Qualification Stickers

3) To use the yellow self-adhesive Accutane Qualification Sticker: Accutane should
not be prescribed or dispensed to any patient (male or female) without a yellow
self-adhesive Accutane Qualification Sticker.

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For female patients, the yellow self-adhesive Accutane Qualification Sticker signifies
that she:•Must have had 2 negative urine or serum pregnancy tests with a sensitivity of atleast 25 mIU/mL before receiving the initial Accutane prescription. The first test
(a screening test) is obtained by the prescriber when the decision is made topursue qualification of the patient for Accutane. The second pregnancy test (aconfirmation test) should be done during the first 5 days of the menstrual period
immediately preceding the beginning of Accutane therapy. For patients withamenorrhea, 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 orserum pregnancy test. A pregnancy test must be repeated every month prior to
the female patient receiving each prescription. The manufacturer will makeavailable urine pregnancy test kits for female Accutane patients for the initial,
second and monthly testing during therapy.

•

Must have selected and have committed to use 2 forms of effective contraception
simultaneously, at least 1 of which must be a primary form, unless absoluteabstinence is the chosen method, or the patient has undergone a hysterectomy.
Patients must use 2 forms of effective contraception for at least 1 month prior toinitiation of Accutane therapy, during Accutane therapy, and for 1 month after
discontinuing Accutane therapy. Counseling about contraception and behaviors
associated with an increased risk of pregnancy must be repeated on a monthly
basis.
Effective forms of contraception include both primary and secondary forms ofcontraception. Primary forms of contraception include: tubal ligation, partner’s
vasectomy, intrauterine devices, birth control pills, andinjectable/implantable/insertable hormonal birth control products. Secondary
forms of contraception include diaphragms, latex condoms, and cervical caps; eachmust be used with a spermicide.
Any birth control method can fail. Therefore, it is critically important that womenof childbearing potential use 2 effective forms of contraception simultaneously. A
drug interaction that decreases effectiveness of hormonal contraceptives has notbeen entirely ruled out for Accutane. Although hormonal contraceptives arehighly effective, there have been reports of pregnancy from women who have usedoral contraceptives, as well as injectable/implantable contraceptive products.
These reports occurred while these patients were taking Accutane. These reports
are more frequent for women who use only a single method of contraception.

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Patients must receive written warnings about the rates of possible contraception
failure (included in patient education kits).
Prescribers are advised to consult the package insert of any medication
administered concomitantly with hormonal contraceptives, since some medications
may decrease the effectiveness of these birth control products. Patients should beprospectively cautioned not to self-medicate with the herbal supplement St. John’sWort 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 ofcombined hormonal contraceptives who also used some form of St. John's Wort(see PRECAUTIONS).
•

Must have signed a Patient Information/Consent form that contains warnings
about the risk of potential birth defects if the fetus is exposed to isotretinoin.

•Must have been informed of the purpose and importance of participating in the
Accutane Survey and have been given the opportunity to enroll (seePRECAUTIONS).
The yellow self-adhesive Accutane Qualification Sticker documents that the female
patient is qualified, and includes the date of qualification, patient gender, cut-off
date for filling the prescription, and up to a 30-day supply limit with no refills.
These yellow self-adhesive Accutane Qualification Stickers should also be used formale patients.
Table 1. Use of Pregnancy Tests and Accutane Qualification Stickers for Patients
Patient TypeAll Males
Females ofChildbearing
Potential

Pregnancy
Test
RequiredNo
Yes

Qualification Date
Date Prescription
WrittenDate ofConfirmatory
Negative Pregnancy
Test
Date Prescription
WrittenAccutane
Qualification
Sticker Necessary
Yes

Dispense Within
7 Days of
Qualification Date
Yes

Yes

Yes

Females* Not of
No
Yes
Yes
Childbearing
Potential*Females who have had a hysterectomy or who are postmenopausal are not considered to be ofchildbearing potential.

If a pregnancy does occur during treatment of a woman with Accutane, theThis label may not be the latest approved by FDA.
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prescriber and patient should discuss the desirability of continuing the pregnancy.
Prescribers are strongly encouraged to report all cases of pregnancy to Roche@ 1-800-526-6367 where a Roche Pregnancy Prevention Program Specialist will beavailable to discuss Roche pregnancy information, or prescribers may contact the
Food and Drug Administration MedWatch Program @ 1-800-FDA-1088.
Accutane should be prescribed only by prescribers who have demonstrated special
competence in the diagnosis and treatment of severe recalcitrant nodular acne, areexperienced in the use of systemic retinoids, have read the S.M.A.R.T. Guide to Best
Practices, signed and returned the completed S.M.A.R.T. Letter of Understanding,and obtained yellow self-adhesive Accutane Qualification Stickers. Accutane should
not be prescribed or dispensed without a yellow self-adhesive Accutane
Qualification Sticker.
INFORMATION FOR PHARMACISTS:
ACCUTANE MUST ONLY BE DISPENSED:•IN NO MORE THAN A 30-DAY SUPPLY•ONLY ON PRESENTATION OF AN ACCUTANE PRESCRIPTION WITH A
YELLOW SELF-ADHESIVE ACCUTANE QUALIFICATION STICKER•WRITTEN WITHIN THE PREVIOUS 7 DAYS•REFILLS REQUIRE A NEW PRESCRIPTION WITH A YELLOW SELFADHESIVE ACCUTANE QUALIFICATION STICKER•NO TELEPHONE OR COMPUTERIZED PRESCRIPTIONS AREPERMITTED.
AN ACCUTANE MEDICATION GUIDE MUST BE GIVEN TO THE PATIENTEACH TIME ACCUTANE IS DISPENSED, AS REQUIRED BY LAW. THISACCUTANE MEDICATION GUIDE IS AN IMPORTANT PART OF THE RISKMANAGEMENT PROGRAM FOR THE PATIENT.

DESCRIPTION: Isotretinoin, a retinoid, is available as Accutane in 10-mg, 20-mg and 40-mg
soft gelatin capsules for oral administration. Each capsule contains beeswax, butylatedhydroxyanisole, edetate disodium, hydrogenated soybean oil flakes, hydrogenated vegetable oil,and soybean oil. Gelatin capsules contain glycerin and parabens (methyl and propyl), with theThis label may not be the latest approved by FDA.
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following dye systems: 10 mg — iron oxide (red) and titanium dioxide; 20 mg — FD&C Red
No. 3, FD&C Blue No. 1, and titanium dioxide; 40 mg — FD&C Yellow No. 6, D&C Yellow
No. 10, and titanium dioxide.
Chemically, isotretinoin is 13-cis-retinoic acid and is related to both retinoic acid and retinol(vitamin A). It is a yellow to orange crystalline powder with a molecular weight of 300.44. The
structural formula is:

CLINICAL PHARMACOLOGY: Isotretinoin is a retinoid, which when administered inpharmacologic dosages of 0.5 to 1.0 mg/kg/day (see DOSAGE AND ADMINISTRATION),
inhibits sebaceous gland function and keratinization. The exact mechanism of action of
isotretinoin is unknown.
Nodular Acne: Clinical improvement in nodular acne patients occurs in association with areduction in sebum secretion. The decrease in sebum secretion is temporary and is related to thedose and duration of treatment with Accutane, and reflects a reduction in sebaceous gland size
and an inhibition of sebaceous gland differentiation.1
Pharmacokinetics: Absorption: Due to its high lipophilicity, oral absorption of isotretinoin isenhanced when given with a high-fat meal. In a crossover study, 74 healthy adult subjects
received a single 80 mg oral dose (2 x 40 mg capsules) of Accutane under fasted and fed
conditions. Both peak plasma concentration (Cmax) and the total exposure (AUC) of isotretinoin
were more than doubled following a standardized high-fat meal when compared with Accutane
given under fasted conditions (see Table 2 below). The observed elimination half-life wasunchanged. This lack of change in half-life suggests that food increases the bioavailability ofisotretinoin without altering its disposition. The time to peak concentration (Tmax) was also
increased with food and may be related to a longer absorption phase. Therefore, Accutane
capsules should always be taken with food (see DOSAGE AND ADMINISTRATION). Clinicalstudies have shown that there is no difference in the pharmacokinetics of isotretinoin between
patients with nodular acne and healthy subjects with normal skin.

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Accutane
2 x 40 mg
CapsulesFed*
FastedTable 2. Pharmacokinetic Parameters of Isotretinoin
Mean (%CV), N=74
Cmax
Tmax
AUC0-∞∞(ng/mL)(hr)(ng⋅⋅hr/mL)
10,004 (22%)
3,703 (46%)

862 (22%)301 (63%)

5.3 (77%)
3.2 (56%)

t1/2
(hr)
21 (39%)21 (30%)*Eating a standardized high-fat meal
Distribution: Isotretinoin is more than 99.9% bound to plasma proteins, primarily albumin.
Metabolism: Following oral administration of isotretinoin, at least three metabolites have been
identified in human plasma: 4-oxo-isotretinoin, retinoic acid (tretinoin), and 4-oxo-retinoic acid
(4-oxo-tretinoin). Retinoic acid and 13-cis-retinoic acid are geometric isomers and show
reversible interconversion. The administration of one isomer will give rise to the other.
Isotretinoin is also irreversibly oxidized to 4-oxo-isotretinoin, which forms its geometric isomer4-oxo-tretinoin.
After a single 80 mg oral dose of Accutane to 74 healthy adult subjects, concurrent
administration of food increased the extent of formation of all metabolites in plasma whencompared to the extent of formation under fasted conditions.
All of these metabolites possess retinoid activity that is in some in vitro models more than that ofthe parent isotretinoin. However, the clinical significance of these models is unknown. After
multiple oral dose administration of isotretinoin to adult cystic acne patients (≥18 years), theexposure of patients to 4-oxo-isotretinoin at steady-state under fasted and fed conditions wasapproximately 3.4 times higher than that of isotretinoin.
In vitro studies indicate that the primary P450 isoforms involved in isotretinoin metabolism are
2C8, 2C9, 3A4, and 2B6. Isotretinoin and its metabolites are further metabolized into conjugates,
which are then excreted in urine and feces.
Elimination: Following oral administration of an 80 mg dose of 14C-isotretinoin as a liquidsuspension, 14C-activity in blood declined with a half-life of 90 hours. The metabolites ofisotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equalamounts (total of 65% to 83%). After a single 80 mg oral dose of Accutane to 74 healthy adultsubjects under fed conditions, the mean ± SD elimination half-lives (t1/2) of isotretinoin and 4oxo-isotretinoin were 21.0 ± 8.2 hours and 24.0 ± 5.3 hours, respectively. After both single andmultiple doses, the observed accumulation ratios of isotretinoin ranged from 0.90 to 5.43 inpatients with cystic acne.

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Special Patient Populations: Pediatric Patients: The pharmacokinetics of isotretinoin were
evaluated after single and multiple doses in 38 pediatric patients (12 to 15 years) and 19 adultpatients (≥18 years) who received Accutane for the treatment of severe recalcitrant nodular acne.
In both age groups, 4-oxo-isotretinoin was the major metabolite; tretinoin and 4-oxo-tretinoin
were also observed. The dose-normalized pharmacokinetic parameters for isotretinoin following
single and multiple doses are summarized in Table 3 for pediatric patients. There were no
statistically significant differences in the pharmacokinetics of isotretinoin between pediatric andadult patients.
Table 3. Pharmacokinetic Parameters of Isotretinoin Following Single and Multiple Dose
Administration in Pediatric Patients, 12 to 15 Years of Age
Mean (±± SD), N=38*
Isotretinoin
Isotretinoin(Single Dose)(Steady-State)
Cmax (ng/mL)
573.25 (278.79)
731.98 (361.86)
3033.37(1394.17)
5082.00(2184.23)
AUC(0-12) (ng⋅hr/mL)
6003.81 (2885.67)–
AUC(0-24) (ng⋅hr/mL)
Tmax (hr)†6.00 (1.00-24.60)
4.00 (0-12.00)
Cssmin (ng/mL)–
352.32 (184.44)
T1/2 (hr)–15.69 (5.12)
CL/F (L/hr)–
17.96 (6.27)*The single and multiple dose data in this table were obtained following a non-standardized mealthat is not comparable to the high-fat meal that was used in the study in Table 2.
†Median (range)
Parameter

In pediatric patients (12 to 15 years), the mean ± SD elimination half-lives (t1/2) of isotretinoin
and 4-oxo-isotretinoin were 15.7 ± 5.1 hours and 23.1 ± 5.7 hours, respectively. The
accumulation ratios of isotretinoin ranged from 0.46 to 3.65 for pediatric patients.
INDICATIONS AND USAGE: Severe Recalcitrant Nodular Acne: Accutane is indicated forthe treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with adiameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” bydefinition,2 means “many” as opposed to “few or several” nodules. Because of significant
adverse effects associated with its use, Accutane should be reserved for patients with severe
nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In
addition, Accutane is indicated only for those females who are not pregnant, because Accutane
can cause severe birth defects (see boxed CONTRAINDICATIONS AND WARNINGS).
A single course of therapy for 15 to 20 weeks has been shown to result in complete andprolonged remission of disease in many patients.1,3,4 If a second course of therapy is needed, itThis label may not be the latest approved by FDA.
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should not be initiated until at least 8 weeks after completion of the first course, because
experience has shown that patients may continue to improve while off Accutane. The optimal
interval before retreatment has not been defined for patients who have not completed skeletal
growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature
Epiphyseal Closure).
CONTRAINDICATIONS: Pregnancy: Category X. See boxed CONTRAINDICATIONS
AND WARNINGS.
Allergic Reactions: Accutane is contraindicated in patients who are hypersensitive to thismedication 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 (seePRECAUTIONS: Hypersensitivity).
WARNINGS: Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely,
suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors.
Discontinuation of Accutane therapy may be insufficient; further evaluation may benecessary. No mechanism of action has been established for these events (see ADVERSE
REACTIONS: Psychiatric). Prescribers should read the brochure, Recognizing Psychiatric
Disorders in Adolescents and Young Adults: A Guide for Prescribers of Accutaneââ(isotretinoin).
Pseudotumor Cerebri: Accutane use has been associated with a number of cases ofpseudotumor cerebri (benign intracranial hypertension), some of which involved
concomitant use of tetracyclines. Concomitant treatment with tetracyclines should
therefore be avoided. Early signs and symptoms of pseudotumor cerebri include
papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these
symptoms should be screened for papilledema and, if present, they should be told todiscontinue Accutane immediately and be referred to a neurologist for further diagnosis
and care (see ADVERSE REACTIONS: Neurological).
Pancreatitis: Acute pancreatitis has been reported in patients with either elevated or normal
serum triglyceride levels. In rare instances, fatal hemorrhagic pancreatitis has beenreported. Accutane should be stopped if hypertriglyceridemia cannot be controlled at an
acceptable level or if symptoms of pancreatitis occur.
Lipids: Elevations of serum triglycerides have been reported in patients treated with Accutane.
Marked elevations of serum triglycerides in excess of 800 mg/dL were reported in approximately
25% of patients receiving Accutane in clinical trials. In addition, approximately 15% developed
a decrease in high-density lipoproteins and about 7% showed an increase in cholesterol levels.
In clinical trials, the effects on triglycerides, HDL, and cholesterol were reversible uponcessation of Accutane therapy. Some patients have been able to reverse triglyceride elevation by

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reduction in weight, restriction of dietary fat and alcohol, and reduction in dose while continuing
Accutane.5
Blood lipid determinations should be performed before Accutane is given and then at intervals
until the lipid response to Accutane is established, which usually occurs within 4 weeks.
Especially careful consideration must be given to risk/benefit for patients who may be at highrisk during Accutane therapy (patients with diabetes, obesity, increased alcohol intake, lipid
metabolism disorder or familial history of lipid metabolism disorder). If Accutane therapy is
instituted, more frequent checks of serum values for lipids and/or blood sugar are recommended(see PRECAUTIONS: Laboratory Tests).
The cardiovascular consequences of hypertriglyceridemia associated with Accutane areunknown. Animal Studies: In rats given 8 or 32 mg/kg/day of isotretinoin (1.3 to 5.3 times therecommended clinical dose of 1.0 mg/kg/day after normalization for total body surface area) for
18 months or longer, the incidences of focal calcification, fibrosis and inflammation of the
myocardium, calcification of coronary, pulmonary and mesenteric arteries, and metastatic
calcification of the gastric mucosa were greater than in control rats of similar age. Focal
endocardial and myocardial calcifications associated with calcification of the coronary arteries
were observed in two dogs after approximately 6 to 7 months of treatment with isotretinoin at adosage of 60 to 120 mg/kg/day (30 to 60 times the recommended clinical dose of 1.0 mg/kg/day,
respectively, after normalization for total body surface area).
Hearing Impairment: Impaired hearing has been reported in patients taking Accutane; in somecases, the hearing impairment has been reported to persist after therapy has been discontinued.
Mechanism(s) and causality for this event have not been established. Patients who experiencetinnitus or hearing impairment should discontinue Accutane treatment and be referred forspecialized care for further evaluation (see ADVERSE REACTIONS: Special Senses).
Hepatotoxicity: Clinical hepatitis considered to be possibly or probably related to Accutane
therapy has been reported. Additionally, mild to moderate elevations of liver enzymes have been
observed in approximately 15% of individuals treated during clinical trials, some of which
normalized with dosage reduction or continued administration of the drug. If normalization does
not readily occur or if hepatitis is suspected during treatment with Accutane, the drug should be
discontinued and the etiology further investigated.
Inflammatory Bowel Disease: Accutane has been associated with inflammatory bowel disease(including regional ileitis) in patients without a prior history of intestinal disorders. In someinstances, symptoms have been reported to persist after Accutane treatment has been stopped.
Patients experiencing abdominal pain, rectal bleeding or severe diarrhea should discontinue
Accutane immediately (see ADVERSE REACTIONS: Gastrointestinal).

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Skeletal: Bone Mineral Density: Effects of multiple courses of Accutane on the developing
musculoskeletal system are unknown. There is some evidence that long-term, high-dose, or
multiple courses of therapy with isotretinoin have more of an effect than a single course oftherapy on the musculoskeletal system. In an open-label clinical trial (N=217) of a single courseof therapy with Accutane for severe recalcitrant nodular acne, bone density measurements atseveral skeletal sites were not significantly decreased (lumbar spine change >-4% and total hipchange >-5%) or were increased in the majority of patients. One patient had a decrease in
lumbar spine bone mineral density >4% based on unadjusted data. Sixteen (7.9%) patients had
decreases in lumbar spine bone mineral density >4%, and all the other patients (92%) did nothave significant decreases or had increases (adjusted for body mass index). Nine patients (4.5%)
had a decrease in total hip bone mineral density >5% based on unadjusted data. Twenty-one(10.6%) patients had decreases in total hip bone mineral density >5%, and all the other patients(89%) did not have significant decreases or had increases (adjusted for body mass index).
Follow-up studies performed in 8 of the patients with decreased bone mineral density for up to
11 months thereafter demonstrated increasing bone density in 5 patients at the lumbar spine,
while the other 3 patients had lumbar spine bone density measurements below baseline values.
Total hip bone mineral densities remained below baseline (range –1.6% to -7.6%) in 5 of 8
patients (62.5%).
In a separate open-label extension study of 10 patients, ages 13-18 years, who started a second
course of Accutane 4 months after the first course, two patients showed a decrease in mean
lumbar spine bone mineral density up to 3.25% (adjusted for body mass index).
Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone
fractures have been seen in the Accutane population. While causality to Accutane has not been
established, an effect cannot be ruled out. Longer term effects have not been studied. It is
important that Accutane be given at the recommended doses for no longer than the recommended
duration.
Hyperostosis: A high prevalence of skeletal hyperostosis was noted in clinical trials for disordersof keratinization with a mean dose of 2.24 mg/kg/day. Additionally, skeletal hyperostosis wasnoted in 6 of 8 patients in a prospective study of disorders of keratinization.6 Minimal skeletal
hyperostosis and calcification of ligaments and tendons have also been observed by x-ray inprospective studies of nodular acne patients treated with a single course of therapy atrecommended doses. The skeletal effects of multiple Accutane treatment courses for acne areunknown.
In a clinical study of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne,
hyperostosis was not observed after 16 to 20 weeks of treatment with approximately 1 mg/kg/dayof Accutane given in two divided doses. Hyperostosis may require a longer time frame toappear. The clinical course and significance remain unknown.

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Premature Epiphyseal Closure: There are spontaneous reports of premature epiphyseal closurein acne patients receiving recommended doses of Accutane. The effect of multiple courses of
Accutane on epiphyseal closure is unknown.
Vision Impairment: Visual problems should be carefully monitored. All Accutane patients
experiencing visual difficulties should discontinue Accutane treatment and have an
ophthalmological examination (see ADVERSE REACTIONS: Special Senses).
Corneal Opacities: Corneal opacities have occurred in patients receiving Accutane for acne andmore frequently when higher drug dosages were used in patients with disorders of keratinization.
The corneal opacities that have been observed in clinical trial patients treated with Accutane
have either completely resolved or were resolving at follow-up 6 to 7 weeks after discontinuationof the drug (see ADVERSE REACTIONS: Special Senses).
Decreased Night Vision: Decreased night vision has been reported during Accutane therapy andin some instances the event has persisted after therapy was discontinued. Because the onset insome patients was sudden, patients should be advised of this potential problem and warned to be
cautious when driving or operating any vehicle at night.
PRECAUTIONS: The Accutane Pregnancy Prevention and Risk Management Programs consistof the System to Manage Accutane Related Teratogenicity (S.M.A.R.T.) and the Accutane
Pregnancy Prevention Program (PPP). S.M.A.R.T. should be followed for prescribing Accutane
with the goal of preventing fetal exposure to isotretinoin. It consists of: 1) reading the booklet
entitled System to Manage Accutane Related Teratogenicity (S.M.A.R.T.) Guide to Best
Practices, 2) signing and returning the completed S.M.A.R.T. Letter of Understanding
containing the Prescriber Checklist, 3) a yellow self-adhesive Accutane Qualification Sticker tobe affixed to the prescription page. In addition, the patient educational material, Be Smart, Be
Safe, Be Sure, should be used with each patient.
The following further describes each component:

1) The S.M.A.R.T. Guide to Best Practices includes: Accutane teratogenic potential,
information on pregnancy testing, specific information about effective contraception, thelimitations of contraceptive methods and behaviors associated with an increased risk ofcontraceptive failure and pregnancy, the methods to evaluate pregnancy risk, and the method
to complete a qualified Accutane prescription.
2) The S.M.A.R.T. Letter of Understanding attests that Accutane prescribers understand that
Accutane is a teratogen, have read the S.M.A.R.T. Guide to Best Practices, understand their
responsibilities in preventing exposure of pregnant females to Accutane and the proceduresfor qualifying female patients as defined in the boxed CONTRAINDICATIONS ANDWARNINGS.

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The Prescriber Checklist attests that Accutane prescribers know the risk and severity of
injury/birth defects from Accutane; know how to diagnose and treat the various presentationsof acne; know the risk factors for unplanned pregnancy and the effective measures foravoidance; will refer the patient for, or provide, detailed pregnancy prevention counseling tohelp the patient have knowledge and tools needed to fulfill their ultimate responsibility to
avoid becoming pregnant; understand and properly use throughout the Accutane treatment
course, the revised risk management procedures, including monthly pregnancy avoidancecounseling, pregnancy testing, and use of qualified prescriptions with the yellow selfadhesive Accutane Qualification Sticker.
3) The yellow self-adhesive Accutane Qualification Sticker is used as documentation that theprescriber has qualified the female patient according to the qualification criteria (see boxed
CONTRAINDICATIONS AND WARNINGS).
4) Accutane Pregnancy Prevention Program (PPP) is a systematic approach to comprehensive
patient education about their responsibilities and includes education for contraception
compliance and reinforcement of educational messages. The PPP includes information on therisks and benefits of Accutane which is linked to the Accutane Medication Guide dispensedby pharmacists with each prescription.
Male and female patients are provided with separate booklets. Each booklet contains
information on Accutane therapy, including precautions and warnings, an Informed
Consent/Patient Agreement form, and a toll-free line which provides Accutane information in
13 languages.
The booklet for male patients, Be Smart, Be Safe, Be Sure, Accutane Risk Management
Program for Men, also includes information about male reproduction, a warning not to share
Accutane with others or to donate blood during Accutane therapy and for 1 month following
discontinuation of Accutane.
The booklet for female patients, Be Smart, Be Safe, Be Sure, Accutane Pregnancy Prevention
and Risk Management Program for Women, also includes a referral program that offers
females free contraception counseling, reimbursed by the manufacturer, by a reproductive
specialist; a second Patient Information/Consent form concerning birth defects, obtaining her
consent to be treated within this agreement; an enrollment form for the Accutane Survey; anda qualification checklist affirming the conditions under which female patients may receive
Accutane. In addition, there is information on the types of contraceptive methods, theselection and use of appropriate, effective contraception, and the rates of possible
contraceptive failure; a toll-free contraception counseling line; and a video about the mostcommon reasons for unplanned pregnancies.

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General: Although an effect of Accutane on bone loss is not established, physicians should use
caution when prescribing Accutane to patients with a genetic predisposition for age-related
osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders ofbone metabolism. This would include patients diagnosed with anorexia nervosa and those who
are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects
vitamin D metabolism, such as systemic corticosteroids and any anticonvulsant.
Patients may be at increased risk when participating in sports with repetitive impact where therisks of spondylolisthesis with and without pars fractures and hip growth plate injuries in earlyand late adolescence are known. There are spontaneous reports of fractures and/or delayed
healing in patients while on treatment with Accutane or following cessation of treatment with
Accutane while involved in these activities. While causality to Accutane has not been
established, an effect cannot be ruled out.
Information for Patients and Prescribers:•

Patients should be instructed to read the Medication Guide supplied as required by law when
Accutane is dispensed. The complete text of the Medication Guide is reprinted at the end of
this document. For additional information, patients should also read the Patient Product
Information, Important Information Concerning Your Treatment with Accutaneâ(isotretinoin). All patients should sign the Informed Consent/Patient Agreement.

•

Females of childbearing potential should be instructed that they must not be pregnant when
Accutane therapy is initiated, and that they should use 2 forms of effective contraception 1
month before starting Accutane, while taking Accutane, and for 1 month after Accutane has
been stopped. They should also sign a consent form prior to beginning Accutane therapy.
They should be given an opportunity to enroll in the Accutane Survey and to review thepatient videotape provided by the manufacturer to the prescriber. It includes information
about contraception, the most common reasons that contraception fails, and the importance ofusing 2 forms of effective contraception when taking teratogenic drugs. Female patientsshould be seen by their prescribers monthly and have a urine or serum pregnancy test
performed each month during treatment to confirm negative pregnancy status before anotherAccutane prescription is written (see boxed CONTRAINDICATIONS AND WARNINGS).

•

Accutane is found in the semen of male patients taking Accutane, but the amount delivered toa female partner would be about 1 million times lower than an oral dose of 40 mg. While theno-effect limit for isotretinoin-induced embryopathy is unknown, 20 years of postmarketing
reports include 4 with isolated defects compatible with features of retinoid exposed fetuses.
None of these cases had the combination of malformations characteristic of retinoid
exposure, and all had other possible explanations for the defects observed.

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Patients may report mental health problems or family history of psychiatric disorders. These reports should be
discussed with the patient and/or the patient’s family. A referral to a mental health professional may benecessary. The physician should consider whether or not Accutane therapy is appropriate in this setting (seeWARNINGS: Psychiatric).

•

Patients should be informed that they must not share Accutane with anyone else because of the risk of birthdefects and other serious adverse events.

•

Patients should not donate blood during therapy and for 1 month following discontinuance ofthe drug because the blood might be given to a pregnant woman whose fetus must not be
exposed to Accutane.

•

Patients should be reminded to take Accutane with a meal (see DOSAGE AND
ADMINISTRATION). To decrease the risk of esophageal irritation, patients should swallow
the capsules with a full glass of liquid.

•

Patients should be informed that transient exacerbation (flare) of acne has been seen,
generally during the initial period of therapy.

•

Wax epilation and skin resurfacing procedures (such as dermabrasion, laser) should be
avoided during Accutane therapy and for at least 6 months thereafter due to the possibility ofscarring (see ADVERSE REACTIONS: Skin and Appendages).

•

Patients should be advised to avoid prolonged exposure to UV rays or sunlight.

•

Patients should be informed that they may experience decreased tolerance to contact lenses
during and after therapy.

•

Patients should be informed that approximately 16% of patients treated with Accutane in aclinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In
general, these symptoms were mild to moderate, but occasionally required discontinuation of
the drug. Transient pain in the chest has been reported less frequently. In the clinical trial,
these symptoms generally cleared rapidly after discontinuation of Accutane, but in somecases persisted (see ADVERSE REACTIONS: Musculoskeletal). There have been rare
postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity(see Laboratory Tests: CPK).

•

Pediatric patients and their caregivers should be informed that approximately 29% (104/358)of pediatric patients treated with Accutane developed back pain. Back pain was severe in
13.5% (14/104) of the cases and occurred at a higher frequency in female than male patients.
Arthralgias were experienced in 22% (79/358) of pediatric patients. Arthralgias were severein 7.6% (6/79) of patients. Appropriate evaluation of the musculoskeletal system should bedone in patients who present with these symptoms during or after a course of Accutane.

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Consideration should be given to discontinuation of Accutane if any significant abnormality
is found.
•Neutropenia and rare cases of agranulocytosis have been reported. Accutane should be
discontinued if clinically significant decreases in white cell counts occur.

Hypersensitivity: Anaphylactic reactions and other allergic reactions have been reported.
Cutaneous allergic reactions and serious cases of allergic vasculitis, often with purpura (bruises
and red patches) of the extremities and extracutaneous involvement (including renal) have beenreported. Severe allergic reaction necessitates discontinuation of therapy and appropriate medical
management.
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, aswell as injectable/implantable contraceptive 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 iscritically important for women of childbearing potential to select and commit to use 2 formsof effective contraception simultaneously, at least 1 of which must be a primary form, unlessabsolute abstinence is the chosen method, or the patient has undergone a hysterectomy (seeboxed CONTRAINDICATIONS AND WARNINGS).

•

Phenytoin: Accutane has not been shown to alter the pharmacokinetics of phenytoin in astudy in seven healthy volunteers. These results are consistent with the in vitro finding thatneither isotretinoin nor its metabolites induce or inhibit the activity of the CYP 2C9 humanhepatic 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.

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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 boneloss between systemic corticosteroids and Accutane. Therefore, caution should be exercisedwhen using these drugs together.

Prescribers are advised to consult the package insert of medication administered concomitantlywith hormonal contraceptives, since some medications may decrease the effectiveness of thesebirth control products. Accutane use is associated with depression in some patients (seeWARNINGS: Psychiatric and ADVERSE REACTIONS: Psychiatric). Patients should beprospectively cautioned not to self-medicate with the herbal supplement St. John’s Wort because
a possible interaction has been suggested with hormonal contraceptives based on reports ofbreakthrough 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 theinitial Accutane prescription. The first test is obtained by the prescriber when the decision ismade 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 (see WARNINGS: Lipids).

•

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 shouldbe performed at weekly or biweekly intervals until the response to Accutane has been
established (see WARNINGS: Hepatotoxicity).

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Glucose: Some patients receiving Accutane have experienced problems in the control of theirblood 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 haveexperienced elevated CPK levels; however, the clinical significance is unknown. There havebeen rare postmarketing reports of rhabdomyolysis, some associated with strenuous physicalactivity. 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 thoseundergoing 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.

Carcinogenesis, Mutagenesis and Impairment of Fertility: In male and female Fischer 344 rats
given oral isotretinoin at dosages of 8 or 32 mg/kg/day (1.3 to 5.3 times the recommended
clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area) for
greater than 18 months, there was a dose-related increased incidence of pheochromocytoma
relative to controls. The incidence of adrenal medullary hyperplasia was also increased at thehigher dosage in both sexes. The relatively high level of spontaneous pheochromocytomas
occurring in the male Fischer 344 rat makes it an equivocal model for study of this tumor;
therefore, the relevance of this tumor to the human population is uncertain.
The Ames test was conducted with isotretinoin in two laboratories. The results of the tests in one
laboratory were negative while in the second laboratory a weakly positive response (less than 1.6
x background) was noted in S. typhimurium TA100 when the assay was conducted withmetabolic activation. No dose-response effect was seen and all other strains were negative.
Additionally, other tests designed to assess genotoxicity (Chinese hamster cell assay, mousemicronucleus test, S. cerevisiae D7 assay, in vitro clastogenesis assay with human-derived
lymphocytes, and unscheduled DNA synthesis assay) were all negative.
In rats, no adverse effects on gonadal function, fertility, conception rate, gestation or parturition
were observed at oral dosages of isotretinoin of 2, 8, or 32 mg/kg/day (0.3, 1.3, or 5.3 times therecommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total bodysurface area).
In dogs, testicular atrophy was noted after treatment with oral isotretinoin for approximately 30 weeks at dosages of
20 or 60 mg/kg/day (10 or 30 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after
normalization for total body surface area). In general, there was microscopic evidence for appreciable depression of
spermatogenesis but some sperm were observed in all testes examined and in no instance were completely atrophic
tubules seen. In studies of 66 men, 30 of whom were patients with nodular acne under treatment with oral
isotretinoin, no significant changes were noted in the count or motility of spermatozoa in the ejaculate. In a study ofThis label may not be the latest approved by FDA.
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50 men (ages 17 to 32 years) receiving Accutane (isotretinoin) therapy for nodular acne, no significant effects wereseen on ejaculate volume, sperm count, total sperm motility, morphology or seminal plasma fructose.

Pregnancy: Category X. See boxed CONTRAINDICATIONS AND WARNINGS.
Nursing Mothers: It is not known whether this drug is excreted in human milk. Because of thepotential for adverse effects, nursing mothers should not receive Accutane.
Pediatric Use: The use of Accutane in pediatric patients less than 12 years of age has not beenstudied. The use of Accutane for the treatment of severe recalcitrant nodular acne in pediatricpatients ages 12 to 17 years should be given careful consideration, especially for those patientswhere a known metabolic or structural bone disease exists (see PRECAUTIONS: General). Useof Accutane in this age group for severe recalcitrant nodular acne is supported by evidence froma clinical study comparing 103 pediatric patients (13 to 17 years) to 197 adult patients (≥18
years). Results from this study demonstrated that Accutane, at a dose of 1 mg/kg/day given in
two divided doses, was equally effective in treating severe recalcitrant nodular acne in both
pediatric and adult patients.
In studies with Accutane, adverse reactions reported in pediatric patients were similar to thosedescribed in adults except for the increased incidence of back pain and arthralgia (both of whichwere sometimes severe) and myalgia in pediatric patients (see ADVERSE REACTIONS).
In an open-label clinical trial (N=217) of a single course of therapy with Accutane for severe
recalcitrant nodular acne, bone density measurements at several skeletal sites were notsignificantly decreased (lumbar spine change >-4% and total hip change >-5%) or were increasedin the majority of patients. One patient had a decrease in lumbar spine bone mineral density>4% based on unadjusted data. Sixteen (7.9%) patients had decreases in lumbar spine bonemineral density >4%, and all the other patients (92%) did not have significant decreases or had
increases (adjusted for body mass index). Nine patients (4.5%) had a decrease in total hip bonemineral density >5% based on unadjusted data. Twenty-one (10.6%) patients had decreases intotal hip bone mineral density >5%, and all the other patients (89%) did not have significant
decreases or had increases (adjusted for body mass index). Follow-up studies performed in 8 of
the patients with decreased bone mineral density for up to 11 months thereafter demonstrated
increasing bone density in 5 patients at the lumbar spine, while the other 3 patients had lumbar
spine bone density measurements below baseline values. Total hip bone mineral densities
remained below baseline (range –1.6% to -7.6%) in 5 of 8 patients (62.5%).
Geriatric Use: Clinical studies of isotretinoin did not include sufficient numbers of subjects aged
65 years and over to determine whether they respond differently from younger subjects.
Although reported clinical experience has not identified differences in responses between elderly
and younger patients, effects of aging might be expected to increase some risks associated withisotretinoin therapy (see WARNINGS and PRECAUTIONS).

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ADVERSE REACTIONS: Clinical Trials and Postmarketing Surveillance: The adverse
reactions listed below reflect the experience from investigational studies of Accutane, and thepostmarketing experience. The relationship of some of these events to Accutane therapy is
unknown. Many of the side effects and adverse reactions seen in patients receiving Accutane aresimilar to those described in patients taking very high doses of vitamin A (dryness of the skinand mucous membranes, eg, of the lips, nasal passage, and eyes).
Dose Relationship: Cheilitis and hypertriglyceridemia are usually dose related. Most adverse
reactions reported in clinical trials were reversible when therapy was discontinued; however,some persisted after cessation of therapy (see WARNINGS and ADVERSE REACTIONS).
Body as a Whole: allergic reactions, including vasculitis, systemic hypersensitivity (seePRECAUTIONS: Hypersensitivity), edema, fatigue, lymphadenopathy, weight loss
Cardiovascular: palpitation, tachycardia, vascular thrombotic disease, stroke
Endocrine/Metabolic: hypertriglyceridemia (see WARNINGS: Lipids), alterations in blood sugar
levels (see PRECAUTIONS: Laboratory Tests)
Gastrointestinal: inflammatory bowel disease (see WARNINGS: Inflammatory Bowel Disease),
hepatitis (see WARNINGS: Hepatotoxicity), pancreatitis (see WARNINGS: Lipids), bleeding
and inflammation of the gums, colitis, esophagitis/esophageal ulceration, ileitis, nausea, othernonspecific gastrointestinal symptoms
Hematologic: allergic reactions (see PRECAUTIONS: Hypersensitivity), anemia,
thrombocytopenia, neutropenia, rare reports of agranulocytosis (see PRECAUTIONS:
Information for Patients and Prescribers). See PRECAUTIONS: Laboratory Tests for otherhematological parameters.
Musculoskeletal: skeletal hyperostosis, calcification of tendons and ligaments, prematureepiphyseal closure, decreases in bone mineral density (see WARNINGS: Skeletal),musculoskeletal symptoms (sometimes severe) including back pain and arthralgia (seePRECAUTIONS: Information for Patients and Prescribers), transient pain in the chest (seePRECAUTIONS: Information for Patients and Prescribers), arthritis, tendonitis, other types ofbone abnormalities, elevations of CPK/rare reports of rhabdomyolysis (see PRECAUTIONS:
Laboratory Tests)
Neurological: pseudotumor cerebri (see WARNINGS: Pseudotumor Cerebri), dizziness,
drowsiness, headache, insomnia, lethargy, malaise, nervousness, paresthesias, seizures, stroke,
syncope, weakness

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Psychiatric: suicidal ideation, suicide attempts, suicide, depression, psychosis, aggression,
violent behaviors (see WARNINGS: Psychiatric Disorders), emotional instability
Of the patients reporting depression, some reported that the depression subsided withdiscontinuation of therapy and recurred with reinstitution of therapy.
Reproductive System: abnormal menses
Respiratory: bronchospasms (with or without a history of asthma), respiratory infection, voicealteration
Skin and Appendages: acne fulminans, alopecia (which in some cases persists), bruising, cheilitis(dry lips), dry mouth, dry nose, dry skin, epistaxis, eruptive xanthomas,7 flushing, fragility ofskin, hair abnormalities, hirsutism, hyperpigmentation and hypopigmentation, infections(including disseminated herpes simplex), nail dystrophy, paronychia, peeling of palms and soles,
photoallergic/photosensitizing reactions, pruritus, pyogenic granuloma, rash (including facial
erythema, seborrhea, and eczema), sunburn susceptibility increased, sweating, urticaria,
vasculitis (including Wegener’s granulomatosis; see PRECAUTIONS: Hypersensitivity),
abnormal wound healing (delayed healing or exuberant granulation tissue with crusting; see
PRECAUTIONS: Information for Patients and Prescribers)
Special Senses: Hearing: hearing impairment (see WARNINGS: Hearing Impairment), tinnitus.
Vision: corneal opacities (see WARNINGS: Corneal Opacities), decreased night vision which
may persist (see WARNINGS: Decreased Night Vision), cataracts, color vision disorder,
conjunctivitis, dry eyes, eyelid inflammation, keratitis, optic neuritis, photophobia, visual
disturbances
Urinary System: glomerulonephritis (see PRECAUTIONS: Hypersensitivity), nonspecificurogenital findings (see PRECAUTIONS: Laboratory Tests for other urological parameters)
Laboratory: Elevation of plasma triglycerides (see WARNINGS: Lipids), decrease in serum
high-density lipoprotein (HDL) levels, elevations of serum cholesterol during treatment
Increased alkaline phosphatase, SGOT (AST), SGPT (ALT), GGTP or LDH (see WARNINGS:
Hepatotoxicity)
Elevation of fasting blood sugar, elevations of CPK (see PRECAUTIONS: Laboratory Tests),
hyperuricemia
Decreases in red blood cell parameters, decreases in white blood cell counts (including severe
neutropenia and rare reports of agranulocytosis; see PRECAUTIONS: Information for Patientsand Prescribers), elevated sedimentation rates, elevated platelet counts, thrombocytopenia

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White cells in the urine, proteinuria, microscopic or gross hematuria
OVERDOSAGE: The oral LD50 of isotretinoin is greater than 4000 mg/kg in rats and mice(>600 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the rat dose
for total body surface area and >300 times the recommended clinical dose of 1.0 mg/kg/day after
normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in
rabbits (653 times the recommended clinical dose of 1.0 mg/kg/day after normalization for total
body surface area). In humans, overdosage has been associated with vomiting, facial flushing,cheilosis, abdominal pain, headache, dizziness, and ataxia. All symptoms quickly resolved
without apparent residual effects.
Accutane causes serious birth defects at any dosage (see boxed CONTRAINDICATIONS ANDWARNINGS). Females of childbearing potential who present with isotretinoin overdose must be
evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to
the fetus, as described in the boxed CONTRAINDICATIONS AND WARNINGS. Non-pregnant
patients must be warned to avoid pregnancy for at least one month and receive contraceptive
counseling as described in the boxed CONTRAINDICATIONS AND WARNINGS. Educational
materials for such patients can be obtained by calling the manufacturer. Because an overdose
would be expected to result in higher levels of isotretinoin in semen than found during a normal
treatment course, male patients should use a condom, or avoid reproductive sexual activity with afemale who is or might become pregnant, for 30 days after the overdose. All patients withisotretinoin overdose should not donate blood for at least 30 days.
DOSAGE AND ADMINISTRATION: Accutane should be administered with a meal (seePRECAUTIONS: Information for Patients and Prescribers).
The recommended dosage range for Accutane is 0.5 to 1.0 mg/kg/day given in two divided doseswith food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1.0 mg/kg/day,8 it was foundthat all dosages provided initial clearing of disease, but there was a greater need for retreatment
with the lower dosages. During treatment, the dose may be adjusted according to response of thedisease and/or the appearance of clinical side effects — some of which may be dose related.
Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk
may require dose adjustments up to 2.0 mg/kg/day, as tolerated. Failure to take Accutane withfood will significantly decrease absorption. Before upward dose adjustments are made, thepatients should be questioned about their compliance with food instructions.
The safety of once daily dosing with Accutane has not been established. Once daily dosing is notrecommended.
If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks
of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, andThis label may not be the latest approved by FDA.
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if warranted by persistent or recurring severe nodular acne, a second course of therapy may beinitiated. The optimal interval before retreatment has not been defined for patients who have notcompleted skeletal growth. Long-term use of Accutane, even in low doses, has not been studied,and is not recommended. It is important that Accutane be given at the recommended doses forno longer than the recommended duration. The effect of long-term use of Accutane on bone loss
is unknown (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature
Epiphyseal Closure).
Contraceptive measures must be followed for any subsequent course of therapy (see boxed
CONTRAINDICATIONS AND WARNINGS).
Table 4. Accutane Dosing by Body Weight (Based on Administration With Food)
Body Weight
Total mg/day
kilograms
pounds
0.5 mg/kg
1 mg/kg
2 mg/kg*
40
88
20
40
80
50
110
25
50
100
60
132
30
60
120
70
154
35
70
140
80
176
40
80
160
90
198
45
90
180
100
220
50
100
200
*See DOSAGE AND ADMINISTRATION: the recommended dosage range is 0.5 to
1.0 mg/kg/day.
Information for Pharmacists: Accutane must only be dispensed in no more than a 30-day
supply and only on presentation of an Accutane prescription with a yellow self-adhesive
Accutane Qualification Sticker written within the previous 7 days. REFILLS REQUIRE A
NEW WRITTEN PRESCRIPTION WITH A YELLOW SELF-ADHESIVE ACCUTANEQUALIFICATION STICKER WITHIN THE PREVIOUS 7 DAYS. No telephone orcomputerized prescriptions are permitted.
An Accutane Medication Guide must be given to the patient each time Accutane is dispensed, as
required by law. This Accutane Medication Guide is an important part of the risk management
program for the patient.
HOW SUPPLIED: Soft gelatin capsules, 10 mg (light pink), imprinted ACCUTANE 10
ROCHE. Boxes of 100 containing 10 Prescription Paks of 10 capsules (NDC 0004-0155-49).

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Soft gelatin capsules, 20 mg (maroon), imprinted ACCUTANE 20 ROCHE. Boxes of 100
containing 10 Prescription Paks of 10 capsules (NDC 0004-0169-49).
Soft gelatin capsules, 40 mg (yellow), imprinted ACCUTANE 40 ROCHE. Boxes of 100
containing 10 Prescription Paks of 10 capsules (NDC 0004-0156-49).
Store at controlled room temperature (59° to 86°F, 15° to 30°C). Protect from light.
REFERENCES:
1. Peck GL, Olsen TG, Yoder FW, et al. Prolonged remissions of cystic and conglobate acnewith 13-cis-retinoic acid. N Engl J Med 300:329-333, 1979. 2. Pochi PE, Shalita AR, Strauss JS,
Webster SB. Report of the consensus conference on acne classification. J Am Acad Dermatol
24:495-500, 1991. 3. Farrell LN, Strauss JS, Stranieri AM. The treatment of severe cystic acnewith 13-cis-retinoic acid: evaluation of sebum production and the clinical response in a multipledose trial. J Am Acad Dermatol 3:602-611, 1980. 4. Jones H, Blanc D, Cunliffe WJ. 13-cisretinoic acid and acne. Lancet 2:1048-1049, 1980. 5. Katz RA, Jorgensen H, Nigra TP.
Elevation of serum triglyceride levels from oral isotretinoin in disorders of keratinization. Arch
Dermatol 116:1369-1372, 1980. 6. Ellis CN, Madison KC, Pennes DR, Martel W, Voorhees JJ.
Isotretinoin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol
10:1024-1029, 1984. 7. Dicken CH, Connolly SM. Eruptive xanthomas associated withisotretinoin (13-cis-retinoic acid). Arch Dermatol 116:951-952, 1980. 8. Strauss JS, Rapini RP,
Shalita AR, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J
Am Acad Dermatol 10:490-496, 1984.

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PATIENT INFORMATION/CONSENT (for female patients concerning birth defects):
To be completed by the patient, her parent/guardian*and signed by her prescriber.
Read each item below and initial in the space provided to show that you understand each item
and agree to follow your prescriber's instructions. Do not sign this consent and do not takeAccutane if there is anything that you do not understand.
*A parent or guardian of a minor patient (under age 18) must also read and initial each item
before signing the consent.
____________________________________________________________(Patient’s Name)

1. I understand that there is a very high risk that my unborn baby could have severe birthdefects if I am pregnant or become pregnant while taking Accutane in any amount even for
short periods of time. This is why I must not be pregnant while taking Accutane.
Initial: ______
2. I understand that I must not take Accutane (isotretinoin) if I am pregnant.
Initial: ______
3. I understand that I must not get pregnant during the entire time of my treatment and for 1
month after the end of my treatment with Accutane.
Initial: ________
4. I understand that I must avoid sexual intercourse completely, or I must use 2 separate,
effective forms of birth control (contraception) at the same time. The only exception is if I
have had surgery to remove the womb (a hysterectomy).
Initial: ________

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5. I understand that birth control pills and injectable/implantable/insertable hormonal birthcontrol products are among the most effective forms of birth control. However, any single
form of birth control can fail. Therefore, I must use 2 different methods at the same time,
every time I have sexual intercourse, even if 1 of the methods I choose is birth control pills or
injections.
Initial: ______
6. I will talk with my prescriber about any drugs or herbal products I plan to take during my
Accutane treatment because hormonal birth control methods (for example, birth control pills)
may not work if I am taking certain drugs or herbal products (for example, St. John’s Wort).
Initial: ______
7. I understand that the following are considered effective forms of birth control:
Primary:

Tubal ligation (tying my tubes), partner’s vasectomy, birth control pills,
injectable/implantable/insertable hormonal birth control products, and an IUD(intrauterine device).
Secondary: Diaphragms, latex condoms, and cervical caps. Each must be used with aspermicide, which is a special cream or jelly that kills sperm.
I understand that at least 1 of my 2 methods of birth control must be a primary method.
Initial: ________
8. I understand that I may receive a free contraceptive (birth control) counseling session andpregnancy testing from a doctor or other family planning expert. My Accutane prescriber cangive me an Accutane Patient Referral Form for this free consultation.
Initial: ______
9. I understand that I must begin using the birth control methods I have chosen as describedabove at least 1 month before I start taking Accutane.
Initial: ______
10. I understand that I cannot get a prescription for Accutane unless I have 2 negative pregnancy
test results. The first pregnancy test should be done when my prescriber decides to prescribe
Accutane. The second pregnancy test should be done during the first 5 days of my menstrual
period right before starting Accutane therapy, or as instructed by my prescriber. I will thenhave 1 pregnancy test every month during my Accutane therapy.
Initial: ______

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

11. I understand that I should not start taking Accutane until I am sure that I am not pregnant andhave negative results from 2 pregnancy tests.
Initial: ______
12. I have read and understand the materials my prescriber has given to me, including the Patient
Product Information, Important Information Concerning Your Treatment with Accutaneâ(isotretinoin). My prescriber gave me and asked me to watch the video about contraception. I
was told about a confidential counseling line that I may call for more information about birthcontrol. I have received information on emergency contraception (birth control).
Initial: ______
13. I understand that I must stop taking Accutane right away and inform my prescriber if I get
pregnant, miss my menstrual period, stop using birth control, or have sexual intercourse
without using my 2 birth control methods at any time.
Initial: ______
14. My prescriber gave me information about the confidential Accutane Survey and explained tome how important it is to take part in the Accutane Survey.
Initial: ______
15. I understand that the yellow self-adhesive Accutane Qualification Sticker on my prescription
for Accutane means that I am qualified to receive an Accutane prescription, because I:•

have had 2 negative urine or serum pregnancy tests before receiving the initial Accutane
prescription. I must have a negative result from a urine or serum pregnancy test repeated eachmonth prior to my receiving each subsequent prescription.

•

have selected and committed to use 2 forms of effective contraception simultaneously, atleast 1 of which must be a primary form, unless absolute abstinence is the chosen method, orI have undergone a hysterectomy. I must use 2 forms of contraception for at least 1 monthprior to initiation of Accutane therapy, during therapy, and for 1 month after discontinuingtherapy. I must receive counseling, repeated on a monthly basis, about contraception andbehaviors associated with an increased risk of pregnancy.

•

have signed a Patient Information/Consent form that contains warnings about the risk ofpotential birth defects if I am pregnant or become pregnant and my unborn baby is exposed
to isotretinoin.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda•

have been informed of the purpose and importance of participating in the Accutane Survey
and given the opportunity to enroll.
Initial: ______My prescriber has answered all my questions about Accutane and I understand that it is my
responsibility not to get pregnant during Accutane treatment or for 1 month after I stop taking
Accutane.
Initial: ______
I now authorize my prescriber ________________ to begin my treatment with Accutane.
Patient signature:________________________________ Date:____________________
Parent/guardian signature (if under age 18):____________________ Date:___________
Please print: Patient name and address______________________________________________________________________________ Telephone _______________________
I have fully explained to the patient, __________________, the nature and purpose of thetreatment described above and the risks to females of childbearing potential. I have asked thepatient if she has any questions regarding her treatment with Accutane and have answered thosequestions to the best of my ability.
Prescriber signature: ______________________________ Date:__________________

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

INFORMED CONSENT/PATIENT AGREEMENT (for all patients):
To be completed by patient (parent or guardian if patient is under age 18) and signed by the prescriber.

Read each item below and initial in the space provided if you understand each item andagree to follow your prescriber’s instructions. A parent or guardian of a patient under age
18 must also read and understand each item before signing the agreement.
Do not sign this agreement and do not take Accutane if there is anything that you do notunderstand about all the information you have received about using Accutane.
1. I, ____________________________________________________________,(Patient’s Name)
understand that Accutane is a medicine used to treat severe nodular acne that cannot becleared up by any other acne treatments, including antibiotics. In severe nodular acne, many
red, swollen, tender lumps form in the skin. If untreated, severe nodular acne can lead topermanent scars.
Initials: ______
2. My prescriber has told me about my choices for treating my acne.
Initials: ______
3. I understand that there are serious side effects that may happen while I am taking Accutane.
These have been explained to me. These side effects include serious birth defects in babies ofpregnant females. (Note: There is a second Informed Consent form for female patientsconcerning birth defects.)
Initials: ______

4. I understand that some patients, while taking Accutane or soonafter stopping Accutane, have become depressed or developed
other serious mental problems. Symptoms of these problems
include sad, “anxious” or empty mood, irritability, anger, loss ofpleasure or interest in social or sports activities, sleeping too
much or too little, changes in weight or appetite, school or work
performance going down, or trouble concentrating. Somepatients taking Accutane have had thoughts about hurtingthemselves or putting an end to their own lives (suicidal
thoughts). Some people tried to end their own lives. And somepeople have ended their own lives. There were reports that someof these people did not appear depressed. There have beenThis label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

reports of patients on Accutane becoming aggressive or violent.
No one knows if Accutane caused these behaviors or if theywould have happened even if the person did not take Accutane.
Some people have had other signs of depression while taking
Accutane (see #7 below).
Initials: ______

5. Before I start taking Accutane, I agree to tell my prescriber if,
to the best of my knowledge, I have ever had symptoms ofdepression (see #7 below), been psychotic, attempted suicide,
had any other mental problems, or take medicine for any ofthese problems. Being psychotic means having a loss of contact
with reality, such as hearing voices or seeing things that are notthere.
Initials: ______

6. Before I start taking Accutane, I agree to tell my prescriber if,
to the best of my knowledge, anyone in my family has ever had
symptoms of depression, been psychotic, attempted suicide, or
had any other serious mental problems.
Initials: ______
7. Once I start taking Accutane, I agree to stop using Accutane and tell my prescriber rightaway if any of the following happen. I:
•
•
•
•
•
•
•
•
•
•

Start to feel sad or have crying spells
Lose interest in activities I once enjoyedSleep too much or have trouble sleeping
Become more irritable, angry, or aggressive than usual (for example, temper outbursts,
thoughts of violence)
Have a change in my appetite or body weight
Have trouble concentrating
Withdraw from my friends or family
Feel like I have no energy
Have feelings of worthlessness or inappropriate guilt
Start having thoughts about hurting myself or taking my own life (suicidal thoughts)

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

Initials: ______
8. I agree to return to see my prescriber every month I take Accutane to get a newprescription for Accutane, to check my progress, and to check for signs of side effects.
Initials: ______
9. Accutane will be prescribed just for me—I will not share Accutane with other people
because it may cause serious side effects, including birth defects.
Initials: ______
10. I will not give blood while taking Accutane or for 1 month after I stop taking Accutane.
I understand that if someone who is pregnant gets my donated blood, her baby may be
exposed to Accutane and may be born with serious birth defects.
Initials: ______
11. I have read the Patient Product Information, Important Information Concerning Your
Treatment with Accutaneââ (isotretinoin), and other materials my provider gave me
containing important safety information about Accutane. I understand all theinformation I received.
Initials: ______
12. My prescriber and I have decided I should take Accutane. I understand that each of my
Accutane prescriptions must have a yellow self-adhesive Accutane Qualification Sticker
on it. I understand that I can stop taking Accutane at any time. I agree to tell myprescriber if I stop taking Accutane.
Initials: ______
I now authorize my prescriber ___________________________ to begin my treatment with
Accutane.
Patient Signature: __________________________________________ Date: _________
Parent/Guardian Signature (if under age 18): _____________________ Date: _________
Patient Name (print) ___________________________________
Patient address ____________________________________ Telephone (___.___.___)______________________________________

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

I have:••••fully explained to the patient, __________________, the nature and purpose of Accutane
treatment, including its benefits and risks
given the patient the appropriate educational materials, Be Smart, Be Safe, Be Sure, for
Accutane and asked the patient if he/she has any questions regarding his/her treatment with
Accutaneanswered those questions to the best of my ability
placed the yellow self-adhesive Accutane Qualification Sticker on the prescription.

Prescriber Signature: ___________________________________ Date:______________

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

MEDICATION GUIDE:
Read this Medication Guide every time you get a prescription or a refill for Accutane (ACK-u-tane). There may be
new information. This information does not take the place of talking with your prescriber (doctor or other healthcare provider).

What is the most important information I should know about Accutane?
Accutane is used to treat a type of severe acne (nodular acne) that has not been helped by othertreatments, including antibiotics. However, Accutane can cause serious side effects. Before
starting Accutane, discuss with your prescriber how bad your acne is, the possible benefits of
Accutane, and its possible side effects, to decide if Accutane is right for you. Your prescriber
will ask you to read and sign a form or forms indicating you understand some of the serious risksof Accutane.
Possible serious side effects of taking Accutane include birth defects and mental disorders.
1. Birth defects. Accutane can cause birth defects (deformed babies) if taken by apregnant woman. It can also cause miscarriage (losing the baby before birth),premature (early) birth, or death of the baby. Do not take Accutane if you are
pregnant or plan to become pregnant while you are taking Accutane. Do not get
pregnant for 1 month after you stop taking Accutane. Also, if you get pregnant while
taking Accutane, stop taking it right away and call your prescriber.
All females should read the section in this Medication Guide "What are theimportant warnings for females taking Accutane?"
2. Mental problems and suicide. Some patients, while taking Accutane or soon after
stopping Accutane, have become depressed or developed other serious mental
problems. Symptoms of these problems include sad, “anxious” or empty mood,irritability, anger, loss of pleasure or interest in social or sports activities, sleeping too
much or too little, changes in weight or appetite, school or work performance going
down, or trouble concentrating. Some patients taking Accutane have had thoughts
about hurting themselves or putting an end to their own lives (suicidal thoughts).
Some people tried to end their own lives. And some people have ended their own
lives. There were reports that some of these people did not appear depressed. There
have been reports of patients on Accutane becoming aggressive or violent. No one
knows if Accutane caused these behaviors or if they would have happened even if theperson did not take Accutane.
All patients should read the section in this Medication Guide "What are the signs

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

of mental problems?"
For other possible serious side effects of Accutane, see "What are the possible side
effects of Accutane?" in this Medication Guide.
What are the important warnings for females taking Accutane?
You must not become pregnant while taking Accutane, or for 1 month after you stop taking
Accutane. Accutane can cause severe birth defects in babies of women who take it while they are
pregnant, even if they take Accutane for only a short time. There is an extremely high risk thatyour baby will be deformed or will die if you are pregnant while taking Accutane. Taking
Accutane also increases the chance of miscarriage and premature births.
Female patients will not get their first prescription for Accutane unless there is proof they have
had 2 negative pregnancy tests. The first test must be done when your prescriber decides toprescribe Accutane. The second pregnancy test must be done during the first 5 days of themenstrual period right before starting Accutane therapy, or as instructed by your prescriber. Eachmonth of treatment, you must have a negative result from a urine or serum pregnancy test.
Female patients cannot get another prescription for Accutane unless there is proof that they have
had a negative pregnancy test.
A yellow self-adhesive Accutane Qualification Sticker on your prescription indicates to thepharmacist that you are qualified by your prescriber to get Accutane.
While you are taking Accutane, you must use effective birth control. You must use 2 separate
effective forms of birth control at the same time for at least 1 month before starting Accutane,
while you take it, and for 1 month after you stop taking it. You can either discuss effective birthcontrol methods with your prescriber or go for a free visit to discuss birth control with anotherphysician or family planning expert. Your prescriber can arrange this free visit, which will be
paid for by the manufacturer.
You must use 2 separate forms of effective birth control because any method, including birthcontrol pills and sterilization, can fail. There are only 2 reasons you would not need to use 2
separate methods of effective birth control:
1. You have had your womb removed by surgery (a hysterectomy).
2. You are absolutely certain you will not have genital-to-genital sexual contact with a malebefore, during, and for 1 month after Accutane treatment.
If you have sex at any time without using 2 forms of effective birth control, get pregnant, or
miss your period, stop using Accutane and call your prescriber right away.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

All patients should read the rest of this Medication Guide.
What are the signs of mental problems?
Tell your prescriber if, to the best of your knowledge, you or someone in your family has ever
had any mental illness, including depression, suicidal behavior, or psychosis. Psychosis means aloss of contact with reality, such as hearing voices or seeing things that are not there. Also, tell
your prescriber if you take medicines for any of these problems.
Stop using Accutane and tell your provider right away if you:
•
•
•
•
•
•
•
•
•
•

Start to feel sad or have crying spells
Lose interest in activities you once enjoyedSleep too much or have trouble sleeping
Become more irritable, angry, or aggressive than usual (for example, temper outbursts,
thoughts of violence)
Have a change in your appetite or body weight
Have trouble concentrating
Withdraw from your friends or family
Feel like you have no energy
Have feelings of worthlessness or inappropriate guilt
Start having thoughts about hurting yourself or taking your own life (suicidal thoughts)

What is Accutane?
Accutane is used to treat the most severe form of acne (nodular acne) that cannot be cleared up
by any other acne treatments, including antibiotics. In severe nodular acne, many red, swollen,tender lumps form in the skin. These can be the size of pencil erasers or larger. If untreated,
nodular acne can lead to permanent scars. However, because Accutane can have serious side
effects, you should talk with your prescriber about all of the possible treatments for your acne,
and whether Accutane’s possible benefits outweigh its possible risks.
Who should not take Accutane?
•

Do not take Accutane if you are pregnant, plan to become pregnant, or become
pregnant during Accutane treatment. Accutane causes severe birth defects. All females
should read the section “What are the important warnings for females taking Accutane?” formore information and warnings about Accutane and pregnancy.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda•

Do not take Accutane unless you completely understand its possible risks and are willing tofollow all of the instructions in this Medication Guide.

Tell your prescriber if you or someone in your family has had any kind of mental problems,
asthma, liver disease, diabetes, heart disease, osteoporosis (bone loss), weak bones, anorexia
nervosa (an eating disorder where people eat too little), or any other important health problems.
Tell your prescriber about any food or drug allergies you have had in the past. These problems
do not necessarily mean you cannot take Accutane, but your prescriber needs this information to
discuss if Accutane is right for you.
How should I take Accutane?
•
•

•
•

•
•

You will get no more than a 30-day supply of Accutane at a time, to be sure you check inwith your prescriber each month to discuss side effects.
Your prescription should have a special yellow self-adhesive sticker attached to it. The
sticker is YELLOW. If your prescription does not have this yellow self-adhesive sticker, callyour prescriber. The pharmacy should not fill your prescription unless it has the yellow selfadhesive sticker.
The amount of Accutane you take has been specially chosen for you and may change during
treatment.
You will take Accutane 2 times a day with a meal, unless your prescriber tells you otherwise.
Swallow your Accutane capsules with a full glass of liquid. This will help prevent the
medication inside the capsule from irritating the lining of your esophagus (connection
between mouth and stomach). For the same reason, do not chew or suck on the capsule.
If you miss a dose, just skip that dose. Do not take 2 doses the next time.
You should return to your prescriber as directed to make sure you don’t have signs of serious
side effects. Because some of Accutane’s serious side effects show up in blood tests, some ofthese visits may involve blood tests (monthly visits for female patients should always include
a urine or serum pregnancy test).

What should I avoid while taking Accutane?
•••

Do not get pregnant while taking Accutane. See “What is the most important information I
should know about Accutane?” and “What are the important warnings for females taking
Accutane?”
Do not breast feed while taking Accutane and for 1 month after stopping Accutane. We do
not know if Accutane can pass through your milk and harm the baby.
Do not give blood while you take Accutane and for 1 month after stopping Accutane. If
someone who is pregnant gets your donated blood, her baby may be exposed to Accutane andmay be born with birth defects.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

•
•

•
•
•

•
•
•

Do not take vitamin A supplements. Vitamin A in high doses has many of the same side
effects as Accutane. Taking both together may increase your chance of getting side effects.
Do not have cosmetic procedures to smooth your skin, including waxing, dermabrasion,or laser procedures, while you are using Accutane and for at least 6 months after you
stop. Accutane can increase your chance of scarring from these procedures. Check with yourprescriber for advice about when you can have cosmetic procedures.
Avoid sunlight and ultraviolet lights as much as possible. Tanning machines use ultraviolet
lights. Accutane may make your skin more sensitive to light.
Do not use birth control pills that do not contain estrogen (“minipills”). They may notwork while you take Accutane. Ask your prescriber or pharmacist if you are not sure what
type you are using.
Talk with your doctor if you plan to take other drugs or herbal products. This isespecially important for patients using birth control pills and other hormonal types of birthcontrol because the birth control may not work as effectively if you are taking certain drugs
or herbal products. You should not take the herbal supplement St. John’s Wort because thisherbal supplement may make birth control pills not work as effectively.
Talk with your doctor if you are currently taking an oral or injected corticosteroid or
anticonvulsant (seizure) medication prior to using Accutane. These drugs may weaken
your bones.
Do not share Accutane with other people. It can cause birth defects and other serious
health problems.
Do not take Accutane with antibiotics unless you talk to your prescriber. For some
antibiotics, you may have to stop taking Accutane until the antibiotic treatment is finished.
Use of both drugs together can increase the chances of getting increased pressure in the brain.

What are the possible side effects of Accutane?
Accutane has possible serious side effects•

Accutane can cause birth defects, premature births, and death in babies whose mothers
took Accutane while they were pregnant. See “What is the most important information I
should know about Accutane?” and “What are the important warnings for females taking
Accutane?”•

Serious mental health problems. See “What is the most important information I should
know about Accutane?”•

Serious brain problems. Accutane can increase the pressure in your brain. This can lead topermanent loss of sight, or in rare cases, death. Stop taking Accutane and call your prescriber
right away if you get any of these signs of increased brain pressure: bad headache, blurredThis label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

vision, dizziness, nausea, or vomiting. Also, some patients taking Accutane have had seizures(convulsions) or stroke.
•

Abdomen (stomach area) problems. Certain symptoms may mean that your internal organs
are being damaged. These organs include the liver, pancreas, bowel (intestines), andesophagus (connection between mouth and stomach). If your organs are damaged, they may
not get better even after you stop taking Accutane. Stop taking Accutane and call yourprescriber if you get severe stomach, chest or bowel pain, trouble swallowing or painful
swallowing, new or worsening heartburn, diarrhea, rectal bleeding, yellowing of your skin oreyes, or dark urine.

•

Bone and muscle problems. Accutane may affect bones, muscles, and ligaments and cause
pain in your joints or muscles. Tell your prescriber if you plan vigorous physical activity
during treatment with Accutane. Tell your prescriber if you develop pain, particularly backpain or joint pain. There are reports that some patients have had stunted growth after taking
Accutane for acne as directed. There are also some reports of broken bones or reduced
healing of broken bones after taking Accutane for acne as directed. No one knows if taking
Accutane for acne will affect your bones. If you have a broken bone, tell your provider thatyou are taking Accutane. Muscle weakness with or without pain can be a sign of serious
muscle damage. If this happens, stop taking Accutane and call your prescriber right away.

•

Hearing problems. Some people taking Accutane have developed hearing problems. It is
possible that hearing loss can be permanent. Stop using Accutane and call your prescriber if
your hearing gets worse or if you have ringing in your ears.

•

Vision problems. While taking Accutane you may develop a sudden inability to see in thedark, so driving at night can be dangerous. This condition usually clears up after you stoptaking Accutane, but it may be permanent. Other serious eye effects can occur. Stop taking
Accutane and call your prescriber right away if you have any problems with your vision or
dryness of the eyes that is painful or constant.

•

Lipid (fats and cholesterol in blood) problems. Many people taking Accutane develop highlevels of cholesterol and other fats in their blood. This can be a serious problem. Return toyour prescriber for blood tests to check your lipids and to get any needed treatment. These
problems generally go away when Accutane treatment is finished.

•

Allergic reactions. In some people, Accutane can cause serious allergic reactions. Stoptaking Accutane and get emergency care right away if you develop hives, a swollen face or
mouth, or have trouble breathing. Stop taking Accutane and call your prescriber if you
develop a fever, rash, or red patches or bruises on your legs.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda•

Signs of other possibly serious problems. Accutane may cause other problems. Tell yourprescriber if you have trouble breathing (shortness of breath), are fainting, are very thirsty or
urinate a lot, feel weak, have leg swelling, convulsions, slurred speech, problems moving, or
any other serious or unusual problems. Frequent urination and thirst can be signs of blood
sugar problems.

Serious permanent problems do not happen often. However, because the symptoms listed above
may be signs of serious problems, if you get these symptoms, stop taking Accutane and call yourprescriber. If not treated, they could lead to serious health problems. Even if these problems aretreated, they may not clear up after you stop taking Accutane.
Accutane has less serious possible side effects
The common less serious side effects of Accutane are dry skin, chapped lips, dry eyes, and drynose that may lead to nosebleeds. People who wear contact lenses may have trouble wearing
them while taking Accutane and after therapy. Sometimes, people’s acne may get worse for awhile. They should continue taking Accutane unless told to stop by their prescriber.
These are not all of Accutane’s possible side effects. Your prescriber or pharmacist can give you
more detailed information that is written for health care professionals.
This Medication Guide is only a summary of some important information about Accutane.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.
If you have any concerns or questions about Accutane, ask your prescriber. Do not use Accutane
for a condition for which it was not prescribed.
Active Ingredient: Isotretinoin.
Inactive Ingredients: beeswax, butylated hydroxyanisole, edetate disodium, hydrogenatedsoybean oil flakes, hydrogenated vegetable oil, and soybean oil. Gelatin capsules containglycerin and parabens (methyl and propyl), with the following dye systems: 10 mg — iron oxide(red) and titanium dioxide; 20 mg — FD&C Red No. 3, FD&C Blue No. 1, and titanium dioxide;
40 mg — FD&C Yellow No. 6, D&C Yellow No. 10, and titanium dioxide.
This Medication Guide has been approved by the U.S. Food and Drug Administration.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

Rx only

27898276-0602
Revised: June 2002
Printed in USA
Copyright © 2000-2002 by Roche Laboratories Inc. All rights reserved.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda[text printed on 'prescription pak' blister cards]

ALL PATIENTS:
It is important for your health that you read all the information you received
with this prescription and from your prescriberThis package provides reminders of important safety facts about Accutane, but it does notcontain all the information you need to know. It is important for you to know how to takeAccutane correctly and what side effects to watch for.
Read all the information you get about Accutane from your prescriber and pharmacist, including
the Medication Guide provided with this package.
The prescription you got at your prescriber's office should have had a special yellow selfadhesive sticker on it. The sticker is YELLOW. If your prescriptions for Accutane do not havethis yellow self-adhesive sticker, call your prescriber. The pharmacy should not fill prescriptions
for Accutane unless they have the yellow self-adhesive sticker.
You should read, understand and sign an Informed Consent/Patient Agreement before you takeAccutane. Contact your prescriber if you have not signed this form (male patients must sign one
form and female patients must sign two forms).

Never share Accutane because it can cause serious side effects
including severe birth defects.

Special Warning for Female Patients
CAUSES BIRTH DEFECTS

DO NOT GET PREGNANT

Accutane causes serious birth defects. Do NOT take Accutane if you are pregnant.
It is very important for you to read and understand the information about preventing
pregnancy on the back of this package, in the Medication Guide, and in the materials given
to you by your prescriber. If you do not have the Medication Guide, and a video and the Be

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

Smart, Be Safe, Be Sure booklet about pregnancy prevention, don’t start taking Accutane.
Call your prescriber.
Most people have further questions after reading so much important information about
pregnancy prevention and birth defects. If there is anything you are not sure about, do not takeAccutane until your questions have been answered by your prescriber.

Important Information for All Patients
Before you start taking Accutane, tell your prescriber if you:•

Are currently taking an oral or injected corticosteroid or an anticonvulsant (seizure)
medication.

•

Take part in sports where you are more likely to break a bone.

•

Have anorexia nervosa (a type of eating disorder), back pain, a history of problems withhealing of bone fractures, or problems with bone metabolism.

Mental problems and suicide
Some patients have become depressed or developed other serious mental problems while they
were taking Accutane or shortly after stopping Accutane. Some patients taking Accutane have
had thoughts of ending their own lives (suicidal thoughts). Some people have tried to end theirown lives (attempted suicide) and some people have ended their own lives (committed suicide).
There have been reports of patients on Accutane becoming aggressive or violent. No one knows
if Accutane caused these problems or behaviors or if they would have happened even if theperson did not take Accutane.
Stop taking Accutane and call your prescriber right away if you:•

Start to feel sad or have crying spells.

•

Lose interest in activities you once enjoyed.

•

Sleep too much or have trouble sleeping.

•

Become more irritable, angry, or aggressive than usual (for example, temper outbursts,
thoughts of violence)•

Have a change in your appetite or body weight.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda•

Have trouble concentrating.

•Withdraw from your friends or family.

•

Feel like you have no energy.

•

Have feelings of worthlessness or inappropriate guilt.

•

Start having thoughts about hurting yourself or taking your own life (suicidal thoughts).

Tell your prescriber if you or someone in your family has ever had a mental illness or if you takeany medicines for a mental illness (for example, depression).
Other serious side effects to watch for
Stop taking Accutane and call your prescriber if you develop any of the problems on thislist or any other unusual or severe problems. If not treated, they could lead to serious healthproblems. Serious permanent problems do not happen often.
•

Headaches, nausea, vomiting, blurred vision (increased brain pressure).

•

Severe stomach pain, diarrhea, rectal bleeding, or trouble swallowing.

•

Yellowing of your skin or eyes and/or dark urine.

•

Changes in hearing.

•Allergic reactions (if you know you are sensitive to “parabens”, tell your prescriber because
it is a preservative in the gelatin capsule of Accutane).

•

Bone or muscle pain.

•

Vision changes, including trouble seeing at night (this can start suddenly, so be very carefulwhen driving or operating any vehicle at night).

•

Persistent fever, chills, or sore throat.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

Other Important Information is found in the Medication Guide and in the booklet fromyour prescriber:•

Common side effects that are not serious but that you should tell your prescriber about.

•

How to take Accutane.

•

Things to avoid during Accutane treatment.

•

Ways to get more information if you need it.

Accutane Causes Serious Birth Defects[text appearing on main back panel outside of card]

Highlights of Warning to Female Patients. (It is important towatch the video and read all information in the Be Smart, Be Safe, Be
Sure booklet given to you by your prescriber.)•

You MUST NOT take Accutane if you are pregnant because any amount can cause severebirth defects, even for short periods during pregnancy.

•

You MUST NOT become pregnant while taking Accutane, or for 1 month after you stoptaking Accutane.

•

You will not get your first prescription for Accutane until there is proof you have had 2
negative pregnancy tests as instructed by your prescriber (a negative test means that it does
not show pregnancy).

•

You cannot get monthly refills for Accutane unless there is proof that you have had anegative pregnancy test every month during Accutane treatment.

•

Even the best methods of birth control can fail. Therefore, 2 separate, effective forms ofcontraception must be used at the same time for at least 1 month before beginning therapy,
during therapy, and for 1 month after Accutane therapy has stopped.

•

Stop taking Accutane right away and call your prescriber immediately if you have sex
without birth control, miss your period or become pregnant while you are taking Accutane. If
you get pregnant in the month after you have stopped Accutane treatment, call yourprescriber immediately.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

Very severe birth defects have occurred with Accutane use including:• Severe Internal Defects: defects that you cannot see—involving the brain (including lower IQ
scores), heart, glands and nervous system.
• Severe External Defects: defects that you can see—such as low-set, deformed or absent ears,
wide-set eyes, depressed bridge of nose, enlarged head and small chin.

[illustration of how to remove capsules]
Figure AStore at controlled room temperature (59° to 86°F, 15° to 30°C). Protect from light.

[binder copy]
FEMALE PATIENTS:
DO NOT GET PREGNANT
xxxxxxxx-xxxxxxxxxxxx-xxxx
xxxxxxxx-xxxx
Copyright © 2002 by Roche Laboratories Inc. All rights reserved.
Revised: June 2002

xx MG

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda--------------------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically andthis page is the manifestation of the electronic signature.
--------------------------------------------------------------------------------------------------------------------/s/--------------------Jonathan Wilkin
6/20/02 03:41:51 PM
minor formatting changes needed by sponsor in consent document