Complete side effect information about accutane.
One should read this before decided to go on this drug.

Allergic Reactions: Accutane is contraindicated in patients who are
hypersensitive to this medication or to any of its components. Accutane should
not be given to patients who are sensitive to parabens, which are used as
preservatives in the gelatin capsule (see PRECAUTIONS: Hypersensitivity).

WARNINGS: Psychiatric Disorders: Accutane may cause depression, psychosis and,
rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of
Accutane therapy may be insufficient; further evaluation may be necessary. No
mechanism of action has been established for these events (see ADVERSE
REACTIONS: Psychiatric).
Pseudotumor Cerebri: Accutane use has been associated with a number of cases of
pseudotumor 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 to discontinue 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 been reported. 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 upon
cessation of Accutane therapy. Some patients have been able to reverse
triglyceride elevation by 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 high risk 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
are unknown. Animal Studies: In rats given 8 or 32 mg/kg/day of isotretinoin
(0.7 or 2.7 times the maximum clinical dose 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 a dosage of 60 to 120 mg/kg/day (15 to 30 times the maximum
clinical dose, respectively, after normalization for total body surface area).

Hearing Impairment: Impaired hearing has been reported in patients taking
Accutane; in some cases, 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 experience tinnitus or hearing
impairment should discontinue Accutane treatment and be referred to specialized
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 some instances, 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).

Skeletal: Hyperostosis: A high prevalence of skeletal hyperostosis was noted in
clinical trials for disorders of keratinization with a mean dose of 2.24
mg/kg/day. Additionally, skeletal hyperostosis was noted 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 in
prospective studies of nodular acne patients treated with a single course of
therapy at recommended doses. The skeletal effects of multiple Accutane
treatment courses for acne are unknown.

Premature Epiphyseal Closure: There are spontaneous reports of premature
epiphyseal closure in acne patients receiving recommended doses, but it is not
known if there is a causal relationship with Accutane. In clinical trials for
disorders of keratinization with a mean dose of 2.24 mg/kg/day, two children
showed x-ray findings suggestive of premature epiphyseal closure. The skeletal
effects of multiple Accutane treatment courses for acne are 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 and more 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 discontinuation of
the drug (see ADVERSE REACTIONS: Special Senses).

Decreased Night Vision: Decreased night vision has been reported during Accutane
therapy and in some instances the event has persisted after therapy was
discontinued. Because the onset in some 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: Information for Patients and Prescribers: Females of childbearing
potential should be instructed that they must not be pregnant when Accutane
therapy is initiated, and that they should use effective contraception 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
instructed to join the Accutane Survey and to review the patient videotape
provided by Roche to the prescriber that provides information about
contraception, the most common reasons that contraception fails, and the
importance of using effective contraception when taking teratogenic drugs.
Female patients should also be seen monthly and have a urine or serum pregnancy
test performed each month during treatment to confirm negative pregnancy status
CONTRAINDICATIONS AND WARNINGS).

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

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

. 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 of scarring (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 a clinical 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 some cases
persisted (see ADVERSE REACTIONS: Musculoskeletal).

. 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 been reported. Severe allergic
reaction necessitates discontinuation of therapy and appropriate medical
management.

Drug Interactions:

. 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.

. 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.

. Microdosed progesterone preparations (minipills) 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 oral contraceptives, as well 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 is
critically important that women of childbearing potential use two effective
forms of contraception simultaneously, unless absolute abstinence is the chosen
method, even when one of the forms is a hormonal contraceptive method (see boxed
CONTRAINDICATIONS AND WARNINGS).

Laboratory Tests:

. Pregnancy Test: Female patients of childbearing potential must have
negative results from two urine or serum pregnancy tests with a sensitivity of
at least 50 mIU/mL before a prescription is given. The first test is to be
performed at the office visit when the patient is qualified for Accutane therapy
by her prescriber. The second test is to be performed on the second day of her
next menstrual cycle or 11 days after her last unprotected act of sexual
intercourse, whichever is later. Additional pregnancy tests are to be conducted
monthly during treatment.

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

. Glucose: Some patients receiving Accutane have experienced problems in
the control of their blood sugar. In addition, new cases of diabetes have been
diagnosed during Accutane therapy, although no causal relationship has been
established.

. CPK: Some patients undergoing vigorous physical activity while on
Accutane therapy have experienced elevated CPK levels; however, the clinical
significance is unknown.

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 (0.7 or
2.7 times the maximum clinical dose, 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 the higher 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 with metabolic activation. No
dose-response effect was seen and all other strains were negative. Additionally,
other tests designed to assess genotoxicity (Chinese hamster cell assay, mouse
micronucleus 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 (0.2, 0.7, or 2.7 times the maximum clinical dose, respectively,
after normalization for total body surface 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 (5 or 15 times the
maximum clinical dose, 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 50 men (ages 17 to 32 years) receiving Accutane
(isotretinoin) therapy for nodular acne, no significant effects were seen 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 the potential for adverse effects, nursing mothers should not receive
Accutane.

ADVERSE REACTIONS: Clinical Trials and Postmarketing Surveillance: The adverse
reactions listed below reflect the experience from investigational studies of
Accutane, and the postmarketing 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 are similar to those described in
patients taking very high doses of vitamin A (dryness of the skin and 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 (see PRECAUTIONS: 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, ileitis, nausea, other
nonspecific 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 for other
hematological parameters.

Musculoskeletal: skeletal hyperostosis, calcification of tendons and ligaments,
premature epiphyseal closure (see WARNINGS: Skeletal), mild to moderate
musculoskeletal symptoms including arthralgia (see PRECAUTIONS: Information for
Patients and Prescribers), transient pain in the chest (see PRECAUTIONS:
Information for Patients and Prescribers), elevations of CPK (see PRECAUTIONS:
Laboratory Tests), arthritis, tendonitis, other types of bone abnormalities

Neurological: pseudotumor cerebri (see WARNINGS: Pseudotumor Cerebri),
dizziness, drowsiness, headache, insomnia, lethargy, malaise, nervousness,
paresthesias, seizures, stroke, syncope, weakness

Psychiatric: suicidal ideation, suicide attempts, suicide, depression, psychosis
(see WARNINGS: Psychiatric Disorders), emotional instability

Of the patients reporting depression, some reported that the depression subsided
with discontinuation of therapy and recurred with reinstitution of therapy.

Reproductive System: abnormal menses

Respiratory: bronchospasms (with or without a history of asthma), respiratory
infection, voice alteration

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 of skin, 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 granulomastosis;
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),
nonspecific urogenital findings (see PRECAUTIONS: Laboratory 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 Patients and Prescribers), elevated sedimentation
rates, elevated platelet counts, thrombocytopenia

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 (>300 times the maximum clinical dose after normalization of the rat dose
for total body surface area and >150 times the maximum clinical dose after
normalization of the mouse dose for total body surface area) and is
approximately 1960 mg/kg in rabbits (327 times the maximum clinical dose 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.

DOSAGE AND ADMINISTRATION: The recommended dosage range for Accutane is 0.5 to 2
mg/kg given in 2 divided doses daily for 15 to 20 weeks. In studies comparing
0.1, 0.5, and 1 mg/kg/day,8 it was found that all dosages provided initial
clearing of disease, but there was a greater need for retreatment with the lower
dosages.

It is recommended that for most patients the initial dosage of Accutane be 0.5
to 1 mg/kg/day. Patients whose disease is very severe or is primarily manifested
on the trunk may require up to the maximum recommended dosage, 2 mg/kg/day.
During treatment, the dose may be adjusted according to response of the disease
and/or the appearance of clinical side effects - some of which may be dose
related.

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 if warranted by persistent or recurring severe
nodular acne, a second course of therapy may be initiated. The optimal interval
before retreatment has not been defined for patients who have not completed
skeletal growth (see WARNINGS: Skeletal: Hyperostosis and Premature Epiphyseal
Closure).

Contraceptive measures must be followed for any subsequent course of therapy
(see boxed CONTRAINDICATIONS AND WARNINGS).

Accutane should be administered with food.




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