Sotret

Name: Sotret

What special precautions should I follow?

Before taking isotretinoin,

  • tell your doctor and pharmacist if you are allergic to isotretinoin, vitamin A, any other medications, or any of the ingredients in isotretinoin capsules. Ask your pharmacist or check the Medication Guide for a list of the inactive ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, herbal products, and nutritional supplements you are taking or plan to take. Be sure to mention medications for seizures such as phenytoin (Dilantin); medications for mental illness; oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone); tetracycline antibiotics such as demeclocycline (Declomycin), doxycycline (Monodox, Vibramycin, others), minocycline (Minocin, Vectrin), oxytetracycline (Terramycin), and tetracycline (Sumycin, Tetrex, others); and vitamin A supplements. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you or anyone in your family has thought about or attempted suicide and if you or anyone in your family has or has ever had depression, mental illness, diabetes, asthma, osteoporosis (a condition in which the bones are fragile and break easily), osteomalacia (weak bones due to a lack of vitamin D or difficulty absorbing this vitamin), or other conditions that cause weak bones, a high triglyceride (fats in the blood) level, a lipid metabolism disorder (any condition that makes it difficult for your body to process fats), anorexia nervosa (an eating disorder in which very little is eaten), or heart or liver disease. Also tell your doctor if you are overweight or if you drink or have ever drunk large amounts of alcohol.
  • do not breast-feed while you are taking isotretinoin and for 1 month after you stop taking isotretinoin.

  • plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Isotretinoin may make your skin sensitive to sunlight.
  • you should know that isotretinoin may cause changes in your thoughts, behavior, or mental health. Some patients who took isotretinoin have developed depression or psychosis (loss of contact with reality), have become violent, have thought about killing or hurting themselves, and have tried or succeeded in doing so. You or your family should call your doctor right away if you experience any of the following symptoms: anxiety,sadness, crying spells, loss of interest in activities you used to enjoy, poor performance at school or work, sleeping more than usual, difficulty falling asleep or staying asleep, irritability, anger, aggression, changes in appetite or weight, difficulty concentrating, withdrawing from friends or family, lack of energy, feelings of worthlessness or guilt, thinking about killing or hurting yourself, acting on dangerous thoughts, or hallucinations (seeing or hearing things that do not exist). Be sure that your family members know which symptoms are serious so that they can call the doctor if you are unable to seek treatment on your own.
  • you should know that isotretinoin may cause your eyes to feel dry and make wearing contact lenses uncomfortable during and after your treatment.
  • you should know that isotretinoin may limit your ability to see in the dark. This problem may begin suddenly at any time during your treatment and may continue after your treatment is stopped. Be very careful when you drive or operate machinery at night.
  • plan to avoid hair removal by waxing, laser skin treatments, and dermabrasion (surgical smoothing of the skin) while you are taking isotretinoin and for 6 months after your treatment. Isotretinoin increases the risk that you will develop scars from these treatments. Ask your doctor when you can safely undergo these treatments.
  • talk to your doctor before you participate in hard physical activity such as sports. Isotretinoin may cause the bones to weaken or thicken abnormally and may increase the risk of certain bone injuries in people who perform some types of physical activity. If you break a bone during your treatment, be sure to tell all your healthcare providers that you are taking isotretinoin.

Indications

Severe Recalcitrant Nodular Acne

Sotret (isotret (isotret (isotretinoin capsules) inoin capsules) inoin capsules) is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. "Severe," by definition,2 means "many" as opposed to "few or several" nodules. Because of significant adverse effects associated with its use. Sotret (isotret (isotret (isotretinoin capsules) inoin capsules) inoin capsules) should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Sotret (isotret (isotret (isotretinoin capsules) inoin capsules) inoin capsules) is indicated only for those female patients who are not pregnant, because Sotret 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 and prolonged remission of disease in many patients.1,3,4 If a second course of therapy is needed, it 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 isotret (isotret (isotret (isotretinoin capsules) inoin capsules) inoin capsules) inoin capsules. 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).

  • Acne (Pimples)

How should I take Sotret (isotretinoin)?

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Each prescription of isotretinoin must be filled within 7 days of the date it was written by your doctor. You will receive no more than a 30-day supply of isotretinoin at one time.

Always take isotretinoin with a full glass of water. Do not chew or suck on the capsule. Swallow it whole.

Take isotretinoin with food.

Use this medicine for the full prescribed length of time. Your acne may seem to get worse at first, but should then begin to improve.

While using isotretinoin, you may need frequent blood tests.

Never share this medicine with another person, even if they have the same symptoms you have.

Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

Skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Do not get pregnant

CONTRAINDICATIONS AND WARNINGS

Sotret must not be used by female patients who are or may become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking iSotretinoin capsules in any amount, even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. There are no accurate means of determining whether an exposed fetus has been affected.

Birth defects which have been documented following iSotretinoin exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Cases of IQ scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion, and premature births have been reported.

Documented external abnormalities include: skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (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 the abnormalities previously noted.

If pregnancy does occur during treatment of a female patient who is taking iSotretinoin capsules, iSotretinoin capsules must be discontinued immediately and she should be referred to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling.

Special Prescribing Requirements

Because of iSotretinoin’s teratogenicity and to minimize fetal exposure, Sotret is approved for marketing only under a special restricted distribution program approved by the Food and Drug Administration. This program is called iPLEDGE™. Sotret must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Sotret capsules must only be dispensed by a pharmacy registered and activated with iPLEDGE, and must only be dispensed to patients who are registered and meet all the requirements of iPLEDGE (see PRECAUTIONS).

Table 1 Monthly Required iPLEDGE Interactions

Female Patients of Childbearing Potential Male Patients, And Female Patients Not of Childbearing Potential
PRESCRIBER
Confirms patient counseling X X
Enters the 2 contraception methods chosen by the patient X
Enters pregnancy test results X
PATIENT
Answers educational questions before every prescription X
Enters 2 forms of contraception X
PHARMACIST
Calls system to get an authorization X X

Adverse Reactions

Clinical Trials and Postmarketing Surveillance

The adverse reactions listed below reflect the experience from investigational studies of iSotretinoin capsules, and the postmarketing experience. The relationship of some of these events to iSotretinoin capsules therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving iSotretinoin capsules are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, e.g., 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, esophagitis/esophageal ulceration, ileitis, nausea, other nonspecific gastrointestinal symptoms

Hematologic

allergic reactions (see PRECAUTIONS: Hypersensitivity), anemia, thrombocytopenia, neutropenia, rare reports of agranulocytosis (see PRECAUTIONS: Information for Patients). See PRECAUTIONS: Laboratory Tests for other hematological parameters.

Musculoskeletal

skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, decreases in bone mineral density (see WARNINGS: Skeletal), musculoskeletal symptoms (sometimes severe) including back pain, myalgia, and arthralgia (see PRECAUTIONS: Information for Patients), transient pain in the chest (see PRECAUTIONS: Information for Patients), arthritis, tendonitis, other types of bone 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

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 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 granulomatosis; see PRECAUTIONS: Hypersensitivity), abnormal wound healing (delayed healing or exuberant granulation tissue with crusting; see PRECAUTIONS: Information for Patients)

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 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 Patients), elevated sedimentation rates, elevated platelet counts, thrombocytopenia

White cells in the urine, proteinuria, microscopic or gross hematuria

Sotret Dosage and Administration

Sotret should be administered with a meal (see PRECAUTIONS: Information for Patients).

The recommended dosage range for Sotret is 0.5 to 1.0 mg/kg/day given in two divided doses with food 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. 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. 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 Sotret with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions.

The safety of once daily dosing with Sotret has not been established. Once daily dosing is not recommended.

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. Long-term use of Sotret, even in low doses, has not been studied, and is not recommended. It is important that Sotret be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Sotret 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 PRECAUTIONS).

Table 3 Sotret Dosing by Body Weight (Based on Administration With Food)

Body Weight Total mg/day

*See DOSAGE AND ADMINISTRATION: the recommended dosage range is 0.5 to 1.0 mg/kg/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

How is Sotret Supplied

Soft gelatin capsules, 10 mg (light pink), imprinted “5R”.

Boxes of 30 containing 3 Prescription Packs of 10 capsules (NDC 10631-584-31)

Boxes of 100 containing 10 Prescription Packs of 10 capsules (NDC 10631-584-77)

Soft gelatin capsules, 20 mg (maroon), imprinted “6R”.

Boxes of 30 containing 3 Prescription Packs of 10 capsules (NDC 10631-585-31)

Boxes of 100 containing 10 Prescription Packs of 10 capsules (NDC 10631-585-77)

Soft gelatin capsules, 30 mg (golden yellow), imprinted “8R”.

Boxes of 30 containing 3 Prescription Packs of 10 capsules (NDC 10631-447-31)

Boxes of 100 containing 10 Prescription Packs of 10 capsules (NDC 10631-447-77)

Soft gelatin capsules, 40 mg (yellow), imprinted “7R”.

Boxes of 30 containing 3 Prescription Packs of 10 capsules (NDC 10631-586-31)

Boxes of 100 containing 10 Prescription Packs of 10 capsules (NDC 10631-586-77)

Store at 20 - 25° C (68 - 77° F). (See USP Controlled Room Temperature). Protect from light.

For the Consumer

Applies to isotretinoin: oral capsule, oral capsule liquid filled

Along with its needed effects, isotretinoin (the active ingredient contained in Sotret) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking isotretinoin:

More common
  • Bone or joint pain
  • burning, redness, itching, or other signs of eye inflammation
  • difficulty with moving
  • nosebleeds
  • scaling, redness, burning, pain, or other signs of inflammation of the lips
  • skin infection or rash
Rare
  • Abdominal or stomach pain (severe)
  • attempts at suicide or thoughts of suicide (usually stops after medicine is stopped)
  • back pain
  • bleeding or inflammation of the gums
  • blurred vision or other changes in vision
  • changes in behavior
  • decreased vision after sunset or before sunrise (sudden or may continue after medicine is stopped)
  • diarrhea (severe)
  • headache (severe or continuing)
  • mental depression
  • nausea and vomiting
  • pain or tenderness of the eyes
  • pain, tenderness, or stiffness in the muscles (long-term treatment)
  • rectal bleeding
  • yellow eyes or skin
Incidence not known
  • Black, tarry stools
  • bloating
  • bloody cough
  • bloody or cloudy urine
  • bone pain, tenderness, or aching
  • burning or stinging of the skin
  • chest pain
  • confusion
  • constipation
  • convulsions
  • cough or hoarseness
  • dark-colored urine
  • decrease in height
  • difficulty breathing
  • difficulty speaking
  • difficulty swallowing
  • discharge from the eyes
  • dizziness
  • double vision
  • ear pain
  • excessive tearing
  • fainting
  • fast, irregular, pounding, or racing heartbeat or pulse
  • fever with or without chills
  • fractures and/or delayed healing
  • heartburn
  • high blood pressure
  • hives or skin rash
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • indigestion
  • inflamed tissue from infection
  • irregular yellow patch or lump on the skin
  • irritation
  • joint pain, redness, stiffness, or swelling
  • lack or slowing of normal growth in children
  • loosening of the fingernails
  • loss of appetite
  • loss of bladder control
  • loss or change in hearing
  • muscle cramps, spasms, or weakness
  • pain in the ribs, arms, or legs
  • pain or burning in the throat
  • pain or tenderness around the eyes and cheekbones
  • painful cold sores or blisters on the lips, nose, eyes, or genitals
  • painful or difficult urination
  • pains in the chest, groin, or legs, especially calves of the legs
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • pale skin
  • pinpoint red spots on the skin
  • redness or soreness around the fingernails
  • redness, soreness, or itching skin
  • sensitivity of the eyes to sunlight
  • sneezing
  • sores, ulcers, or white spots on the lips or tongue or inside the mouth
  • stuffy or runny nose
  • sudden loss of consciousness
  • sudden loss of coordination
  • sudden onset of severe acne on the chest and trunk
  • sudden onset of slurred speech
  • swelling of the eyelids, face, lips, hands, lower legs, or feet
  • swollen, painful or tender lymph glands in the neck, armpit, or groin
  • tightness in the chest
  • unusual bleeding or bruising
  • unusual weight gain or loss
  • use of extreme physical or emotional force
  • watery or bloody diarrhea

Some side effects of isotretinoin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Crusting of the skin
  • difficulty in wearing contact lenses (may continue after medicine is stopped)
  • dryness of the eyes (may continue after treatment is stopped)
  • dryness of the mouth or nose
  • dryness or itching of the skin
  • headache (mild)
  • increased sensitivity of the skin to sunlight
  • peeling of the skin on palms of the hands or soles of the feet
  • stomach upset
  • thinning of the hair (may continue after treatment is stopped)
Incidence not known
  • Abnormal menstruation
  • burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feeling
  • changes in fingernails or toenails
  • continuing ringing or buzzing, or other unexplained noise in the ears
  • dandruff
  • darkening of the skin
  • flushing
  • hair abnormalities
  • hair loss
  • increased hair growth, especially on the face
  • lightening of normal skin color
  • lightening of treated areas of dark skin
  • nervousness
  • oily skin
  • redness of the face
  • severe sunburn
  • skin rash, encrusted, scaly and oozing
  • stomach burning
  • sweating
  • trouble sleeping
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
  • unusually warm skin of the face
  • voice changes

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