ISOTRETINOIN (Systemic)

Some commonly used brand names are:

In the U.S.?

• Accutane

In Canada?

• Accutane Roche

Category

• Antiacne agent, systemic
• Antirosacea agent, systemic
• Keratinization stabilizer

Description

Isotretinoin (eye-soe-TRET-i-noyn) is used to treat severe, disfiguring nodular acne. Itshould be used only after other acne medicines have been tried and have failedto help the acne. Isotretinoin may also be used to treat other skin diseasesas determined by your doctor.

Isotretinoin must not be used to treat women who areable to bear children unless other forms of treatment have been tried firstand have failed. Isotretinoin must not be taken during pregnancy because itcauses birth defects in humans. If you are able to bear children, it is veryimportant that you read, understand, and follow the pregnancy warnings forisotretinoin.

This medicine is available only with your doctor's prescription and shouldbe prescribed only by a doctor who has special knowledge of the diagnosisand treatment of severe, uncontrollable cystic acne.

Isotretinoin is available in the following dosage form:

Oral
• Capsules (U.S. and Canada)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For isotretinoin, thefollowing should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to isotretinoin, acitretin, etretinate, tretinoin, or vitaminA preparations. Also tell your health care professional if you are allergicto any other substances, such as foods, preservatives (such as parabens),or dyes.

Pregnancy?Isotretinoin must not be takenduring pregnancy because it causes birth defects in humans. In addition, isotretinoinmust not be taken if there is a chance that you may become pregnant duringtreatment or within 1 month following treatment.

Breast-feeding?It is not known whether isotretinoin passes intobreast milk. However, isotretinoin should not be used during breast-feedingbecause it may cause unwanted effects in nursing babies.

Children?Children may be especially sensitive to the effectsof isotretinoin. This may increase the chance of side effects during treatment.Children may have the side effects of back, joint, or muscle pain more oftenthan adults.

This medicine should be used with caution in teenagers, especially thosewith bone problems or diseases.

Older adults?Many medicines have not been studied specificallyin older people. Therefore, it may not be known whether they work exactlythe same way they do in younger adults or if they cause different side effectsor problems in older people. There is no specific information comparing useof isotretinoin in the elderly with use in other age groups. However, olderpeople may have a greater risk of problems and adverse effects when takingisotretinoin.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are usingisotretinoin, it is especially important that your health care professionalknow if you are using any of the following:

• Acitretin (e.g., Soriatane) or
• Tretinoin, oral (e.g., Vesanoid)?Use of isotretinoin with thesemedicines may result in an increase in side effects

• Hormonal contraceptives (birth control pills, topical [e.g., OrthoEvra], implantable [e.g., Nuvaring], injectable [e.g., Depo-Provera])?Itis possible that these medicines are not effective forms of birth controlwhen used with isotretinoin. Healthcare professionals have been unable torule this out. Because any birth control method can fail, it is very importantthat two effective forms of birth control are used. It is also important thatyou read the warnings about possible birth control failure included in yourpatient education kit.

• Oral contraceptives, progestin-only or ?mini pills? (birthcontrol pills) (e.g., Nor-QD, Micronor, Ovrette)?This medication isnot an effective form of birth control when used with isotretinoin.

• Tetracyclines, oral (medicine for infection)?Use of isotretinoinwith these medicines may increase the chance of a side effect called pseudotumorcerebri, which is a swelling and pressure on the brain

Other medical problems?The presence of other medicalproblems may affect the use of isotretinoin. Make sure you tell your doctorif you have any other medical problems, especially:

• Alcoholism or excess use of alcohol (or history of) or
• Diabetes mellitus (sugar diabetes) (or a family history of) or
• Family history of high triglyceride (a fat-like substance) levelsin the blood or
• Severe weight problems?Use of isotretinoin may increase bloodlevels of triglyceride (a fat-like substance), which may increase the chanceof heart or blood vessel problems in patients who have a family history ofhigh triglycerides, are greatly overweight, are diabetic, or use a lot ofalcohol. For persons with diabetes mellitus, use of isotretinoin also maychange blood sugar levels

• Anorexia (eating disorder)
• Osteoporosis (brittle bones), childhood or family history of
• Osteomalacia (softening of the bones)
• Other bone disorders or diseases?Isotretinoin should be usedwith caution. It is not known whether this medicine effects bone loss.

• Kidney disease or
• Lipids in blood, sudden and large increase or
• Liver disease or
• Vitamin A overdose (too much vitamin A in your body)?Isotretinoinshould not be used in patients with these medical problems.

• Mental disorders such as mental depression or psychosis?Isotretinoinmay make these problems worse.

Proper Use of This Medicine

Isotretinoin comes with patient information. It is very important that youread and understand this information. Be sure to ask your doctor about anythingyou do not understand.

Women of reproductive age are required to sign up fora pregnancy risk program called iPLEDGE in order to receive their isotretinoinprescription each month. You can sign up on the internet (www.ipledge.com)or by telephone (1-866-495-0654). Be sure to ask your doctor if you have anyquestions about this program. It is very important that you understand andfollow all of its requirements.

Isotretinoin must not be taken by women of reproductiveage unless two effective forms of contraception (birth control) have beenused for at least 1 month before the beginning of treatment. Contraceptionmust be continued during the period of treatment, which is up to 20 weeks,and for 1 month after isotretinoin is stopped. Be sure you have discussedthis information with your doctor.

If you are a woman who is able to have children, you must have a pregnancyblood test within 1 week before beginning treatment with isotretinoin to makesure you are not pregnant. Treatment with isotretinoin will then be startedwithin the week, on the second or third day of your next normal menstrualperiod. In addition, you must have a pregnancy blood test each month whileyou are taking this medicine and one month after treatment is completed.

Take isotretinoin with food and a full glass of liquid,like water. Taking with food is important for getting the right amountof medicine out of your stomach. Taking with a full glass of liquid will reducechest or stomach discomfort that may occur from isotretinoin.

It is very important that you take isotretinoin onlyas directed. Do not take more of it, do not take it more often, anddo not take it for a longer time than your doctor ordered. To do so may increasethe chance of side effects.

Importance of not sharing medication with anyone elsebecause of the risk of birth defects and other serious side effects.

Dosing?The dose of isotretinoin will be differentfor different patients. Follow your doctor's orders orthe directions on the label. The following information includes onlythe average doses of isotretinoin. If your dose is different,do not change it unless your doctor tells you to do so.

The number of capsules that you take depends on the strength of the medicine.Also, the number of doses you take each day, the timeallowed between doses, and the length of time you take the medicine dependon the medical problem for which you are taking isotretinoin.

• For oral dosage form (capsules):
  • For acne:
    • Adults and teenagers?Dose is based on body weight and mustbe determined by your doctor. The usual dose is 0.5 to 1 milligram (mg) perkilogram (kg) (0.23 to 0.45 mg per pound) of body weight a day. It is recommendedthat the dose per day be divided and not taken all at one time. For adultpatients with severe acne, dosage adjustments may be needed and must be determinedby your doctor.
    • Children?Use is usually not recommended.

Missed dose?If you miss a dose of this medicine, take it assoon as possible. However, if it is almost time for your next dose, skip themissed dose and go back to your regular dosing schedule. Do not double doses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store in the bathroom, near the kitchen sink, or in otherdamp places. Heat or moisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

Your doctor should check your progress at regular visitsto make sure this medicine does not cause unwanted effects.

Isotretinoin causes birth defects in humans if takenduring pregnancy. Therefore, if you suspect that you may have become pregnant,stop taking this medicine immediately and check with your doctor.

Importance of checking with your doctor before takingany medications including vitamins, herbal products, or over-the-counter (OTC)medicines. Some of these medicines or nutritional supplements (e.g.,St. John's wort) may make your birth control pills not work.

During the first 3 weeks you are taking isotretinoin, your skin may becomeirritated. Also, your acne may seem to get worse before it gets better. Check with your doctor if your skin condition does not improvewithin 1 to 2 months after starting this medicine or at any time your skinirritation becomes severe. Full improvement continues after you stoptaking isotretinoin and may take up to 6 months. Your health care professionalcan help you choose the right skin products to reduce skin dryness and irritation.

Do not donate blood to a blood bank while you are takingisotretinoin or for 30 days after you stop taking it. This is to preventthe possibility of a pregnant patient receiving the blood containing the medicine.

In some patients, isotretinoin may cause a decrease in night vision. Thisdecrease may occur suddenly. If it does occur, do notdrive, use machines, or do anything else that could be dangerous if you arenot able to see well. Also, check with your doctor.

Isotretinoin may cause dryness of the eyes. Therefore, if you wear contactlenses, your eyes may be more sensitive to them during the time you are takingisotretinoin and for up to about 2 weeks after you stop taking it. To helprelieve dryness of the eyes, check with your doctor about using an eye-lubricatingsolution, such as artificial tears. If eye inflammation occurs, check withyour doctor.

Isotretinoin may cause dryness of the mouth and nose. For temporary reliefof mouth dryness, use sugarless candy or gum, melt bits of ice in your mouth,or use a saliva substitute. However, if dry mouth continues for more than2 weeks, check with your medical doctor or dentist. Continuing dryness ofthe mouth may increase the chance of dental disease, including tooth decay,gum disease, and fungus infections.

Avoid overexposing your skin to sunlight, wind, orcold weather. Your skin will be more prone to sunburn, dryness, orirritation, especially during the first 2 or 3 weeks of treatment. However,you should not stop taking this medicine unless the skin irritation becomestoo severe. Do not use a sunlamp.

To help isotretinoin work properly, regularly use sunscreen or sunblockinglotions with a sun protection factor (SPF) of at least 15. Also, wear protectiveclothing and hats.

Isotretinoin may cause mood or behavior problems, including having thoughtsabout hurting themselves; check with you doctor right away if unusual moodor behavior problems occur.

Isotretinoin may cause bone or muscle problems, including joint pain, musclepain or stiffness, or difficulty moving. Check with your doctor if these problemsare bothersome.

Do not take vitamin A or any vitamin supplement containingvitamin A while taking this medicine, unless otherwise directed byyour doctor. To do so may increase the chance of side effects.

Importance of not removing hair by wax epilation while taking isotretinoinand for 6 months after stopping isotretinoin. Isotretinoin can increase yourchance of scarring from wax epilation.

Importance of not having any cosmetic procedures to smooth your skin (e.g.,dermabrasion, laser) while taking isotretinoin and for 6 months after stoppingisotretinoin. Isotretinoin can increase your chance of scarring from thesecosmetic procedures.

For diabetic patients:

• This medicine may affect blood sugar levels. If you notice a changein the results of your blood or urine sugar tests or if you have any questions,check with your doctor.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

Check with your doctor as soon as possible if any of the following sideeffects occur:

More common

Bone or joint pain; burning, redness,itching, or other signs of eye inflammation; difficultyin moving; nosebleeds; scaling, redness, burning, pain, or other signs of inflammation of lips; skin infection or rash

Rare

Abdominal or stomach pain (severe); attempts at suicide or thoughts of suicide (usually stops after medicine isstopped); back pain; bleedingor inflammation of gums; blurred vision or otherchanges in vision; changes in behavior; decreased vision after sunset or before sunrise (sudden or maycontinue after medicine is stopped); diarrhea (severe); headache (severe or continuing); mental depression; nausea and vomiting; pain or tenderness of eyes; pain, tenderness,or stiffness in muscles (long-term treatment); rectalbleeding; yellow eyes or skin

Incidence not determined

Other side effects may occur that usually do not need medical attention.These side effects may go away during treatment as your body adjusts to themedicine. However, check with your doctor if any of the following side effectscontinue or are bothersome:

More common

Crusting of skin; difficulty in wearingcontact lenses (may continue after medicine is stopped); dryness of eyes (may continue after treatment is stopped); dryness of mouth or nose; dryness or itching of skin; headache (mild); increasedsensitivity of skin to sunlight; peeling of skinon palms of hands or soles of feet; stomach upset; thinning of hair (may continue after treatmentis stopped)

Incidence not determined

Other side effects not listedabove may also occur in some patients. If you notice any other effects, checkwith your doctor.

Additional Information

Once a medicine has been approvedfor marketing for a certain use, experience may show that it is also usefulfor other medical problems. Although these uses are not included in productlabeling, isotretinoin is used in certain patients with the following medicalconditions:

• Folliculitis, gram-negative (bacterial infection of skin on facebeginning near the nose)
• Hidradenitis suppurativa (sweat gland problem)
• Rosacea (red skin disorder of the face, usually of the nose and cheeks)
• Thickened or patchy skin disorders, such as keratosis follicularis,palmoplantar keratoderma, lamellar ichthyosis, or pityriasis rubra pilaris

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.