PACKAGE LEAFLET: INFORMATION FOR THE USER OF ISOTRETINOIN
isotretinoin 10 mg
isotretinoin 20 mg
WARNING: THIS MEDICINE MAY CAUSE SERIOUS HARM TO AN UNBORN CHILD IF USED DURING PREGNANCY.
Women should use effective contraception.
Do not use if you are pregnant or think you may be pregnant.
1. WHAT IS ISOTRETINOIN AND WHAT IS IT USED FOR?
• Isotretinoin is related to vitamin A.
• It belongs to a group of medicines called retinoids (used to treat acne). Isotretinoin is used to treat severe forms of acne.
• This is acne that can cause permanent scarring in adults and adolescents from the age of 12 years only after puberty.
• These types of acne are also called “nodular” or “conglobata” acne.
Isotretinoin is used when your acne has not improved despite other treatments. These include antibiotics and skin treatments. Your treatment should be supervised by a dermatologist. This is a doctor who specialises in treating skin problems.
2. WHEN YOU SHOULD NOT USE THIS MEDICINE When you should not use this medicine
• If you are allergic to peanut or soya or any of the other ingredients of this medicine (listed in section 6). This medicine contains soya oil, as well as isotretinoin. These ingredients are listed in section 6.
• If you are pregnant or breast-feeding.
• If there is a chance that you could become pregnant, you must follow the precautions described in the 'Pregnancy prevention programme'.
• If you have liver problems.
• If you have very high levels of fats in your blood (such as high cholesterol or triglycerides).
• If you have very high levels of vitamin A in the body (hypervitaminosis A).
• If you are being treated with tetracyclines (a type of antibiotic) at the same time (see 'Other medicines and Isotretinoin').
If any of the above applies to you, go back to your doctor before taking this medicine.
Warnings and precautions
• If you have persistent pain in your lower back or buttocks during treatment with Isotretinoin, tell your doctor. These symptoms may be signs of sacroiliitis, a type of inflammatory back pain. Your doctor may stop your Isotretinoin treatment and refer you to a specialist to treat your inflammatory back pain. Further investigation may be necessary, including imaging methods such as MRI.
Pregnancy Prevention Program
Women who are pregnant must not take this medicine. This medicine can seriously harm your unborn child (the medicine is teratogenic). It can cause serious abnormalities of the brain, face, ears, eyes, heart and certain glands (thymus and parathyroid) of your unborn child. There is also an increased risk of miscarriage. This can even occur if this medicine is used for a short time during pregnancy.
• You must not take this medicine if you are pregnant or think you may be pregnant.
• You must not take this medicine if you are breast-feeding. This medicine is likely to pass into breast milk and may harm your baby.
• You must not take this medicine if you become pregnant during treatment.
• After stopping treatment, you must not become pregnant for 1 month because this medicine may still be present in your body.
Women who could become pregnant are only prescribed isotretinoin under strict conditions due to the risk of birth defects (harmful effects on the unborn child).
These are the conditions:
• Your doctor must explain to you the risk of harm to your unborn child. You must understand why you must not become pregnant and what you must do to avoid becoming pregnant.
• You must discuss possible methods of preventing pregnancy (contraceptives) with your doctor. Your doctor can give you information on what you must do to prevent pregnancy. Your doctor may refer you to a specialist for advice about contraception.
• Before starting treatment, your doctor will ask you to take a pregnancy test. The test must show that you are not pregnant at the time you start treatment with this medicine. Women must use effective contraception (contraceptives) before, during and after treatment with isotretinoin.
• You must agree to use at least one reliable method of contraception (for example, an intrauterine device (IUD) or contraceptive implant) or two effective methods of contraception that work in different ways (for example, a hormonal contraceptive pill (the pill) and a condom). Discuss with your doctor which method is suitable for you.
• You must use a contraceptive for 1 month before starting treatment with this medicine, during treatment and for 1 month after stopping treatment.
• You must use a contraceptive method even if you do not have a period and are not currently sexually active (unless your doctor decides this is not necessary). Women must agree to pregnancy tests before, during and after treatment with isotretinoin.
• You must agree to regular check-ups with your doctor, preferably every month.
• You must agree to regular pregnancy tests, preferably every month. Because this medicine can remain in your body for 1 month after stopping treatment with isotretinoin, it is necessary to perform a pregnancy test then as well (unless your doctor decides this is not necessary).
• You must agree to additional pregnancy tests when requested by your doctor.
• You must not become pregnant during treatment or for 1 month after treatment, as this medicine may still be present in your body.
• Your doctor will discuss all these points with you using a pregnancy check-up form. You (or your parent/guardian) will have to sign this form. This form confirms that you have received the information about the risks and that you will adhere to the conditions.
If you become pregnant during treatment with isotretinoin, you must immediately stop taking this medication and contact your doctor. Your doctor can refer you to a specialist for further advice. Termination of the pregnancy (abortion) is usually recommended due to the high risk of birth defects. If you become pregnant within 1 month of stopping treatment with this medication, you must contact your doctor. Your doctor can refer you to a specialist for further advice. Your doctor has written information about pregnancy prevention for users of this medication. You should obtain this information from your doctor.
Each prescription can be dispensed to women of childbearing potential for up to 30 days of treatment. A new prescription is required to extend treatment. Each prescription is valid for only 7 days.
Advice for men
Very low amounts of isotretinoin are found in the semen of men taking isotretinoin, but this is too low to harm your partner's unborn child. You must never share your medication with others.
Additional precautions
• You must never share this medicine with others. Unused capsules should be returned to your pharmacist at the end of treatment.
• You must not donate blood during treatment with this medicine and for 1 month after stopping isotretinoin, because an unborn baby may be harmed if a pregnant patient receives your blood.
Other warnings and precautions
• Serious skin reactions (for example, erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN)) have been reported with this medicine. The rash may progress to widespread blistering or peeling of the skin. You should also look out for ulcers of the mouth, throat, nose or genitals, and conjunctivitis (red and swollen eyes).
• Rarely, this medicine may cause allergic reactions, some of which may affect the skin in the form of eczema, hives, bruising or red patches on the arms and legs. If you have an allergic reaction, stop taking this medicine, contact your doctor as soon as possible and tell them that you are taking this medicine.
• Reduce strenuous exercise and physical activity. This medicine can cause muscle and joint pain, especially in children and teenagers doing vigorous physical activity.
• Isotretinoin has been associated with inflammation of the gut. If you have severe bloody diarrhoea and have never had gut problems before, your doctor may want to stop your treatment with this medicine.
• Isotretinoin can cause dry eyes, intolerance to contact lenses, and vision problems, including reduced night vision. Cases of dry eyes that have not improved after stopping treatment have been reported. Tell your doctor if you experience any of these symptoms. Your doctor may ask you to use a lubricating eye ointment or artificial tears. If you are no longer able to tolerate your contact lenses, you may be advised to wear glasses during treatment. Your doctor may refer you to a specialist if you have vision problems and may ask you to stop treatment with this medicine.
• Benign intracranial hypertension has been reported with isotretinoin use and in some cases when this medicine was used at the same time as tetracyclines (a type of antibiotic). Stop taking this medicine and contact your doctor as soon as possible if you experience symptoms such as headache, nausea, vomiting and vision problems. Your doctor may refer you to a specialist to check for fluid retention in the eye (papilloedema).
• Isotretinoin can increase the levels of liver enzymes in your blood.
• Isotretinoin often increases the level of fats in the blood, such as cholesterol or triglycerides. During treatment, it is best to avoid alcoholic drinks or drink less than you usually do. Tell your doctor if you have ever had high blood fats or diabetes (high blood sugar), are overweight, or are dependent on alcohol. Your blood may be checked. If the level of fats in your blood is too high, your doctor may reduce your dose or stop treatment with this medicine.
• Tell your doctor if you have kidney problems. Your doctor may start you on a lower dose of this medicine and then increase it to the maximum tolerated dose.
• Tell your doctor if you have fructose intolerance. Your doctor will not prescribe this medicine if you have an intolerance to fructose or sorbitol.
• Isotretinoin can increase blood sugar levels. In rare cases, patients may develop diabetes. Your doctor may monitor your blood sugar levels during treatment, especially if you already have diabetes, are overweight, or are dependent on alcohol.
• Your skin will probably become dry. Use a moisturizing ointment or cream and a lip balm during treatment. To prevent skin irritation, avoid scrubs and anti-acne products.
• Avoid too much sun and do not use a sunbed or tanning bed. Your skin may become more sensitive to sunlight. Before going out in the sun, apply a sunscreen with a high protection factor (SPF 50 or higher).
• Do not have cosmetic skin treatments. This medicine can make your skin more fragile. Do not have hair removal with wax, dermabrasion, or laser treatments to remove calluses or scars during treatment and for at least 6 months afterwards. This could cause scarring, skin irritation, or rarely, changes in skin color.
Use in adolescents over 12 years of age:
Do not give this medicine to children under 12 years of age. This is because it is not known whether it is safe and effective in this age group. Only give it to adolescents over 12 years of age if they have completed all changes of puberty.
Are you taking any other medicines?
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
• Do not take vitamin A supplements or tetracyclines (a type of antibiotic).
• Do not use other acne treatments that will dry out your skin or make it flake while using this medicine. It is fine to use moisturising ointments or creams and emollients (skin creams or preparations that prevent moisture loss and have a softening effect on the skin).
Pregnancy, breast-feeding and fertility
If you are pregnant, think you may be pregnant, are planning to have a baby, or are breast-feeding, talk to your doctor before taking this medicine.
Driving and using machines
You may experience problems with your vision at night during treatment. This can happen suddenly. In rare cases, this problem has continued after stopping treatment. Drowsiness and dizziness have been reported very rarely. If this happens to you, do not drive, cycle or operate machinery.
Isotretinoin contains:
• Soya-bean oil. Do not take this medicine if you are allergic to peanut or soya.
• Sorbitol. Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance, a rare hereditary condition, you (or your child) should not be given this medicine. Patients with hereditary fructose intolerance cannot break down fructose. This can cause serious side effects.
3. HOW TO USE THIS MEDICINE: Always use this medicine exactly as your doctor or pharmacist has told you. If you are unsure about the correct use, contact your doctor or pharmacist. The capsules should not be chewed; they should be swallowed whole. The recommended starting dose is 0.5 mg per kilogram (kg) of body weight per day (0.5 mg/kg/day). So, if you weigh 60 kilograms, you will usually start with 30 mg per day. In recent years, however, a lower dose (20 mg) is often started because this is often sufficient and causes fewer side effects.
Take the capsules once or twice a day. Take the capsules with or after a meal. Swallow the capsules whole with a drink or a mouthful of food. After a few weeks, your doctor may adjust your dose. This depends on how you tolerate the medicine.
If you think your dose of this medicine is too high or too low, talk to your doctor or pharmacist. If you have severe kidney problems, your starting dose will usually be lower (such as 10 mg/day) and then increased to the highest dose your body can tolerate. If your body cannot tolerate the recommended dose, you may be prescribed a lower dose: this may mean that you need treatment for longer and your acne may come back more quickly.
Treatment usually lasts 16 to 24 weeks. Most patients only need one course of treatment. Your acne may continue to improve for up to 8 weeks after treatment. You are unlikely to start another course of treatment before that. In some people, acne gets worse during the first few weeks of treatment. Acne usually improves as treatment continues. If
you use more of this medicine than you should
If you have taken too many capsules, or if someone else accidentally takes your medicine, contact your doctor, pharmacist, or nearest hospital immediately. If
you forget to take this medicine
If you miss a dose, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take your medicine as before. Do not take a double dose (two doses close together).
4. POSSIBLE SIDE EFFECTS Like all medicines, this medicine can cause side effects, although not everyone gets them. These side effects often lessen over time or disappear when treatment is stopped. Your doctor can help you manage these side effects.
Side effects that require immediate medical attention:
Skin disorders
Not known how often (frequency cannot be estimated from the available data)
• Serious skin reactions (for example erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), which are potentially life-threatening and require immediate medical attention. These appear initially as circular patches, often with central blisters, usually on the arms and hands or legs and feet. More severe rashes may include blisters on the chest and back. Other symptoms may occur such as an eye infection (conjunctivitis) or ulcers of the mouth, throat or nose. Severe rashes may progress to extensive peeling of the skin which may be life-threatening. These severe rashes are often preceded by headache, fever and body aches (flu-like symptoms). If you develop a severe rash or if these skin symptoms occur, stop taking this medicine and contact your doctor immediately.
Allergic reactions
Rare (affecting less than 1 in 1,000 people)
• Serious (anaphylactic) reactions such as difficulty breathing or swallowing due to sudden swelling of the throat, face, lips and mouth. Also sudden swelling of the hands, feet and ankles. Very rare (affecting less than 1 in 10,000 people).
• Sudden tightness in the chest, shortness of breath and wheezing, especially if you have asthma. If you have a severe reaction, get emergency medical help straight away. If you have an allergic reaction, stop taking this medicine and contact your doctor.
Bones and muscles
Not known how often (frequency cannot be estimated from the available data).
• Muscle weakness, which can be life-threatening, may be accompanied by problems moving your arms or legs, painful, swollen, bruised areas on the body, dark-coloured urine, reduced or no urine, confusion or dehydration. These are signs of rhabdomyolysis, a breakdown of muscle tissue that can lead to kidney failure. This may happen if you do intense physical activity during treatment with this medicine.
• Sacroiliitis, a type of inflammatory back pain that may cause pain in your buttocks or lower back.
Liver and kidney disorders
Very rare (may affect up to 1 in 10,000 people)
• Yellowing of the skin or eyes, feeling tired. These may be signs of hepatitis. Stop taking this medicine immediately and contact your doctor.
• Difficulty in urinating, swollen and puffy eyelids, feeling overly tired. These may be signs of kidney problems. Stop taking this medicine immediately and contact your doctor.
Nervous system disorders
Very rare (may affect up to 1 in 10,000 people)
• Persistent headache accompanied by nausea, vomiting and changes in vision including blurred vision. These may be signs of benign intracranial hypertension, particularly if this medicine is used in combination with antibiotics called tetracyclines. Stop taking this medicine immediately and contact your doctor.
Gastrointestinal disorders
Very rare (may affect up to 1 in 10,000 people)
• Severe pain in the abdomen with or without severe bloody diarrhoea, nausea and vomiting. These may be signs of serious gut conditions. Stop taking this medicine immediately and contact your doctor.
Eye disorders
Very rare (may affect up to 1 in 10,000 people)
• Blurred vision. If you get blurred vision, stop taking this medicine immediately and contact your doctor. If your vision is affected in any other way, tell a doctor as soon as possible.
Other side effects
Very common (may affect more than 1 in 10 people):
• Dryness of the skin, especially of the lips and face; inflamed skin, chapped and inflamed lips, rash, mild itching and mild peeling. Using a moisturiser from the start of treatment can reduce the risk of this happening.
• The skin may become more fragile and redder than usual, especially on the face.
• Back pain, muscle pain, joint pain, especially in children and teenagers. To avoid making any bone or muscle disorders worse, you should avoid strenuous physical activity during treatment with this medicine.
• Inflammation of the eye (conjunctivitis) and the area around the eyelids; eyes feel dry and irritated. Ask your pharmacist for suitable eye drops. If you get dry eyes and wear contact lenses, you may need to wear glasses instead of contact lenses.
• Increased liver enzymes seen in blood tests.
• Changes in the levels of fats in the blood (including HDL or triglycerides).
• Bruising, tendency to bleed - if the number of blood clotting cells falls.
• Anaemia - weakness, dizziness, pale skin - if the number of red blood cells falls
Common (may affect up to 1 in 10 people):
• Headache.
• Higher cholesterol levels in the blood.
• Protein or blood in the urine.
• More likely to get infections, if the white blood cells are affected.
• The inside of the nose becomes dry and crusted, which can cause minor nose bleeds.
• Sore or inflamed throat and nose.
• Allergic reactions such as skin rash and itching. If you have an allergic reaction, stop taking this medicine and contact your doctor.
Rare (may affect up to 1 in 1,000 people):
• Hair loss (alopecia). This is usually temporary. Your hair should grow back after stopping treatment.
Very rare (may affect up to 1 in 10,000 people):
• Your night vision may become worse; colour blindness and colour vision may get worse.
• Sensitivity to light may be increased; you may need to use sunglasses to protect your eyes from bright sunlight.
• Other vision problems such as blurred vision, distorted images, clouding of the cornea (corneal opacity, cataracts).
• Excessive thirst; frequent need to urinate; blood tests show an increase in your blood sugar. These may all be signs of diabetes.
• Acne may get worse in the first few weeks, but symptoms should improve with time.
• Inflamed skin, swollen and darker than usual, especially on the face.
• Excessive sweating or itching.
• Arthritis; bone disorders (slowed growth, extra growth and changes in bone density); growing bones may stop growing.
• Calcium deposits in soft tissues.
• Painful tendons.
• High levels of muscle breakdown products in your blood if you exercise vigorously.
• Increased sensitivity to light.
• Bacterial infections of the nail, changes to the nails.
• Swelling, discharge, pus.
• Thickened scar tissue after surgery.
• Increased body hair.
• Convulsions (fits), drowsiness, dizziness.
• Lymph nodes may swell.
• Dry throat, hoarseness.
• Hearing problems.
• Generally feeling unwell.
• High uric acid levels in the blood.
• Bacterial infections.
• Inflammation of the blood vessels (sometimes with bruising, red spots)
Not known how often (the frequency cannot be estimated from the available data):
• Dark or cola-coloured urine.
• Inflammation of the urethra.
• Problems getting or maintaining an erection.
• Decreased libido.
• Breast enlargement in men, with or without tenderness.
• Vaginal dryness
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This also applies to any possible side effects not listed in this leaflet. You can also report side effects directly via the Netherlands Pharmacovigilance Centre Lareb, website: www.lareb.nl. By reporting side effects you can help provide more information on the safety of this medicine.
5. HOW TO STORE THIS MEDICINE: Keep out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton and blister pack after "EXP:". These dates indicate a month and a year. The expiry date refers to the last day of that month. Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering. This medicine does not require any special temperature storage conditions. Store in the original package. Keep the blister pack in the outer carton in order to protect from light. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. Return any unused capsules to your pharmacist. Only keep them if your doctor tells you to.
6. CONTENTS OF THE PACK AND OTHER INFORMATION What this medicine contains:
• The active substance in this medicine is isotretinoin.
• The other ingredients are all-rac-alpha-tocopheryl acetate, hydrogenated vegetable oil (soybean type II), hydrogenated soybean oil, yellow beeswax, refined soybean oil, gelatin, glycerol, partially dehydrated sorbitol liquid, titanium dioxide (E171), purified water, 10 mg capsules also contain patent blue V (E131) and ponceau red 4R (E124), 20 mg capsules also contain sunset yellow FCF (E110).
What Isotretinoin looks like and contents of the pack
Isotretinoin is contained in soft capsules containing 10 mg or 20 mg isotretinoin. 10 mg: Size 3, violet, oval soft capsules. The length of the capsule is approximately 11.1 mm and the width is approximately 6.8 mm. 20 mg: Size 6, off-white to cream-colored, oval soft capsules. The capsule is approximately 13.8 mm long and 8.1 mm wide. Blister packaging with orange PVC/TE/PVDC/aluminum foil. Pack sizes for 10 mg and 20 mg capsules: 30, 50, 60, and 100 capsules. |
