Isotretinoin

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isotretinoin

What is isotretinoin

Isotretinoin (13-cis-retinoic acid) is a synthetic retinoid derived from retinol (vitamin A) that is primarily used orally for the treatment of treat severe, disfiguring nodular acne (refractory nodulocystic acne vulgaris) and is approved in 1982 by the United States Food and Drug Administration (FDA) for this indication 1. Nodulocystic acne vulgaris causes many red, swollen lumps in the skin and leaves lasting scars. Isotretinoin should be used only after other acne medicines or antibiotics have been tried and have failed to help the acne. Isotretinoin may also be used to treat other skin diseases as determined by your doctor.

Isotretinoin is a kind of medicine called an oral retinoid. Retinoids are man-made forms of vitamin A used to treat certain skin conditions and blood cancers. Oral means it’s a medicine that’s taken by mouth. Accutane® was the original brand of isotretinoin. Accutane is no longer sold, but these brands are still used: Absorica®, Amnesteem®, Claravis®, Myorisan® and Sotret®.

Isotretinoin must not be used to treat women who are able to bear children unless other forms of treatment have been tried first and have failed. Isotretinoin must not be taken during pregnancy because it causes birth defects in humans. If you are able to bear children, it is very important that you read, understand, and follow the pregnancy warnings for isotretinoin.

Isotretinoin is available only under a registered distribution program called the iPLEDGE™ program (https://www.ipledgeprogram.com/iPledgeUI/home.u).

Isotretinoin can be prescribed under a special program called iPLEDGETM. Women MUST adhere to all requirements of the iPLEDGE program. Following are some of the requirements:

  • Women must be able to understand that severe birth defects can occur with use of isotretinoin.
  • Women must receive and be able to understand safety information about isotretinoin and the iPLEDGE requirements.
  • Women must sign an Informed Consent Form that contains warnings about the risks of using isotretinoin.
  • Women must not be pregnant or be breastfeeding.
  • Women must have two (2) negative pregnancy tests before starting isotretinoin.
  • Women must have a pregnancy test every month during treatment, and a negative test a month after treatment.
  • Women must use two (2) different forms of birth control at all times (unless woman agrees not to have sex) starting one (1) month before treatment continuing during treatment, and for one (1) month after treatment.
  • Women must fill their prescription within 7 days after the health care provider visit.
  • Women must agree to see their health care provider every month during treatment for a health check and to get a new prescription.

Taking isotretinoin or other retinoids during pregnancy can cause serious health problems for your baby. Here’s how to protect your baby:

  • If you’re pregnant or could get pregnant, don’t take isotretinoin or other retinoids.
  • If you take these medicines and could get pregnant, both you and your partner should use birth control.
  • If you take these medicines and are planning to get pregnant, talk to your health care provider about stopping the medicine before you get pregnant.
  • If you get pregnant and you’re taking a retinoid, tell your health care provider right away.

Non-FDA Approved indications

Isotretinoin has also been used for moderate acne, cutaneous T-cell lymphomas, neuroblastoma, and prevention of squamous cell carcinoma in high-risk patients. Isotretinoin has also been used in the treatment of rosacea, folliculitis, and pyoderma faciale 2.

Isotretinoin is a prescription medicine that is available in the following dosage forms:

  • Capsule
  • Capsule, Liquid Filled

Isotretinoin comes as a capsule to take by mouth. Isotretinoin should be taken with a full glass of water to avoid esophageal irritation. Do not chew, crush, or suck on the capsules. Isotretinoin is usually taken twice a day with meals for 4 to 5 months at a time. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take isotretinoin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Isotretinoin is commonly initiated at a dose of 0.5 mg/kg per day, and then gradually increased to a dose of 1.0 mg/kg per day according to patient tolerance. Typical therapy requires a 15- to 20-week course of daily isotretinoin administration to achieve complete prolonged remission of disease 2.

Your doctor will probably start you on an average dose of isotretinoin and increase or decrease your dose depending on how well you respond to the medication and the side effects you experience. Follow these directions carefully and ask your doctor or pharmacist if you are not sure how much isotretinoin you should take.

It may take several weeks or longer for you to feel the full benefit of isotretinoin. Your acne may get worse during the beginning of your treatment with isotretinoin. This is normal and does not mean that the medication is not working. Your acne may continue to improve even after you finish your treatment with isotretinoin.

IMPORTANT WARNING

For all patients:

Isotretinoin must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that isotretinoin will cause loss of the pregnancy, or will cause the baby to be born too early, to die shortly after birth, or to be born with birth defects (physical problems that are present at birth).

A program called iPLEDGE has been set up to make sure that pregnant women do not take isotretinoin and that women do not become pregnant while taking isotretinoin. All patients, including women who cannot become pregnant and men, can get isotretinoin only if they are registered with iPLEDGE, have a prescription from a doctor who is registered with iPLEDGE and fill the prescription at a pharmacy that is registered with iPLEDGE. Do not buy isotretinoin over the internet.

You will receive information about the risks of taking isotretinoin and must sign an informed consent sheet stating that you understand this information before you can receive the medication. You will need to see your doctor every month during your treatment to talk about your condition and the side effects you are experiencing. At each visit, your doctor may give you a prescription for up to a 30-day supply of medication with no refills. If you are a woman who can become pregnant, you will also need to have a pregnancy test in an approved lab each month and have your prescription filled and picked up within 7 days of your pregnancy test. If you are a man or if you are a woman who cannot become pregnant, you must have this prescription filled and picked up within 30 days of your doctor visit. Your pharmacist cannot dispense your medication if you come to pick it up after the allowed time period has passed.

Tell your doctor if you do not understand everything you were told about isotretinoin and the iPLEDGE program or if you do not think you will be able to keep appointments or fill your prescription on schedule every month.

Your doctor will give you an identification number and card when you start your treatment. You will need this number to fill your prescriptions and to get information from the iPLEDGE website and phone line. Keep the card in a safe place where it will not get lost. If you do lose your card, you can ask for a replacement through the website or phone line.

Do not donate blood while you are taking isotretinoin and for 1 month after your treatment.

Do not share isotretinoin with anyone else, even someone who has the same symptoms that you have.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with isotretinoin and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (https://www.fda.gov/Drugs/default.htm), the manufacturer’s website, or the iPLEDGE program website (https://www.ipledgeprogram.com/iPledgeUI/home.u) to obtain the Medication Guide.

Talk to your doctor about the risks of taking isotretinoin.

For female patients:

If you can become pregnant, you will need to meet certain requirements during your treatment with isotretinoin. You need to meet these requirements even if you have not started menstruating (having monthly periods) or have had a tubal ligation (‘tubes tied’; surgery to prevent pregnancy). You may be excused from meeting these requirements only if you have not menstruated for 12 months in a row and your doctor says you have passed menopause (change of life) or you have had surgery to remove your uterus and/or both ovaries. If none of these are true for you, then you must meet the requirements below.

You must use two acceptable forms of birth control for 1 month before you begin to take isotretinoin, during your treatment and for 1 month after your treatment. Your doctor will tell you which forms of birth control are acceptable and will give you written information about birth control. You can also have a free visit with a doctor or family planning expert to talk about birth control that is right for you. You must use these two forms of birth control at all times unless you can promise that you will not have any sexual contact with a male for 1 month before your treatment, during your treatment, and for 1 month after your treatment.

If you choose to take isotretinoin, it is your responsibility to avoid pregnancy for 1 month before, during, and for 1 month after your treatment. You must understand that any form of birth control can fail. Therefore, it is very important to decrease the risk of accidental pregnancy by using two forms of birth control at all times. Tell your doctor if you do not understand everything you were told about birth control or you do not think that you will be able to use two forms of birth control at all times.

If you plan to use oral contraceptives (birth control pills) while taking isotretinoin, tell your doctor the name of the pill you will use. Isotretinoin interferes with the action of micro-dosed progestin (‘minipill’) oral contraceptives (Ovrette, Micronor, Nor-QD). Do not use this type of birth control while taking isotretinoin.

If you plan to use hormonal contraceptives (birth control pills, patches, implants, injections, rings, or intrauterine devices), be sure to tell your doctor about all the medications, vitamins, and herbal supplements you are taking. Many medications interfere with the action of hormonal contraceptives. Do not take St. John’s wort if you are using any type of hormonal contraceptive.

You must have two negative pregnancy tests before you can begin to take isotretinoin. Your doctor will tell you when and where to have these tests. You will also need to be tested for pregnancy in a laboratory each month during your treatment, when you take your last dose and 30 days after you take your last dose.

You will need to contact the iPLEDGE system by phone or the internet every month to confirm the two forms of birth control you are using and to answer two questions about the iPLEDGE program. You will only be able to continue to get isotretinoin if you have done this, if you have visited your doctor to talk about how you are feeling and how you are using your birth control and if you have had a negative pregnancy test within the past 7 days.

Stop taking isotretinoin and call your doctor right away if you think you are pregnant, you miss a menstrual period, or you have sex without using two forms of birth control. If you become pregnant during your treatment or within 30 days after your treatment, your doctor will contact the iPLEDGE program, the manufacturer of isotretinoin, and the Food and Drug Administration (FDA). You will also talk with a doctor who specializes in problems during pregnancy who can help you make choices that are best for you and your baby. Information about your health and your baby’s health will be used to help doctors learn more about the effects of isotretinoin on unborn babies.

For male patients:

A very small amount of isotretinoin will probably be present in your semen when you take prescribed doses of this medication. It is not known if this small amount of isotretinoin may harm the fetus if your partner is or becomes pregnant. Tell your doctor if your partner is pregnant, plans to become pregnant, or becomes pregnant during your treatment with isotretinoin.

How does isotretinoin work?

Isotretinoin is an orally administered systemic retinoid. At a pharmacologic strength of 0.5 to 1.0 mg/kg per day, isotretinoin is an effective acne therapy. While the exact mechanism of action is unknown, at pharmacologic doses isotretinoin inhibits sebaceous gland function and keratinization. The drug has been observed to reduce both the sebaceous gland size and sebum production.

In neuroblastoma (off-label use), isotretinoin has been shown to decrease cell proliferation and induce differentiation 2.

Isotretinoin special precautions

Before using 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; 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.

Isotretinoin interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Chlortetracycline
  • Demeclocycline
  • Desogestrel
  • Dienogest
  • Doxycycline
  • Drospirenone
  • Estradiol Cypionate
  • Estradiol Valerate
  • Ethinyl Estradiol
  • Ethynodiol Diacetate
  • Etonogestrel
  • Levonorgestrel
  • Lymecycline
  • Meclocycline
  • Medroxyprogesterone Acetate
  • Mestranol
  • Methacycline
  • Minocycline
  • Norelgestromin
  • Norethindrone
  • Norgestimate
  • Norgestrel
  • Oxytetracycline
  • Rolitetracycline
  • Sarecycline
  • Tetracycline

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Alcoholism, severe or
  • Allergy to aspirin, history of or
  • Diabetes or
  • Metabolism disorder, family history of or
  • Severe weight problems—Use with caution. May increase risks for more serious problems.
  • Anorexia (eating disorder) or
  • Epiphyseal closure, premature or
  • Osteomalacia (softening of the bones) or
  • Osteoporosis (brittle bones), childhood or family history of or
  • Other bone disorders or diseases—Use with caution. It is not known whether this medicine affects bone loss.
  • Asthma or
  • Depression, history of or
  • Eye or vision problems or
  • Hearing problems or
  • Heart disease or
  • Hepatitis or
  • Hypertriglyceridemia (high triglycerides in the blood) or
  • Liver disease (eg, hepatitis) or
  • Pancreatitis (swelling of the pancreas) or
  • Pseudotumor cerebri (swelling in the brain) or
  • Psychosis (mental illness), history of or
  • Vitamin A overdose (too much vitamin A in the body)—Use with caution. May make these conditions worse.
    • Kidney disease or
    • Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Isotretinoin and pregnancy

Taking isotretinoin during pregnancy increases the risk of:

  • Miscarriage. This is when a baby dies in the womb before 20 weeks of pregnancy.
  • Premature birth. This is birth that happens too early, before 37 weeks of pregnancy.
  • Your baby having birth defects. Birth defects are health conditions that are present at birth that change the shape or function of one or more parts of the body. They can cause problems in overall health, how the body develops, or in how the body works.
  • Your baby having intellectual and developmental disabilities later in life. These are problems with how the brain works that can cause a person to have trouble or delays in physical development, learning, communicating, taking care of himself or getting along with others.

Birth defects that can be caused by isotretinoin include:

  • Cleft palate and other birth defects of the face. Cleft palate is when a baby’s palate (roof of the mouth) doesn’t form completely and has an opening in it.
  • Congenital heart defects. These are heart conditions that can affect the heart’s shape or how it works, or both.
  • Ear problems. Some babies also are born with small ears or are born missing ears. Some babies have hearing loss.
  • Eye problems. Some babies have microphthalmia, a condition that happens when one or both eyeballs are very small. It may lead to vision loss. Some babies are born missing eyes.
  • Hydrocephalus. This is fluid buildup in the brain. Extra fluid can cause the head to swell and put too much pressure on the brain. Hydrocephalus can cause intellectual disabilities. In some cases, a surgeon needs to drain the extra fluid from a baby’s brain.
  • Microcephaly. Babies born with microcephaly have a smaller-than-normal head because the brain doesn’t develop properly or has stopped growing. Babies with microcephaly may have intellectual and developmental disabilities, hyperactivity (trouble sitting still or paying attention), short height, seizures and problems with coordination and balance.
  • Small or missing thymus gland. This gland is in the upper chest. It makes white blood cells to protect the body from infection.

How can you prevent birth defects from isotretinoin?

Because isotretinoin can be so harmful to a developing baby, both women and men must register with the iPLEDGE program before they can take it. iPLEDGE is sponsored by the company that makes isotretinoin. iPLEDGE is approved by the Food and Drug Administration (also called FDA), the government agency that checks the safety of medicine and food in this country.

Both men and women who take isotretinoin must agree to follow strict iPLEDGE rules to help prevent pregnant women and women who may become pregnant from having contact with isotretinoin. Only doctors and pharmacists who are registered in the program may prescribe and give isotretinoin to patients.

If you’re taking isotretionoin, you must agree to use two different forms of effective birth control. Your doctor can help you choose two effective forms of birth control that work together. You also must take regular pregnancy tests and agree not to get pregnant:

  • For at least 4 weeks before you start using the medicine
  • While taking the medicine
  • For at least 4 weeks after you stop using the medicine

Men who take isotretinoin can have it in their semen (fluid that contains sperm). Experts don’t know if semen with isotretinoin can lead to birth defects. Talk to your doctor if your partner takes isotretinoin and you’re planning to get pregnant.

What should you do if you’re taking isotretinoin and think you may be pregnant?

STOP taking the medicine right away. As soon as possible, call the health care provider who prescribed the isotretinoin and the health care provider who will be taking care of you during your pregnancy. Your health care team can talk with you about screening tests and ultrasounds. Ultrasound can detect many (but not all) birth defects. Ultrasound cannot tell if a child may have learning or developmental problems.

If you take isotretinoin, call your doctor right away if:

  • You think you’re pregnant.
  • You have a late, irregular or missed menstrual period.
  • You have a change in your menstrual bleeding.
  • You have sex without using two forms of effective birth control.
  • You have unprotected sex with a man taking isotretinoin.

If you get pregnant while taking isotretenoin, your doctor must call iPLEDGE and the FDA.

How long does isotretinoin stay in the body? How long after a woman stops taking isotretinoin should she wait to become pregnant?

It is recommended that a woman wait one month after stopping isotretinoin before trying to become pregnant. Usually, isotretinoin is no longer found in a woman’s blood 4-5 days after the last dose and most of its by-products should be gone within 10 days after the last dose. However, the time it takes isotretinoin to be cleared from the body can be longer in some people, which is why it is recommended to wait at least one month after stopping isotretinoin before trying to become pregnant.

Does exposure to isotretinoin cause an increased risk for miscarriage or infant death?

YES. The risk for having a miscarriage can be as high as 40% when a woman takes isotretinoin in early pregnancy.

Can taking isotretinoin during pregnancy cause birth defects?

YES. Isotretinoin causes birth defects in more than 35% of infants whose mothers take the drug during pregnancy. This risk applies even if the medication has been taken for a short time. Most of the infants with birth defects will have small or absent ears, hearing and eyesight problems. Life-threatening heart defects and fluid around the brain are other birth defects that have be seen in some infants. Some will have a small jaw, small head, cleft palate and some will be born with a small or missing thymus gland (a gland in our body that makes hormones).

Will taking isotretinoin have an effect on a baby’s behavior and development?

YES. Many of the exposed children will have moderate to severe behavioral problems and/or intellectual disability. These difficulties do not get noticed at birth, but are discovered in childhood. Other possible long-term effects on any exposed child are still unknown.

Can oral retinoids other than isotretinoin cause birth defects?

Yes. Other oral retinoids can cause birth defects similar to those caused by isotretinoin. There’s no program like iPLEDGE for other oral retinoids. But if you’re taking other oral retinoids, following the iPLEDGE rules can help prevent birth defects.

Oral retinoids include:

  • Acitretin (Soriatane®). This medicine treats severe psoriasis, a skin disease that causes itchy or sore patches of thick, red skin with silvery scales.
  • Tretinoin (Vesanoid®). This medicine treats a type of blood cancer called acute promyelocytic leukemia.
  • Bexarotene (Targretin®). This medicine treats a type of blood cancer called T-cell lymphoma.

Can topical retinoids affect your baby during pregnancy?

Topical retinoids are medicines you put directly on your skin. We don’t know if topical retinoids are safe during pregnancy. But small amounts may be absorbed by the skin, so it’s best to avoid them. Topical retinoids include tretinoin, which treats acne and other skin problems. Tretinoin is sold as these brand names: Altinac®, Atralin®, Avita®, Retin-A®, Renova® and TretinX®.

Is it safe to breastfeed while using isotretinoin or other retinoids?

Experts are not sure if using isotretinoin or other retinoids while breastfeeding is safe for your baby. There have been no studies looking at taking isotretinoin during breastfeeding. It is not known if isotretinoin can get into breast milk but other similar medications can. It’s best not to breastfeed while using these medicines.

Experts do not know what effect exposure to isotretinoin through the breast milk can have on a nursing infant. Until more is known, women who are breastfeeding should not take isotretinoin. Be sure to talk to your health care provider about all your breastfeeding questions.

Can vitamin A cause birth defects?

Your baby needs vitamin A for healthy growth and development during pregnancy. But too much may cause birth defects.

Your body makes its own vitamin A when you eat certain yellow and green vegetables. This form of vitamin A is safe during pregnancy. Getting too much preformed vitamin A can cause birth defects. Preformed vitamin A is found in foods like meat (especially liver), fish, eggs, poultry and dairy foods.

Talk to your health care provider about getting the right amount of vitamin A from healthy eating and your prenatal vitamin.

Can isotretinoin make it more difficult to get pregnant?

Women who are trying to become pregnant should not be taking isotretinoin. There have been reports of irregular menstrual periods in some women taking isotretinoin. There are no reports of problems getting pregnant while taking isotretinoin.

What if the father of the baby takes isotretinoin?

Isotretinoin does not appear to affect sperm. There have been a few reports of erectile dysfunction and ejaculatory failure in men taking isotretinoin, but there have been no reports of isotretinoin causing infertility in men. There are no studies looking at risks for birth defects when the father takes isotretinoin. In general, exposures that fathers have are unlikely to increase risks to a pregnancy.

Isotretinoin vs Tretinoin

Tretinoin is used to treat acute promyelocytic leukemia (a type of cancer in which there are too many immature blood cells in the blood and bone marrow) in people who have not been helped by other types of chemotherapy or whose condition has improved but then worsened following treatment with other types of chemotherapy. Tretinoin is used to produce remission (a decrease or disappearance of signs and symptoms of cancer) of acute promyelocytic leukemia, but other medications must be used after treatment with tretinoin to prevent the cancer from returning. Tretinoin is in a class of medications called retinoids. It works by slowing or stopping the growth of cancer cells by causing immature blood cells to develop into normal blood cells.

Tretinoin comes as a capsule to take by mouth. It is usually taken twice a day for up to 90 days. Take tretinoin at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take tretinoin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Continue to take tretinoin even if you feel well. Do not stop taking tretinoin without talking to your doctor.

Tretinoin topical (for the skin) (Retin-A® and other brand names) is used as a cream or a gel on the skin to treat acne, to smooth rough facial skin, and to reduce the appearance of fine wrinkles and mottled skin discoloration. Tretinoin is related to Vitamin A and isotretinoin.

Tretinoin IMPORTANT WARNING

Tretinoin may cause severe side effects. Tretinoin should be given only under the supervision of a doctor who has experience in treating people who have leukemia (cancer of the white blood cells) and in a hospital where patients can be monitored for severe side effects and treated if these side effects occur.

Tretinoin may cause a serious or life-threatening group of symptoms called retinoic acid-APL(RA-APL) syndrome. Your doctor will monitor you carefully to see whether you are developing this syndrome. If you experience any of the following symptoms, call your doctor immediately: fever; weight gain; swelling of the arms, hands, feet, ankles, or lower legs; shortness of breath; labored breathing; wheezing; chest pain; or cough. At the first sign that you are developing RA-APL syndrome, your doctor will prescribe one or more medications to treat the syndrome.

Tretinoin may cause a rapid increase in the number of white blood cells in the body. This is associated with a higher risk of life-threatening side effects. If you have a very high number of white blood cells before you begin tretinoin treatment, or if you have an increase in the number of white blood cells during your treatment with tretinoin, expecially if you experience any of the symptoms of RA-APL syndrome, your doctor may prescribe one or more medications to treat or prevent the increase in white blood cells.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body’s response to tretinoin.

Talk to your doctor about the risk(s) of taking tretinoin.

For female patients:

Tretinoin must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that tretinoin will cause the baby to be born with birth defects (physical problems that are present at birth).

If you can become pregnant, you will need to avoid pregnancy during your treatment with tretinoin. You must use two acceptable forms of birth control during your treatment and for 1 month after your treatment, even if you have infertility (difficulty becoming pregnant) or have experienced menopause (‘change of life’; end of monthly menstrual periods). You must use these two forms of birth control at all times unless you can promise that you will not have any sexual contact with a male for 1 month after your treatment. Your doctor will tell you which forms of birth control are acceptable, and will give you full information about birth control.

If you plan to use oral contraceptives (birth control pills) while taking tretinoin, tell your doctor the name of the pill you will use. Microdosed progestin (‘minipill’) oral contraceptives (Ovrette, Micronor, Nor-D) may not be an effective form of birth control for people who are taking tretinoin.

You must have a negative pregnancy test within 1 week before you begin to take tretinoin. You will also need to be tested for pregnancy in a laboratory each month during your treatment. Tell your doctor immediately if you think you might be pregnant at any time during your treatment with tretinoin.

Isotretinoin dosage

The dose of isotretinoin will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (capsules):
    • For acne:
      • Adults and children 12 years of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 0.5 to 1 milligram (mg) per kilogram (kg) of body weight per day, taken as 2 divided doses for 15 to 20 weeks. Your doctor may adjust your dose as needed.
      • Children younger than 12 years of age—Use and dose must be determined by your doctor.

Adult dose for Acne

Use: Treatment of severe recalcitrant nodular acne in patients who are unresponsive to conventional therapy, including systemic antibiotics

  • Maintenance dose: 0.25 to 0.5 mg/kg orally 2 times a day
  • Maximum dose: Up to 2 mg/kg/day
  • Duration of therapy: Up to 20 weeks

Comments:

  • Patients should take some formulations of this drug with food.
  • Prior to increasing the dose, patients should be asked about their compliance with treatment (e.g., taking this drug with food).
  • Patients with very severe acne, scarring, or primary manifestations on the trunk may require 2 mg/kg/day dosing.
  • Any patient requesting refills requires a new prescription and a new authorization from the iPLEDGE program.
  • The safety and efficacy of once a day dosing has not been established; thus, once a day dosing is not recommended.

Pediatric dose for Acne

Use: Treatment of severe recalcitrant nodular acne in patients who are unresponsive to conventional therapy, including systemic antibiotics

12 years or older:

  • Maintenance dose: 0.25 to 0.5 mg/kg orally 2 times a day
  • Maximum dose: 2 mg/kg/day
  • Duration of therapy: Up to 20 weeks

Comments:

  • Patients should take some formulations of this drug with food.
  • Prior to increasing the dose, patients should be asked about their compliance with treatment (e.g., taking this drug with food).
  • Patients with very severe acne, scarring, or primary manifestations on the trunk may require 2 mg/kg/day dosing.
  • Any patient requesting refills requires a new prescription and a new authorization from the iPLEDGE program.
  • The safety and efficacy of once a day dosing has not been established; thus, once a day dosing is not recommended.

Renal dose adjustments

  • Data not available

Liver dose adjustments

  • Suspected hepatitis or patients with liver function test elevations that do not normalize: Discontinue use; etiologies should be further investigated.

Dose Adjustments

  • Patients may discontinue treatment if the total nodule count has reduced by at least 70% before completing the 15 to 20-week treatment.

What should I do if I forget a dose?

Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Isotretinoin side effects

Isotretinoin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • red, cracked, and sore lips
  • dry skin, eyes, mouth, or nose
  • nosebleeds
  • changes in skin color
  • peeling skin on the palms of the hands and soles of the feet
  • changes in the nails
  • slowed healing of cuts or sores
  • bleeding or swollen gums
  • hair loss or unwanted hair growth
  • sweating
  • flushing
  • voice changes
  • tiredness
  • cold symptoms

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, stop taking isotretinoin and call your doctor or get emergency medical treatment immediately:

  • headache
  • blurred vision
  • dizziness
  • nausea
  • vomiting
  • seizures
  • slow or difficult speech
  • weakness or numbness of one part or side of the body
  • stomach pain
  • chest pain
  • difficulty swallowing or pain when swallowing
  • new or worsening heartburn
  • diarrhea
  • rectal bleeding
  • yellowing of the skin or eyes
  • dark colored urine
  • back, bone, joint or muscle pain
  • muscle weakness
  • difficulty hearing
  • ringing in the ears
  • vision problems
  • painful or constant dryness of the eyes
  • unusual thirst
  • frequent urination
  • trouble breathing
  • fainting
  • fast or pounding heartbeat
  • red, swollen, itchy, or teary eyes
  • fever
  • rash
  • peeling or blistering skin, especially on the legs, arms, or face
  • sores in the mouth, throat, nose, or eyes
  • red patches or bruises on the legs
  • swelling of the eyes, face, lips, tongue, throat, arms, hands, feet, ankles, or lower legs
  • difficulty swallowing or pain when swallowing

Isotretinoin may cause the bones to stop growing too soon in teenagers. Talk to your child’s doctor about the risks of giving this medication to your child.

Isotretinoin may cause other side effects. Call your doctor if you have any unusual problems while taking isotretinoin.

Symptoms of overdose may include the following:

  • vomiting
  • flushing
  • severe chapped lips
  • stomach pain
  • headache
  • dizziness
  • loss of coordination

Anyone who has taken an overdose of isotretinoin should know about the risk of birth defects caused by isotretinoin and should not donate blood for 1 month after the overdose. Pregnant woman should talk to their doctors about the risks of continuing the pregnancy after the overdose. Women who can become pregnant should use two forms of birth control for 1 month after the overdose. Men whose partners are or may become pregnant should use condoms or avoid sexual contact with that partner for 1 month after the overdose because isotretinoin may be present in the semen.

  1. Current use and future potential role of retinoids in dermatology. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC. Drugs. 1997 Mar; 53(3):358-88.[↩]
  2. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R. Guidelines of care for the management of acne vulgaris. J. Am. Acad. Dermatol. 2016 May;74(5):945-73.e33[↩][↩][↩]

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