Isotretinoin (Absorica) Risks, Warnings, and Complications

CONTRAINDICATED IN PREGNANCY: Isotretinoin is associated with an extremely high risk of life-threatening birth defects, miscarriage, premature births, and fetal demise when used during pregnancy. Due to the risk of severe birth defects, this medication is contraindicated in pregnant women. Major congenital malformations can occur with any amount of the medicine taken even for short periods. It is not possible to find out prenatally (before birth) if a fetus exposed to isotretinoin has been harmed. 

iPLEDGE PROGRAM: Because of the serious risk of harm to an unborn baby, isotretinoin is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program called the iPLEDGE REMS. This program requires female patients to:

Sign an informed consent stating your understanding of the risks of taking isotretinoin.

Obtain the medicine from a health care provider and pharmacy that is certified with the iPLEDGE program. 

See their doctor every month during treatment.

Obtain only a 30-day supply of isotretinoin at a time without any refill.

Have a pregnancy test in an approved lab each month and pick up their prescription within 7 days of the negative pregnancy test (if they are a woman with childbearing potential).

Pick up their prescription within 30 days of the doctor's visit (if they are a man or a woman who cannot become pregnant).

Have two negative serum pregnancy tests before starting treatment.

Use two acceptable forms of birth control (for example, combined hormonal contraceptives) for one month before starting isotretinoin, during treatment, and for one month after stopping isotretinoin. The mini pill (progestin-only) is not an acceptable form of contraception during isotretinoin treatment. Patients should give their doctor a list of all their medications if they are on combination oral contraceptives because some medications, dietary supplements, and herbal products can interfere with hormonal contraception.

You may be excused from meeting these conditions if you are a postmenopausal woman (you have not had a menstrual period for at least 12 months) or if you have had surgical removal of your uterus and both ovaries.

However, you must meet the conditions of the risk mitigation strategy REMS called iPLEDGE even if you have not started menstruating or have had a tubal ligation (tubes tied for contraception).

You should not donate blood while on isotretinoin and for one month after finishing treatment with this medicine.

Men who take isotretinoin may have small amounts of the drug in their semen. It is unclear if this can harm the baby if their partner becomes pregnant. 

If you become pregnant while on isotretinoin, discontinue the medicine immediately and contact your doctor. Your provider will refer you to a specialist who can counsel you about the possible adverse effects of suspected fetal exposure and help you make the best choice for you and your baby.

ABSORICA AND ABSORICA LD ARE NOT INTERCHANGEABLE: The bioavailability and recommended dosage of Absorica and Absorica LD are not the same. Therefore, you cannot substitute these two formulations, for example, 20 mg Absorica for 20 mg Absorica LD.

PSYCHIATRIC PROBLEMS: Isotretinoin can cause serious adverse reactions including depression, psychosis, aggressive and violent behaviors, and rarely, suicidal thoughts and behaviors. 

Tell your doctor if you have a psychiatric disorder before starting isotretinoin. Stop taking isotretinoin and call your healthcare provider if you notice any unusual changes in mood or behavior. Family members should be aware of the need to recognize psychiatric disorders. They should know how to contact the healthcare provider if a patient develops depression or other symptoms.

INTRACRANIAL HYPERTENSION: Isotretinoin has been linked to intracranial hypertension (pseudotumor cerebri) or increased pressure inside the skull. The risk is higher with tetracycline medication administered concomitantly. Tell your doctor immediately if you develop vision changes, headache, nausea, or vomiting while on isotretinoin. If you develop this complication, you may need to discontinue treatment.

SERIOUS SKIN REACTIONS: There are reports of erythema multiforme and severe skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after isotretinoin use. These adverse effects may require hospitalization, cause disability, and be fatal. Call your doctor immediately or seek emergency medical care if you develop a skin rash or blistering or peeling skin.

PANCREATITIS: Acute pancreatitis (inflammation of the pancreas) has been reported in isotretinoin therapy patients. This can occur in people with both elevated and normal serum triglyceride levels. Rarely, isotretinoin can cause fatal hemorrhagic pancreatitis. Seek immediate medical care if you develop symptoms of pancreatitis such as severe stomach pain, nausea, vomiting, fever, fast heartbeat, shortness of breath, or yellowing of the skin or eyes.

ELEVATED TRIGLYCERIDES: Lipid abnormalities, including dangerously high serum triglyceride levels above 800 mg/dL, have been reported in people treated with isotretinoin. Clinical trials have shown that high serum triglyceride levels can cause other changes in lipid levels. Patients usually experience a reversal in triglyceride levels once isotretinoin is stopped. Some people are able to reverse the elevation in triglycerides with weight loss and dietary restrictions. Your doctor may recommend a dosage reduction if you develop lipid abnormalities. 

Tell your doctor if you have other risk factors for elevated triglycerides, such as obesity, diabetes, excessive alcohol use, or a personal or family history of lipid metabolism disorders.

Keep all your medical and laboratory appointments while on this drug. Your healthcare provider may order lipid tests before initiating treatment and then regularly during treatment. The lipid response to treatment usually becomes known within 4 weeks.

HEARING IMPAIRMENT: There are reports of hearing impairment in patients who are on isotretinoin. This can persist after the drug is discontinued. Tell your doctor if you experience tinnitus (ringing in the ears) or hearing impairment. You will need to stop treatment with isotretinoin and see a specialist.

LIVER INJURY: There are reports of clinical hepatitis (liver inflammation) after isotretinoin use as well as elevations in liver enzymes. These changes may normalize after a dose reduction. If you continue to show signs of liver damage and your doctor suspects hepatitis, you may need to stop taking isotretinoin.

INFLAMMATORY BOWEL DISEASE (IBD): Isotretinoin has been linked to IBD, even in people who don’t have any prior history of intestinal disorders. The symptoms can persist after treatment with isotretinoin is stopped. Tell your doctor if you develop stomach pain, severe diarrhea, or rectal bleeding while on this medicine.

MUSCULOSKELETAL SYMPTOMS: Isotretinoin can negatively affect bone mineral density (BMD) in some people, leading to osteoporosis and an increased risk of bone fractures. Clinical trials have shown that BMD in the adolescent population does not recover even after treatment is stopped. There are also reports of osteoporosis, osteopenia, bone fractures, delayed fracture healing, skeletal hyperostosis, and premature epiphyseal closure in people taking isotretinoin or after stopping treatment with this drug.

Therefore, isotretinoin should be used with caution in people with a history of musculoskeletal disorders, eating disorders such as anorexia, and those on chronic treatment with other drugs that can also cause osteoporosis (for example, systemic corticosteroids and anticonvulsants). 

Tell your doctor without delay if you develop muscle weakness, muscle pain, joint pain, bone pain, or back pain while on this drug. You should know that high-dose, long-term, or multiple courses of isotretinoin may have a greater effect on bone metabolism. Do not take more than the recommended dose or use this medicine for longer than recommended by your healthcare provider.

EYE PROBLEMS: Stop taking isotretinoin and call your doctor if you develop any vision problems on isotretinoin. There are reports of corneal opacities, especially at higher doses in patients with keratinization disorders. These changes typically resolve after stopping isotretinoin. However, other changes like decreased night vision can persist after discontinuing isotretinoin. Other eye problems associated with isotretinoin include dry eyes and problems wearing contact lenses.

HYPERSENSITIVITY REACTIONS: Anaphylactic reactions (throat closing and difficulty breathing) and other allergic reactions including allergic vasculitis have been reported after isotretinoin use. Call your doctor immediately or seek emergency medical care if you develop a rash or red patches or bruises on your skin. A severe allergic reaction will require you to stop treatment with isotretinoin and receive appropriate medical care.

Note: The 25-mg Absorica capsule contains tartrazine dye (FD&C Yellow No. 5) which can cause allergic reactions (including asthma) in certain high-risk individuals. People with aspirin hypersensitivity are at a higher risk of this complication. The other dosage strengths of Absorica (10 mg, 20 mg, 30 mg, 35 mg, and 40 mg) and all the dosage strengths of Absorica LD do not contain this dye.

LABORATORY MONITORING: Scheduled pregnancy testing is necessary before starting isotretinoin, each month during treatment, and one month after stopping therapy. 

A pretreatment and follow-up fasting lipid panel is also obtained before starting isotretinoin. Do not drink alcohol for at least 36 hours before this lab test. 

Your doctor will also order liver function tests to check if liver enzymes are elevated (this can be a sign of liver damage). These blood tests will be performed periodically until your response to the drug is known. 

LABORATORY ABNORMALITIES: Isotretinoin use can cause problems with blood sugar control, including a new diagnosis of diabetes. Some patients develop changes in CPK levels with strenuous physical activity while on isotretinoin; however, the clinical significance of this change is unknown. There are also rare reports of rhabdomyolysis (severe muscle injury) with isotretinoin use, sometimes in association with vigorous physical activity.