Instructions for use
Isotretinoin is a drug with a strong teratogenic effect. If pregnancy occurs at a time when a woman orally takes isotretinoin (at any dose or even a short time), there is a very high risk of having a baby with developmental disabilities.
Accutane is contraindicated in women of childbearing age, unless a woman’s condition satisfies all of the following criteria:
she must have a severe form of acne that is resistant to the usual methods of treatment; she must understand and follow the instructions of the doctor; she should be informed by the doctor about the danger of pregnancy in the course of treatment with Accutane within one month after it and urgent consultation if a pregnancy is suspected; she should be warned about the possible ineffectiveness of contraception; it must confirm that it understands the essence of the precautions; she must understand the need and continuously use effective methods of contraception for one month before treatment with Accutane, during treatment and for one month after its termination (see the section “Interaction with other drugs”); It is desirable to use simultaneously 2 different methods of contraception, including barrier; she must have received a negative result of a reliable pregnancy test within 11 days before the start of the drug; pregnancy test is strongly recommended to be carried out monthly during treatment and 5 weeks after the end of therapy; she should start treatment with Accutane only for 2-3 days of the next normal menstrual cycle; she must understand the need for compulsory visits to the doctor every month; when treating for the recurrence of the disease, she should constantly use the same effective methods of contraception for one month before starting treatment with Accutane, during treatment and for one month after its completion, as well as undergo the same reliable pregnancy test; She must fully understand the need for precautions and confirm her understanding and desire to use reliable methods of contraception, which the doctor explained to her.
The use of contraceptives according to the above instructions during treatment with isotretinoin should be recommended even to women who usually do not use contraceptive methods due to infertility (except for patients who have undergone hysterectomy), amenorrhea, or who report that they are not sexually active.
The physician must be sure that:
The patient has a severe form of acne (nodular-cystic, conglobate acne or acne with the risk of scarring); acne that is not amenable to other therapies;
a negative result of a reliable pregnancy test was obtained before the start of the drug intake, during therapy and 5 weeks after the end of therapy; the dates and results of the pregnancy test must be documented;
the patient uses at least 1, preferably 2 effective methods of contraception, including a barrier method, within one month before the start of treatment with Accutane, during treatment and within a month after its termination;
the patient is able to understand and fulfill all the above requirements for the prevention of pregnancy;
the patient meets all the above conditions.
In accordance with existing practice, a pregnancy test with a minimum sensitivity of 25 mME / ml should be carried out in the first 3 days of the menstrual cycle:Before initiating therapy:
To exclude a possible pregnancy before the start of contraception, the result and the date of the initial pregnancy test must be recorded by a doctor. In patients with irregular menstruation, the time of the pregnancy test depends on sexual activity, it should be carried out 3 weeks after unprotected intercourse. The physician should inform the patient about contraceptive methods.
A pregnancy test is performed on the day Accutane is prescribed or 3 days before the patient's visit to the doctor. The specialist should register the test results. The drug can only be prescribed to patients who receive effective contraception for at least 1 month prior to the start of therapy with the drug.
During therapy:The patient should visit the doctor every 28 days. The need for monthly pregnancy testing is determined in accordance with local practice and taking into account sexual activity, previous violations of the menstrual cycle. If there is evidence, a pregnancy test is conducted on the day of the visit or three days before the visit to the doctor, the test results should be recorded.
End of therapy:5 weeks after the end of therapy, a test is performed to rule out pregnancy.
A prescription for Accutane for a woman capable of childbearing can be prescribed only for 30 days of treatment, the continuation of therapy requires a new prescription of the drug by a doctor. We recommend a pregnancy test, prescription and receiving the drug in one day.
To help doctors, pharmacists and patients avoid the risk of Accutane exposure to the fetus, the manufacturing company created a Pregnancy Protection Program, aimed at warning about the teratogenicity of the drug and emphasizing the absolutely mandatory use of reliable contraceptive measures for women of childbearing age. The program contains the following materials: for doctors:
a guide for the doctor on the prescription of Accutane for women; patient informed consent form; form of accounting for the purpose of the drug to women. For the patient: patient information leaflet; what you need to know about contraception.
Full information on teratogenic risk and strict adherence to measures to prevent pregnancy should be provided to both men and women.
Existing evidence suggests that in women, exposure to a drug that comes from the semen and seminal fluid of men who take Accutane is not sufficient for the teratogenic effects of Accutane to occur. Men should exclude the possibility of taking the drug by other persons, especially women.
If, despite the precautions taken, during pregnancy with Accutane or within a month after its termination the pregnancy nevertheless occurred, there is a high risk of very severe fetal malformations (in particular, from the central nervous system, heart and large blood vessels) . In addition, the risk of miscarriage increases. In the event of pregnancy, treatment with Accutane is discontinued. The feasibility of its preservation should be discussed with a physician specializing in teratology.
Severe congenital malformations of the fetus in humans associated with Accutane prescription, including hydrocephalus, microcephaly, cerebellar malformations, anomalies of the external ear (microtia, narrowing or absence of the external auditory canal), microphthalmia, cardiovascular anomalies (tetrad Fallot, transposition of great vessels, defects of partitions), facial malformations (cleft palate), thymus, parathyroid gland pathology.
Since isotretinoin has a high lipophilicity, it is very likely that it passes into breast milk. Due to possible side effects, Accutane cannot be administered to nursing mothers.
Dosage and administration
Inside, with a meal once or twice a day. The therapeutic efficacy of Accutane and its side effects are dose dependent and vary in different patients. This dictates the need for individual dose selection during treatment.
Treatment with Accutane should begin with a dose of 0.5 mg / kg per day. In most patients, the dose ranges from 0.5 to 1.0 mg / kg of body weight per day. Patients with very severe forms of the disease or with acne torso may require higher daily doses - up to 2.0 mg / kg. It is proved that the frequency of remission and prevention of recurrence is optimal when using a course dose of 120-150 mg / kg (per course of treatment), therefore the duration of therapy in specific patients varies depending on the daily dose. Complete acne remission can often be achieved within 16-24 weeks of treatment. In patients who very poorly tolerate the recommended dose, treatment can be continued at a lower dose, but it can be carried out longer.
In most patients, acne completely disappears after a single course of treatment. With a clear relapse, a repeated course of treatment with Accutane is indicated in the same daily and course dose as the first. Since the improvement can continue up to 8 weeks after discontinuation of the drug, a second course should be prescribed not earlier than the end of this period.
Dosing in special cases.In patients with severe renal insufficiency, treatment should begin with a lower dose (for example, 10 mg / day) and further increase to 1 mg / kg / day or maximum tolerated (but not more than the maximum daily dose of 1 mg / kg). The daily dose should be rounded down to the nearest smaller number of whole capsules.
Most of the side effects of Accutane are dose dependent. As a rule, when prescribing the recommended doses, the ratio of benefits and risks, taking into account the severity of the disease, is acceptable for the patient. Usually, side effects are reversible after dose adjustment or drug withdrawal, but some may persist after stopping treatment.
Symptoms associated with hypervitaminosis A: dry skin, mucous membranes, incl. lips (cheilitis), nasal cavity (bleeding), laryngopharynx (hoarseness), eyes (conjunctivitis, reversible corneal clouding and intolerance to contact lenses).Skin and appendages: rash, pruritus, facial erythema / dermatitis, sweating, pyogenic granuloma, paronychia, onychodystrophy, increased proliferation of granulation tissue, persistent hair thinning, reversible hair loss, fulminant form of acne, hirsutism, hyperpigmentation, photosensitivity, photoallergy, easy traumatized skin, peeling skin of palms and soles. At the beginning of treatment, acne may worsen, lasting for several weeks.
Musculoskeletal system: muscle pain with increased activity of creatine phosphokinase (CK) in serum or without it, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, decrease in bone density, premature closure of epiphyseal growth zones, other changes in bones, tendinitis .
Central nervous system and mental health: impaired behavior, depression, suicidal attempts, suicide, psychosis, excessive fatigue, headache, increased intracranial pressure ("brain pseudo-tumor": headache, nausea, vomiting, blurred vision, swelling of the optic nerve) convulsions.
Sense organs: impaired visual acuity, photophobia, impaired dark adaptation (reduced sharpness of twilight vision), impaired color perception (taking place after discontinuation of the drug), lenticular cataract, keratitis, blepharitis, conjunctivitis, eye irritation, xerophthalmia, hearing loss at certain sound frequencies.
Gastrointestinal tract: nausea, diarrhea, inflammatory bowel disease (colitis, ileitis), bleeding, dryness of the oral mucosa, bleeding from the gums, gum inflammation; pancreatitis (especially with concomitant hypertriglyceridemia above 800 mg / dL), including with a fatal outcome.
Transient and reversible increase in liver transaminases, hepatitis. In many of these cases, the changes did not go beyond the limits of the norm and returned to the original indicators in the course of treatment, but in some situations it was necessary to reduce the dose or cancel Accutane.
Respiratory system: bronchospasm (more often in patients with a history of bronchial asthma).
Blood system: anemia, decrease in hematocrit, leukopenia, neutropenia, increase or decrease in the number of platelets, increase in erythrocyte sedimentation rate (ESR).
Laboratory indicators: hypertriglyceridemia, hypercholesterolemia, hyperuricemia, a decrease in the concentration of high-density lipoproteins, hyperglycemia. While taking Accutane cases of newly diagnosed diabetes mellitus were reported. In some patients, especially those engaged in intense physical activity, isolated cases of an increase in the activity of CK in serum have been described.
Immune system: local or systemic infections caused by gram-positive pathogens (Staphylococcus aureus).
Other: lymphadenopathy, hematuria, proteinuria, vasculitis (Wegener's granulomatosis, allergic vasculitis), systemic hypersensitivity reactions, glomerulonephritis, back pain.
Post-marketing surveillance.During post-marketing follow-up with Accutane, cases of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis are described (see also the section “Special Instructions”). When Accutane was used, especially in patients who had performed intense physical exertion, serious cases of rhabdomyolysis were reported, often resulting in hospitalization. These phenomena in all cases safely resolved. Cases of development of renal failure is not registered.
Overdose.In case of an overdose, signs of hypervitaminosis A may appear. In the first few hours after the overdose, gastric lavage may be necessary.
Accutane should be prescribed only by physicians, preferably dermatologists, who are experienced in using systemic retinoids and who are aware of the risk of drug teratogenicity. Patients, both female and male, need to issue a copy of the patient information leaflet. In order to avoid accidental exposure of the drug to the body of other people, patients who receive or shortly before that (1 month) received Accutane should not be donated blood.
It is recommended to monitor liver function and liver enzymes before treatment, 1 month after its onset, and then every 3 months or as indicated. A transient and reversible increase in hepatic transaminases is noted, in most cases within normal limits. If the activity of hepatic transaminases exceeds the norm, it is necessary to reduce the dose of the drug or cancel it.
It is recommended to monitor liver function and liver enzymes before treatment, 1 month after its onset, and then every 3 months or as indicated. A transient and reversible increase in hepatic transaminases is noted, in most cases within normal limits. If the activity of hepatic transaminases exceeds the norm, it is necessary to reduce the dose of the drug or cancel it. You should also determine the concentration of lipids in the serum on an empty stomach before treatment, 1 month after the start, and then every 3 months or according to indications. Usually, lipid concentrations are normalized after dose reduction or withdrawal of the drug, as well as diet. It is necessary to control the clinically significant increase in the concentration of triglycerides, since their elevation above 800 mg / dL or 9 mmol / L may be accompanied by the development of acute pancreatitis, possibly with a fatal outcome. If persistent hypertriglyceridemia or pancreatitis symptoms, Accutane should be canceled.
In rare cases, patients treated with Accutane described depression, psychotic symptoms, and very rarely suicidal attempts and suicide. Although their causal relationship with the use of the drug has not been established, special care must be taken in patients with depression in history and all patients should be monitored for depression during treatment with the drug, if necessary, referring them to the appropriate specialist. However, withdrawal of Accutane may not lead to the disappearance of symptoms and may require further observation and treatment by a specialist. In rare cases, at the beginning of therapy, the aggravation of acne is noted, which disappears within 7-10 days without adjusting the dose of the drug.
A few years after Accutane was used for the treatment of dyskeratosis with a total dose rate and duration of therapy, higher than those recommended for acne therapy, bone changes developed, including premature closure of epiphyseal growth zones, hyperostosis, calcification of ligaments and tendons. Therefore, when prescribing a drug to any patient, you should first carefully evaluate the ratio of possible benefits and risks. Patients receiving Accutane are recommended to use moisturizing ointment or body cream, lip balm to reduce dry skin and mucous membranes at the beginning of therapy.
During post-marketing follow-up with Accutane, cases of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis are described. These phenomena can be serious and lead to disability, life-threatening conditions, hospitalization or fatal outcome. Patients receiving Accutane need careful monitoring in order to identify severe skin reactions and, if necessary, decide on the abolition of the drug. While taking Accutane, pains in muscles and joints, increased serum CPK activity, which may be accompanied by a decrease in tolerance to intense physical activity, are possible.
Rare cases of anaphylactic reactions that occurred only after previous external use of retinoids have been described. Severe allergic reactions dictate the need for drug withdrawal and careful monitoring of the patient. Patients from the high-risk group (diabetes, obesity, chronic alcoholism, or impaired fat metabolism) may need more frequent laboratory monitoring of glucose and lipid concentrations when treated with Accutane.
If diabetes is present or suspected, a more frequent determination of glycemia is recommended. Drug exposure to the environment should be kept to a minimum. Do not dispose of Accutane with wastewater or with household waste. If possible, use special systems for the disposal of drugs.