ISOTRETINOIN

Posology Isotretinoin should only be prescribed by or under the supervision of physicians with expertise in the use of systemic retinoids for the treatment of severe acne and a full understanding of the risks of isotretinoin therapy and monitoring requirements.

The capsules should be taken with food once or twice daily. 5 mg/kg daily. The therapeutic response to isotretinoin and some of the adverse effects are dose- related and vary between patients. This necessitates individual dosage adjustment during therapy.

0 mg/kg per day. Long-term remission and relapse rates are more closely related to the total dose administered than to either duration of treatment or daily dose. It has been shown that no substantial additional benefit is to be expected beyond a cumulative treatment dose of 120-150 mg/kg.

The duration of treatment will depend on the individual daily dose. A treatment course of 16-24 weeks is normally sufficient to achieve remission. In the majority of patients, complete clearing of the acne is obtained with a single treatment course.

In the event of a definite relapse a further course of isotretinoin therapy may be considered using the same daily dose and cumulative treatment dose. As further improvement of the acne can be observed up to 8 weeks after discontinuation of treatment, a further course of treatment should not be considered until at least this period has elapsed.

g. 10 mg/day). 4). Paediatric Population Isotretinoin should not be used for the treatment of prepubertal acne and is not recommended in children less than 12 years of age due to a lack of data on efficacy and safety. In patients under 18 years of age two independent prescribers must agree that there is no other appropriate effective treatment before initiation of isotretinoin therapy.

Patients with intolerance In patients who show severe intolerance to the recommended dose, treatment may be continued at a lower dose with the consequences of a longer therapy duration and a higher risk of relapse. In order to achieve the maximum possible efficacy in these patients the dose should normally be continued at the highest tolerated dose.

Method of administration For oral use.

Summary of safety profile Some of the side effects associated with the use of isotretinoin are dose- related. The side effects are generally reversible after altering the dose or discontinuation of treatment, however some may persist after treatment has stopped.

g. of the lips (cheilitis), the nasal mucosa (epistaxis) and the eyes (conjunctivitis), Tabulated list of adverse reactions The incidence of the adverse reactions calculated from pooled clinical trial data involving 824 patients and from post-marketing data are presented in the table below.

The adverse reactions are listed below by MedDRA system organ class (SOC) and categories of frequency. Frequency categories are defined as Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) and not known (cannot be estimated from the available data).

Within each frequency grouping and SOC, adverse reactions are presented in order of decreasing seriousness. 4) Hepatitis Skin and subcutaneous tissue disorders Pruritus, rash erythematous, dermatitis, cheilitis, dry skin, localised exfoliation, skin fragility (risk of frictional trauma) Alopecia Acne fulminans, acne aggravated (acne flare), erythema (facial), exanthema, hair disorders, hirsutism, nail dystrophy, paronychia, photosensitivity reaction, pyogenic granuloma, skin hyperpigmentation, sweating increased Erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis Musculo-skeletal and connective tissue disorders Arthralgia, myalgia, back pain (particularly in children and adolescent patients) Arthritis, calcinosis (calcification of ligaments and tendons), epiphyses premature fusion, exostosis (hyperostosis), reduced bone density, tendonitis Rhabdomyolysis, Sacroiliitis Renal and urinary disorders Glomerulonephritis Urethritis Reproductive system and breast disorders Sexual dysfunction including erectile dysfunction and decreased libido, gynaecomastia, vulvovaginal dryness, orgasm abnormal, genital hypoaesthesia General disorders and administration site conditions Granulation tissue (increased formation of), malaise Investigations Blood triglycerides increased, high density lipoprotein decreased Blood cholesterol increased, blood glucose increased, haematuria, proteinuria Blood creatine phosphokinase increased * cannot be estimated from the available data.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Teratogenic effects Isotretinoin is a powerful human teratogen inducing a high frequency of severe and life threatening birth defects. Isotretinoin is strictly contraindicated in: − Pregnant women − Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met.

1). • The potential for pregnancy must be assessed for all female patients. • She understands the teratogenic risk. • She understands the need for rigorous follow-up on a monthly basis. • She understands and accepts the need for effective contraception, without interruption, 1 month before starting treatment, throughout the entire duration of treatment and for 1 month after the end of treatment.

e. a user- independent form) or two complementary user-dependent forms of contraception should be used. • Individual circumstances should be evaluated in each case, when choosing the contraception method, involving the patient in the discussion, to guarantee her engagement and compliance with the chosen measures.

• Even if she has amenorrhea she must follow all of the advice on effective contraception. • She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy or if she might be pregnant.

• She understands the need and accepts to undergo regular pregnancy testing before, ideally monthly during treatment and 1 month after stopping treatment. • She has acknowledged that she has understood the hazards and necessary precautions associated with the use of isotretinoin.

These conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy. The prescriber must ensure that: • The patient complies with the conditions for pregnancy prevention as listed above, including confirmation that she has an adequate level of understanding.

• The patient has acknowledged the aforementioned conditions. e. a user independent form) or two complementary user-dependent forms of contraception, for at least 1 month prior to starting treatment and is continuing to use effective contraception throughout the treatment period and for at least 1 month after cessation of treatment.

• Negative pregnancy test results have been obtained before, during and 1 month after the end of treatment. The dates and results of pregnancy tests should be documented. If pregnancy occurs in a woman treated with isotretinoin, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice.

If pregnancy occurs after stopping treatment there remains a risk of severe and serious malformation of the foetus. This risk persists until the product has been completely eliminated, which is within one month following the end of treatment.

Contraception Female patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception. If the prescribing physician is not in a position to provide such information the patient should be referred to the relevant healthcare professional.

e. a user independent form), or two complementary user- dependent forms of contraception. Contraception should be used for at least 1 month prior to starting treatment, throughout treatment and continue for at least 1 month after stopping treatment with isotretinoin, even in patients with amenorrhea.

Individual circumstances should be evaluated in each case, when choosing the contraception method involving the patient in the discussion, to guarantee her engagement and compliance with the chosen measures. Pregnancy testing According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25mIU/mL are recommended to be performed, as follows.

Prior to starting therapy At least one month after the patient has started using contraception, and shortly (preferably a few days) prior to the first prescription, the patient should undergo a medically supervised pregnancy test. This test should ensure the patient is not pregnant when she starts treatment with isotretinoin.

Follow-up visits Follow-up visits should be arranged at regular intervals, ideally monthly. The need for repeated medically supervised pregnancy tests every month should be determined according to local practice including consideration of the patient’s sexual activity, recent menstrual history (abnormal menses, missed periods or amenorrhea) and method of contraception.

Where indicated, follow-up pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber. End of treatment 1 month after stopping treatment, women should undergo a final pregnancy test.

Prescribing and dispensing restrictions For women of childbearing potential, the prescription duration of isotretinoin should ideally be limited to 30 days in order to support regular follow up, including pregnancy testing and monitoring.

Ideally, pregnancy testing, issuing a prescription and dispensing of isotretinoin should occur on the same day. Dispensing of isotretinoin should occur […]

Isotretinoin is contraindicated in women who are pregnant or breastfeeding. 6). 4). 1. Isotretinoin 10mg contains refined soya oil and partly hydrogenated soya oil. Therefore, Isotretinoin 10mg is contraindicated in patients allergic to peanut or soya.

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