NEOTIGASON

6). The capsules should be taken once daily with meals or with milk. There is a wide variation in the absorption and rate of metabolism of Acitretin. This necessitates individual adjustment of dosage. For this reason the following dosage recommendations can serve only as a guide.

Adults Initial daily dose should be 25mg or 30mg for 2 to 4 weeks. After this initial treatment period the involved areas of the skin should show a marked response and/or side-effects should be apparent. Following assessment of the initial treatment period, titration of the dose upwards or downwards may be necessary to achieve the desired therapeutic response with the minimum of side-effects.

The maintenance dose must be based on clinical efficacy and tolerability. In general, a daily dosage of 25 - 50mg taken for a further 6 to 8 weeks achieves optimal therapeutic results. However, it may be necessary in some cases to increase the dose up to a maximum of 75mg/day.

In patients with Darier’s disease a starting dose of 10mg may be appropriate. The dose should be increased cautiously as isomorphic reactions may occur. Therapy can be discontinued in patients with psoriasis whose lesions have improved sufficiently.

Relapses should be treated as described above. Patients with severe congenital ichthyosis and severe Darier's disease may require therapy beyond 3 months. The lowest effective dosage, not exceeding 50mg/day should be given. Continuous use beyond 6 months is contraindicated as only limited clinical data are available on patients treated beyond this length of time.

Elderly Dosage recommendations are the same as for other adults. Paediatric population In view of possible severe side-effects associated with long-term treatment, Acitretin is contraindicated in children unless, in the opinion of the physician, the benefits significantly outweigh the risks.

Acitretin should be used only when all alternative therapies have proved inadequate. The dosage should be established according to bodyweight. 5mg/kg. Higher doses (up to 1mg/kg daily) may be necessary in some cases for limited periods, but only up to a maximum of 35mg/day.

The maintenance dose should be kept as low as possible in view of possible long-term side-effects. Combination therapy Other dermatological therapy, particularly with keratolytics, should normally be stopped before administration of Acitretin.

However, the use of topical corticosteroids or bland emollient ointment may be continued if indicated. When Acitretin is used in combination with other types of therapy, it may be possible, depending on the individual patient's response, to reduce the dosage of Acitretin.

Method of administration Acitretin capsules are for oral administration.

). Treatment with high dose retinoids can cause mood changes including irritability, aggression and depression. Excipient(s) Sodium This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

3. An increased risk of hepatitis has been reported following the concomitant use of methotrexate and etretinate. 6. Interactions with combined estrogen/progestogen oral contraceptives have not been observed. In a study with healthy volunteers, concurrent intake of a single dose of acitretin together with alcohol led to the formation of etretinate which is highly teratogenic.

The mechanism of this metabolic process has not been defined, so it is not clear whether other interacting agents are also possible. Women of childbearing age must therefore not consume alcohol (in drinks, food or medicines) during treatment with acitretin and for 2 months after cessation of acitretin therapy.

2). In concurrent treatment with phenytoin, it must be remembered that Acitretin partially reduces the protein binding of phenytoin. The clinical significance of this is as yet unknown. g. digoxin, cimetidine) have not been observed to date.

Investigations into the effect of acitretin on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction. 6 Fertility, Pregnancy and lactation Women of childbearing potential / Contraception in males and females Acitretin is highly teratogenic.

Its use is contraindicated in women who might become pregnant during or within 3 years of the cessation of treatment. The risk of giving birth to a deformed child is exceptionally high if acitretin is taken before or during pregnancy, no matter for how long or at what dosage.

Acitretin is contraindicated in every woman of childbearing potential unless each of the following conditions is met: 1) The patient is suffering from a severe disorder of keratinisation which is resistant to standard therapies. 2) She can be relied on to understand and follow the physician’s instructions.

3) She is capable of taking the stipulated contraceptive measures reliably and without fail. 4) It is absolutely essential that every woman of childbearing potential who is to undergo treatment with acitretin uses effective contraception (preferably 2 complementary methods) without interruption for four weeks before, during and for 3 years after the discontinuation of treatment with acitretin.

The patient should be instructed to immediately contact a doctor in case of suspected pregnancy. Even female patients who normally do not practice contraception because of a history of infertility should be advised to do so, while taking Acitretin.

5) Therapy should not begin until the second or third day of the next normal menstrual period. 6) At the start of therapy, a negative pregnancy test result (minimum sensitivity of 25mIU/mL) must be obtained up to three days before the first dose is given.

During therapy, pregnancy tests should be arranged at 28-day intervals. A negative pregnancy test not older than 3 days is mandatory before prescription is made at these visits. After stopping therapy, pregnancy tests should be performed at 1-3 monthly intervals for a period of 3 years after the last dose is given.

7) Before therapy with acitretin is instituted, the physician must give patients of childbearing potential detailed information about the precautions to be taken, the risk of very severe foetal malformation, and the possible consequences if pregnancy occurs during the course of treatment with acitretin or within 3 years of discontinuing therapy.

8) The same effective and uninterrupted contraceptive measures must be taken every time therapy is repeated, however long the intervening period may have been, and must be continued for 3 years afterwards. g. craniofacial defects, cardiac and vascular or CNS malformations, skeletal and thymic defects) and the incidence of spontaneous abortion is increased.

This risk applies especially during treatment with acitretin and 2 months after treatment. For up to 3 years after acitretin discontinuation, the risk is lower (particularly in women who have not consumed alcohol) but cannot be entirely excluded (due to possible formation of etretinate).

Therefore, before instituting Acitretin the treating physician must explain clearly and in detail what precautions must be taken. This should include the risks involved and the possible consequences of pregnancy occurring during Acitretin treatment or in the 3 years following its cessation.

2). Primary contraceptive method can be a combination hormonal contraceptive product or an intrauterine device and it is recommended that a condom or diaphragm (cap) is also used. Low dose progesterone-only products (minipills) are not recommended due to indications of possible interference with their contraceptive effect.

For male patients treated with acitretin, available data, based on the level of maternal exposure from the semen and seminal fluid indicate a minimal, if any, risk of teratogenic effects. 3). 3). 7 Effects on ability to drive […]

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

Acitretin is contraindicated in women of childbearing potential unless all of the following conditions of the Pregnancy Prevention Programme are met: • She has severe forms of psoriasis (erythrodermic psoriasis, local or generalized pustular psoriasis) or severe keratinization disorders (congenital ichthyosis, pityriasis rubra pilaris, Darier’s disease, other disorders of keratinization which may be resistant to other therapies) (see section ”Indications”).

• 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 3 years 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 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.

2 in the SPC). • She has acknowledged that she has understood the hazards and necessary precautions associated with the use of acitretin. 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 3 years after cessation of treatment.

• Negative pregnancy test results have been obtained before, during and periodically with 1-3 monthly intervals for a period of 3 years after stopping treatment. The dates and results of pregnancy tests should be documented. If pregnancy occurs in a woman treated with acitretin, 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 3 years 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. 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 3 years after stopping treatment with acitretin, 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 25mUI/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 acitretin. 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 Women should undergo pregnancy test periodically with 1-3 monthly intervals for a period of 3 years after stopping treatment.

Prescribing and dispensing restrictions For women of childbearing potential, the prescription […]

1. Acitretin is highly teratogenic and must not be used by women who are pregnant. 6). The use of Acitretin is contraindicated in women who are breastfeeding. Acitretin is contraindicated in patients with severe hepatic or renal impairment and in patients with chronic abnormally elevated blood lipid values.

Since both acitretin and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated. 5). An increased risk of hepatitis has been reported following the concomitant use of methotrexate and etretinate.

5). Concomitant administration of Acitretin with other retinoids or Vitamin A is contraindicated due to the risk of hypervitaminosis A. Owing to the presence of glucose, patients with rare glucose-galactose malabsorption should not take this medicine.