ACITRETIN CAPSULES

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GENERIC NAME

ACITRETIN

STRENGTH

10mg & 25mg

DOSAGE FORM

CAPSULES

What Acitretin is and what it is used for.

Acitretin belongs to a group of medicines called “retinoids”. Acitretin is used to treat severe skin problems where the skin has become thick and possibly scaly. These skin problems include psoriasis, ichthyosis and keratosis follicularis (Darier’s disease). It works by making your skin grow more normally. Patients using acitretin, have to be under the care of a specialist dermatologist.

What you need to know before you take Acetylcysteine Injection.

Warnings and precautions

Talk to your doctor or nurse before using Acitretin Capsules if:

  • you are pregnant or thinking you may be pregnant or you are breast-feeding.
  • you have liver or kidney problems.
  • you have high cholesterol levels.
  • you are taking an antibiotic called tetracycline or a medicine called methotrexate. 
  • you are taking other retinoid medicines  or medicines, vitamin supplements or foods containing vitamin A.
  • you have diabetes as you would have to check your glucose levels more often whilst taking acitretin.
  • you have Capillary Leak Syndrome.

If you have any doubts about whether this medicine should be given to you, discuss things more fully with the doctor or nurse.

Other medicines and Acitretin Capsules

Concomitant administration of methotrexate, tetracyclines or vitamin A and other retinoids with acitretin is contraindicated. An increased risk of hepatitis has been reported following the concomitant use of methotrexate and etretinate.

Low dose progesterone-only products (minipills) may be an inadequate method of contraception during acitretin therapy. 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. 

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.

Interactions between Acitretin and other substances (e.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.

Pregnancy, breast-feeding and fertility

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.

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.

 Driving and using machines

Decreased night vision has been reported with Acitretin therapy. Patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night. Visual problems should be carefully monitored

How to take Acitretin Capsules

Acitretin should only be prescribed by physicians or specialist dermatologists who are experienced in the use of systemic retinoids and understand the risk of teratogenicity associated with acitretin therapy.

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-effect 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. 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.

Children:

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.

The dosage should be established according to bodyweight. The daily dosage is about 0.5mg/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.

Possible side effects

Undesirable effects are seen in most patients receiving acitretin. However, the toxic dose of Acitretin is close to the therapeutic dose and most patients experience some side-effects during the initial period whilst dosage is being adjusted. They are usually reversible with reduction of dosage or discontinuation of therapy.

The skin and mucous membranes are most commonly affected, and it is recommended that patients should be so advised before treatment is commenced. An initial worsening of psoriasis symptoms is sometimes seen at the beginning of the treatment period.

The most frequent undesirable effects observed are symptoms of hypervitaminosis A, e.g. dryness of the lips, which can be alleviated by application of a fatty ointment.

Therapeutic indications

For the treatmentment of:

  • Severe extensive psoriasis which is resistant to other forms of therapy.
  • Palmo-plantar pustular psoriasis.
  • Severe congenital ichthyosis.
  • Severe Darier’s disease (keratosis follicularis).

Method of administration

The capsules should be taken orally once daily with meals or with milk.

Contraindications

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. Supplementary treatment with antibiotics such as tetracyclines is therefore contraindicated.

An increased risk of hepatitis has been reported following the concomitant use of methotrexate and etretinate. Consequently, the concomitant use of methotrexate and Acitretin is contraindicated.

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.

Special warnings and precautions

Full patient information about the teratogenic risk and the strict pregnancy prevention measures should be given by the physician to all patients, both male and female.

Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than acitretin. Women of childbearing age must not consume alcohol (in drinks, food or medicines) during treatment with acitretin and for 2 months after cessation of acitretin therapy. Contraceptive measures and pregnancy tests must also be taken for 3 years after completion of acitretin treatment.

Women of childbearing potential must not receive blood from patients being treated with acitretin. Therefore donation of blood by a patient being treated with acitretin is prohibited during and for three years after completion of treatment with acitretin.

Due to the risk of foetal malformations, the medicine must not be passed on to other people. Unused or expired products should be returned to a pharmacy for disposal.

Hepatic function should be checked before starting treatment with Acitretin, every 1 – 2 weeks for the first 2 months after commencement and then every 3 months during treatment. If abnormal results are obtained, weekly checks should be instituted. If hepatic function fails to return to normal or deteriorates further, Acitretin must be withdrawn. In such cases it is advisable to continue monitoring hepatic function for at least 3 months.

Serum cholesterol and serum triglycerides (fasting values) must be monitored before starting treatment, one month after the commencement and then every 3 months during treatment.

Decreased night vision has been reported with acitretin therapy. Patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night. Visual problems should be carefully monitored (see section 4.8).

There have been rare reports of benign intracranial hypertension. Patients with severe headache, nausea, vomiting, and visual disturbances should discontinue acitretin immediately and be referred for neurologic evaluation and care.

In adults, especially elderly, receiving long-term treatment with Acitretin, appropriate examinations should be periodically performed in view of possible ossification abnormalities. Any patients complaining of atypical musculo-skeletal symptoms on treatment with Acitretin should be promptly and fully investigated to exclude possible acitretin-induced bone changes. If clinically significant bone or joint changes are found, Acitretin therapy should be discontinued.

Paediatric population

Since there have been occasional reports of bone changes in children, including premature epiphyseal closure, skeletal hyperostosis and extraosseous calcification after long-term treatment with etretinate, these effects may be expected with acitretin. Acitretin therapy in children is not, therefore, recommended. If, in exceptional circumstances, such therapy is undertaken the child should be carefully monitored for any abnormalities of musculo-skeletal development and growth parameters and bone development must be closely monitored.

It should be emphasized that, at the present time, not all the consequences of life-long administration of acitretin are known.

The effects of UV light are enhanced by retinoid therapy, therefore patients should avoid excessive exposure to sunlight and the unsupervised use of sun lamps. Where necessary a sun-protection product with a high protection factor of at least SPF 15 should be used.

High risk patient:

In patients with diabetes, alcoholism, obesity, cardiovascular risk factors or a lipid metabolism disorder undergoing treatment with acitretin, more frequent checks are necessary of serum values for lipids,and/or glycaemia and other cardiovascular risk indicators, e.g. blood pressure. In diabetics, retinoids can either improve or worsen glucose tolerance. Blood-sugar levels must therefore be checked more frequently than usual in the early stages of treatment.

For all high risk patients where cardiovascular risk indicators fail to return to normal or deteriorate further, dose reduction or withdrawal of acitretin should be considered.

In diabetic patients, retinoids can alter glucose tolerance. Blood sugar levels should therefore be checked more frequently than usual at the beginning of the treatment period.

Very rare cases of Capillary Leak Syndrome/retinoic acid syndrome have been reported from world-wide post marketing experience.

Very rare cases of Exfoliative dermatitis have been reported from world-wide post marketing experience.

Acitretin should only be prescribed by physicians who are experienced in the use of systemic retinoids and understand the risk of teratogenicity associated with acitretin therapy.

Acitretin is highly teratogenic. 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. Foetal exposure to Acitretin always involves a risk of congenital malformation.

Primary contraceptive method is 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.

Acitretin has been shown to affect diaphyseal and spongy bone adversely in animals at high doses in excess of those recommended for use in man. Since skeletal hyperostosis and extraosseous calcification have been reported following long-term treatment with etretinate in man, this effect should be expected with acitretin therapy.

Patients should be warned of the possibility of alopecia occurring.

Treatment with high dose retinoids can cause mood changes including irritability, aggression and depression.

Possible side effects

Possible side effects of Acitretin occur in varying degrees from patient to patient. Most of the side effects are dose-related and usually reversible with reduction of dosage or discontinuation of therapy.

At the start of treatment with Acitretin there may be a transient worsening of the psoriasis symptoms.

The skin and mucous membranes are most commonly affected, and it is recommended that patients should be so advised before treatment is commenced.

Very common

  • Over 80% of patients experienced: hypervitaminosis A as e.g. dry lips and possibly inflamed lips (using moisturisers or ’emollients’ from the start of treatment can help to relieve dry skin problems.)
  • 40 – 80% of patients experienced: dry mucous membranes of mouth and nose, peeling of skin, especially the palms of the hands and soles of the feet, rhinitis.
  • 10 – 40% of patients experienced: nose bleed, scaling and thinning of healthy skin with increased sensitivity, erythema, pruritus, sensation of “burning skin”, sensation of “sticky skin”, dermatitis, hair loss, inflammation of the nail wall, nail fragility.

Common

Up to 10% of patients experienced: development of rhagades, inflammation of oral mucosa and gingiva associated with taste disturbances, blistering of the skin, change in pigmentation of the skin and hair, change in growth rate of hair, change in hair structure.

Marked dose dependence has been observed especially with regard to

  • dry skin and mucous membranes, especially of the lips and nose,
  • increased sensitivity of the skin and mucous membranes and
  • hair loss.

Side effects of the skin and mucous membranes occur rather soon (a few days) after start of treatment, hair loss cannot be expected until several weeks into the treatment.

These side effects are reversible after altering the dose or discontinuation of treatment. However, new growth of hair will take some months, due to the hair growth cycle.