Acitretin Capsules USP 22.5mg – Taj Pharma

1. Name of the medicinal product
2. Acitretin Capsules USP 10mg – Taj Pharma
   Acitretin Capsules USP 17.5mg – Taj Pharma
   Acitretin Capsules USP 22.5mg – Taj Pharma
   Acitretin Capsules USP 25mg – Taj Pharma
   2. Qualitative and quantitative composition

   a) Acitretin Capsules USP 10mg – Taj Pharma
   Each hard gelatin capsules contains:
   Acitretin USP 10mg
   Excipients: Q.S.
   b) Acitretin Capsules USP 17.5mg – Taj Pharma
   Each hard gelatin capsules contains:
   Acitretin USP 17.5mg
   Excipients: Q.S.
   c) Acitretin Capsules USP 22.5mg – Taj Pharma
   Each hard gelatin capsules contains:
   Acitretin USP 22.5mg
   Excipients: Q.S.
   d) Acitretin Capsules USP 25mg – Taj Pharma
   Each hard gelatin capsules contains:
   Acitretin USP 25mg
   Excipients:  Q.S.

   Excipient with known affect: Glucose (see section 4.3).

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Hard Gelatin Capsules for oral administration.

4. Clinical particulars
   • Therapeutic indications

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

• Posology and method of administration

Posology

Acitretin Taj Pharma should only be prescribed by physicians who are experienced in the use of systemic retinoids and understand the risk of teratogenicity associated with Acitretin Taj Pharma therapy (see section 4.6).

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 Taj Pharma. 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 Taj Pharma is contraindicated in children unless, in the opinion of the physician, the benefits significantly outweigh the risks.

Acitretin Taj Pharma should be used only when all alternative therapies have proved inadequate. 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.

Combination therapy

Other dermatological therapy, particularly with keratolytics, should normally be stopped before administration of Acitretin Taj Pharma. However, the use of topical corticosteroids or bland emollient ointment may be continued if indicated.

When Acitretin Taj Pharma 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 Taj Pharma.

Method of administration

Acitretin Taj Pharma capsules are for oral administration.

• Contraindications

Hypersensitivity to the active substance, to other retinoids or to any of the excipients listed in section 6.1.

The use of Acitretin Taj Pharma is contraindicated in women who are breastfeeding.

Acitretin Taj Pharma is contraindicated in patients with severe hepatic or renal impairment and in patients with chronic abnormally elevated blood lipid values.

Since both Acitretin Taj Pharma and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated. Supplementary treatment with antibiotics such as tetracyclines is therefore contraindicated (see section 4.5).

An increased risk of hepatitis has been reported following the concomitant use of methotrexate and etretinate. Consequently, the concomitant use of methotrexate and Acitretin Taj Pharma is contraindicated (see section 4.5).

Concomitant administration of Acitretin Taj Pharma 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 for use

Pregnancy Prevention Programme

This medicinal product is TERATOGENIC.

Acitretin Taj Pharma 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. At least one highly effective method of contraception (i.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.
• She understands the need and accepts to undergo regular pregnancy testing before, ideally monthly during treatment and periodically with 1-3 monthly intervals for a period of 3 years after stopping treatment (see section “Fertility, pregnancy and lactation” and 5.2 in the SPC).
• She has acknowledged that she has understood the hazards and necessary precautions associated with the use of Acitretin Taj Pharma.

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.
• The patient understands that she must consistently and correctly use one highly effective method of contraception (i.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 Taj Pharma, 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. If the prescribing physician is not in a position to provide such information the patient should be referred to the relevant healthcare professional

As a minimum requirement, female patients of childbearing potential must use at least one highly effective method of contraception (i.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 Taj Pharma, 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 Taj Pharma.

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 duration of Acitretin Taj Pharma Capsuleshould 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 Acitretin Taj Pharma Capsuleshould occur on the same day.

This monthly follow-up will allow ensuring that regular pregnancy testing and monitoring is performed and that the patient is not pregnant before receiving the next cycle of medication.

Male patients

The available data suggest that the level of maternal exposure from the semen of the patients receiving Acitretin Taj Pharma Capsuleis not of a sufficient magnitude to be associated with the teratogenic effects of Acitretin Taj Pharma Capsule. Male patients should be reminded that they must not share their medication with anyone, particularly not females.

Additional precautions

Patients should be instructed never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of treatment.

Patients should not donate blood during therapy and for 3 years following discontinuation of Acitretin Taj Pharma because of the potential risk to the foetus of a pregnant transfusion recipient.

Educational material

In order to assist prescribers, pharmacists and patients in avoiding foetal exposure to Acitretin Taj Pharma the Marketing Authorisation Holder will provide educational material to reinforce the warnings about the teratogenicity of Acitretin Taj Pharma, to provide advice on contraception before therapy is started and to provide guidance on the need for pregnancy testing.

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

Psychiatric disorders

Depression, depression aggravated, anxiety, and mood alterations have been reported in patients treated with systemic retinoids, including Acitretin Taj Pharma. Particular care should be taken in patients with a history of depression. Patients should be monitored for signs of depression and referred for appropriate treatment if necessary. Awareness by family or friends may be useful to detect mental health deterioration.

Clinical evidence has shown that etretinate can be formed with concurrent ingestion of Acitretin Taj Pharma and alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than Acitretin Taj Pharma.

Women of childbearing age must not consume alcohol (in drinks, food or medicines) during treatment with Acitretin Taj Pharma and for 2 months after cessation of Acitretin Taj Pharma therapy.

Hepatic function should be checked before starting treatment with Acitretin Taj Pharma, 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 Taj Pharma must be withdrawn. In such cases it is advisable to continue monitoring hepatic function for at least 3 months (see section 4.8).

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. Acitretin Taj Pharma treatment should be discontinued in case of uncontrolled levels of hypertriglyceridemia or if symptoms of pancreatitis occur.

Decreased night vision has been reported with Acitretin Taj Pharma 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 Taj Pharma immediately and be referred for neurologic evaluation and care (see section 4.8).

In adults, especially elderly, receiving long-term treatment with Acitretin Taj Pharma, appropriate examinations should be periodically performed in view of possible ossification abnormalities (see section 4.8 ). Any patients complaining of atypical musculo-skeletal symptoms on treatment with Acitretin Taj Pharma should be promptly and fully investigated to exclude possible Acitretin Taj Pharma-induced bone changes. If clinically significant bone or joint changes are found, Acitretin Taj Pharma 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 Taj Pharma. Acitretin Taj Pharma 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 Taj Pharma 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.

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

High risk patient:

In patients with diabetes, alcoholism, obesity, cardiovascular risk factors or a lipid metabolism disorder undergoing treatment with Acitretin Taj Pharma, 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 Taj Pharma 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 Taj Pharma should only be prescribed by physicians who are experienced in the use of systemic retinoids and understand the risk of teratogenicity associated with Acitretin Taj Pharma therapy.

Acitretin Taj Pharma is highly teratogenic. The risk of giving birth to a deformed child is exceptionally high if Acitretin Taj Pharma is taken before or during pregnancy, no matter for how long or at what dosage. Foetal exposure to Acitretin Taj Pharma 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 Taj Pharma 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 Taj Pharma therapy.

Patients should be warned of the possibility of alopecia occurring (see section 4.8 Undesirable effects).

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

Interaction with other medicinal products and other forms of interaction

Concomitant administration of methotrexate, tetracyclines or vitamin A and other retinoids with Acitretin Taj Pharma is contraindicated, see section 4.3. 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 Taj Pharma therapy, see section 4.6. 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 Taj Pharma 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 Taj Pharma and for 2 months after cessation of Acitretin Taj Pharma therapy. (See section 4.4 and 5.2).

In concurrent treatment with phenytoin, it must be remembered that Acitretin Taj Pharma partially reduces the protein binding of phenytoin. The clinical significance of this is as yet unknown.

Interactions between Acitretin Taj Pharma and other substances (e.g. digoxin, cimetidine) have not been observed to date.

Investigations into the effect of Acitretin Taj Pharma on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction.

Fertility, pregnancy and lactation

Women of childbearing potential / Contraception in males and females

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 Taj Pharma, available data, based on the level of maternal exposure from the semen and seminal fluid indicate a minimal, if any, risk of teratogenic effects.

Pregnancy

Acitretin Taj Pharma is contraindicated in pregnant women (see section 4.3).

Breastfeeding

Acitretin Taj Pharma must not be given to nursing mothers (see section 4.3).

Effects on ability to drive and use machines

Decreased night vision has been reported with Acitretin Taj Pharma therapy (see section “Undesirable effects”). 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).

Undesirable effects

Summary of the safety profile

Undesirable effects are seen in most patients receiving Acitretin Taj Pharma. However, the toxic dose of Acitretin Taj Pharma 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.

Undesirable effects reported for Acitretin Taj Pharma in clinical trials or as post-marketing events are listed below by System Organ Class and frequency. The frequencies of adverse events are ranked according to the following:

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)

Not known (cannot be estimated from the available data)

* Dryness of the conjunctivae may lead to mild-to-moderate conjunctivitis or xerophthalmia and result in intolerance of contact lenses; it may be alleviated by lubrication with artificial tears or topical antibiotics.

** Usually noted 4 to 8 weeks after starting therapy, and are reversible following discontinuation of Acitretin Taj Pharma. Full recovery usually occurs within 6 months of stopping treatment in the majority of patients.

Paediatric population

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 Taj Pharma. In children, growth parameters and bone development must be closely monitored.

Other special populations

Diabetics

Retinoids can either improve or worsen glucose tolerance (see section 4.4).

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.

Overdose

Manifestations of acute Vitamin A toxicity include severe headache, vertigo, nausea or vomiting, drowsiness, irritability and pruritus. Signs and symptoms of accidental or deliberate overdosage with Acitretin Taj Pharma would probably be similar. Specific treatment is unnecessary because of the low acute toxicity of the preparation.

Because of the variable absorption of the drug, gastric lavage may be worthwhile within the first few hours after ingestion.

5. Pharmacological properties

Pharmacodynamic properties

Pharmacotherapeutic group: Antipsoriatics, retinoids for treatment of psoriasis

Mechanism of action

Retinol (Vitamin A) is known to be essential for normal epithelial growth and differentiation, though the mode of this effect is not yet established. Both retinol and retinoic acid are capable of reversing hyperkeratotic and metaplastic skin changes. However, these effects are generally only obtained at dosages associated with considerable local or systemic toxicity. Acitretin Taj Pharma, a synthetic aromatic derivative of retinoic acid, has a favourable therapeutic ratio, with a greater and more specific inhibitory effect on psoriasis and disorders of epithelial keratinisation. The usual therapeutic response to Acitretin Taj Pharma consists of desquamation (with or without erythema) followed by more normal re-epithelialisation.

Acitretin Taj Pharma is the main active metabolite of etretinate.

Pharmacokinetic properties

Absorption

Acitretin Taj Pharma reaches peak plasma concentration 1 – 4 hours after ingestion of the drug. Bioavailability of orally administered Acitretin Taj Pharma is enhanced by food. Bioavailability of a single dose is approximately 60%, but inter-patient variability is considerable (36 – 95%).

Distribution

Acitretin Taj Pharma is highly lipophilic and penetrates readily into body tissues. Protein binding of Acitretin Taj Pharma exceeds 99%. In animal studies, Acitretin Taj Pharma passed the placental barrier in quantities sufficient to produce foetal malformations. Due to its lipophilic nature, it can be assumed that Acitretin Taj Pharma passes into breast milk in considerable quantities.

Biotransformation

Acitretin Taj Pharma is metabolised by isomerisation into its 13-cis isomer (cis Acitretin Taj Pharma), by glucuronidation and cleavage of the side chain.

Clinical evidence has shown that etretinate can be formed with concurrent ingestion of Acitretin Taj Pharma and alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than Acitretin Taj Pharma (see section 4.4, 4.5 and 4.6).

Elimination

Multiple-dose studies in patients aged 21 – 70 years showed an elimination half-life of approximately 50 hours for Acitretin Taj Pharma and 60 hours for its main metabolite in plasma, cis Acitretin Taj Pharma, which is also a teratogen. From the longest elimination half-life observed in these patients for Acitretin Taj Pharma (96 hours) and cis Acitretin Taj Pharma (123 hours), and assuming linear kinetics, it can be predicted that more than 99% of the drug is eliminated within 36 days after cessation of long-term therapy. Furthermore, plasma concentrations of Acitretin Taj Pharma and cis Acitretin Taj Pharma dropped below the sensitivity limit of the assay (< 6ng/ml) within 36 days following cessation of treatment. Acitretin Taj Pharma is excreted entirely in the form of its metabolites, in approximately equal parts via the kidneys and the bile.

Preclinical safety data

None stated.

6. Pharmaceutical particulars

List of excipients

Capsule content:

Glucose, liquid, spray-dried, Sodium ascorbate, Gelatin, Purified water, Microcrystalline cellulose

Capsule shell:

Gelatin, Iron oxide black, Iron oxide yellow, Iron oxide red,Titanium dioxide

Printing ink:

Shellac, N-Butyl alcohol, Isopropyl alcohol, Propylene glycol, Ammonium hydroxide, Iron oxide black

Incompatibilities

None

Shelf life

Acitretin Taj Pharma capsules have a shelf-life of 3 years.

Special precautions for storage

Do not store above 25°C. Store in the original package.

Nature and contents of container

PVC/PVDC (Duplex) or PVC/PE/PVDC (Triplex) blisters with aluminium cover foil containing 56 or 60 capsules.

Not all pack sizes may be marketed.

Special precautions for disposal and other handling

None.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Acitretin-Taj Pharma Capsules USP 22.5mg Taj Pharma

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

WARNING

Can seriously harm an unborn baby

Women must use effective contraception

Do not use if you are pregnant or think you may be pregnant

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only.
• Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Acitretin-Taj Pharma is and what it is used for
2. What you need to know before you take Acitretin-Taj Pharma
3. Important information for women
4. How to take Acitretin-Taj Pharma
5. Possible side effects
6. How to store Acitretin-Taj Pharma
7. Contents of the pack and other information
8. What Acitretin-Taj Pharma is and what it is used for

The name of your medicine is Acitretin-Taj Pharma 10mg Capsules or Acitretin-Taj Pharma 25mg Capsules but will be referred to as Acitretin-Taj Pharma throughout this leaflet.

Acitretin-Taj Pharma Capsules contains a medicine called Acitretin-Taj Pharma. This belongs to a group of medicines called ‘retinoids’. Acitretin-Taj Pharma is used to treat severe skin problems where the skin has become thick and maybe scaly. These skin problems include psoriasis, ichthyosis and keratosis follicularis (Darier’s disease). It works by making your skin grow more normally.

Acitretin-Taj Pharma is normally used while under the care of a specialist dermatologist (skin doctor).

2. What you need to know before you take Acitretin-Taj Pharma

Do not take Acitretin-Taj Pharma:

• If you are pregnant or breast-feeding.
• If there is any chance you could become pregnant, you must follow the precautions under “Pregnancy and prevention programme”, see section on

Warnings and precautions

• If you might get pregnant while taking Acitretin-Taj Pharma or within 3 years of stopping it (see Section 3:
• ‘Important information for women’),
• If you are taking an antibiotic called tetracycline (for an infection) or a medicine called methotrexate (for skin problems, arthrisits or cancer). See Section 2: ‘Other medicines and Acitretin-Taj Pharma’,
• If you are taking other retinoid medicines; or medicines, vitamin supplements or foods that contain Vitamin A (see Section 2: ‘Other medicines and Acitretin-Taj Pharma’),
• If you have kidney or liver problems,
• If you have very high levels of fat in your blood (also known as ‘hyperlipidaemia’).

Do not take Acitretin-Taj Pharma Capsules if you are allergic (hypersensitive) to:

• Acitretin-Taj Pharma or any of the other ingredients of this medicine (listed in section 7).
• Other ‘retinoid’ medicines. These include isotretinoin and tazarotene.

Do not take Acitretin-Taj Pharma if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Acitretin-Taj Pharma.

PREGNANCY AND PREVENTION PROGRAMME:

Women who are pregnant must not take Acitretin-Taj Pharma:

This medicine can seriously harm an unborn baby (the medicine is said to be ‘teratogenic’) – it can cause serious abnormalities of the unborn baby’s brain, face, ear, eye, heart and certain glands (thymus gland and parathyroid gland). It also makes a miscarriage more likely. This may happen even if Acitretin-Taj Pharma is taken only for a short time during pregnancy.

• You must not take Acitretin-Taj Pharma if you are pregnant or if you think you might be pregnant.
• You must not take Acitretin-Taj Pharma if you are breastfeeding.
• The medicine is likely to pass into your milk and may harm your baby.
• You must not take Acitretin-Taj Pharma if you could get pregnant during treatment.
• You must not get pregnant for 3 years after stopping this treatment because some medicine may still be left in your body.

Women who could get pregnant are prescribed Acitretin-Taj Pharma under strict rules. This is because of the risk of serious harm to the unborn baby

These are the rules:

• Your doctor must explain the risk of harm to the unborn baby – you must understand why you must not get pregnant and what you need to do to prevent getting pregnant.
• You must have talked about contraception (birth control) with your doctor. The doctor will give you information on how not to get pregnant. The doctor may send you to a specialist for contraception advice.
• Before you start treatment, your doctor will ask you to take a pregnancy test. The test must show that you are not pregnant when starting treatment with Acitretin-Taj Pharma.

Women must use effective contraception before, during and after taking Acitretin-Taj Pharma:

• You must agree to use at least one very reliable method of contraception (for example an intra uterine device or contraceptive implant) or, two effective methods that work in different ways (for example a hormonal contraceptive pill and a condom). Discuss with your doctor which methods would be suitable for you.
• You must use contraception for a month before taking Acitretin-Taj Pharma, during treatment and for 3 years afterwards.
• You must use contraception even if you do not have periods or you are not sexually active (unless your doctor decides this is not necessary).

Women must agree to pregnancy testing before, during and after taking Acitretin-Taj Pharma:

• You must agree to regular follow-up visits, ideally every month.
• You must agree to have regular pregnancy tests, ideally every month during treatment and, because some medicine may still be left in your body, every 1 to 3 months for 3 years after stopping Acitretin-Taj Pharma (unless your doctor decides this is not necessary in your case).
• You must agree to extra pregnancy tests if your doctor asks you.
• You must not get pregnant during treatment or for 3 years afterwards because some medicine may still be left in your body.
• Your doctor will discuss all these points with you, using a checklist and will ask you (or a parent/ guardian) to sign it. This form confirms that you have been told about the risks and that you will follow the rules above.

If you get pregnant while taking Acitretin-Taj Pharma, stop taking the medicine straight away, and contact your doctor. Your doctor may send you to a specialist for advice.

Also, if you become pregnant within 3 years after you stop taking Acitretin-Taj Pharma, you should contact your doctor. Your doctor may send you to a specialist for advice.

Advice for men

The levels of oral retinoid in the semen of men taking Acitretin-Taj Pharma are too low to harm their partners’ unborn baby. However, you must never share your medication with anyone.

Additional precautions

You should never give this medicinal product to another person. Please take any unused Acitretin-Taj Pharma capsules to your pharmacist at the end of treatment.

Warnings and precautions

Talk to your doctor or pharmacist before taking Acitretin-Taj Pharma if:

• You suffer from high levels of sugar in the blood (diabetes). You will need to check your blood sugar levels more often when you start taking Acitretin-Taj Pharma.
• You have high levels of fat in your blood, you are obese, drink a lot of alcohol or at risk of heart problems. Your doctor may need to do blood tests while you are taking Acitretin-Taj Pharma to check the amount of fat and/or sugar in your blood and check your blood pressure.
• You are going out into strong sunlight or you are going to use a sun bed. Acitretin-Taj Pharma can make the effects of UV light on the skin stronger. Before going out into strong sunlight apply a sunblock to exposed skin.
• You have ever had any mental health problems including depression, aggressive tendencies or mood changes. This is because taking Acitretin-Taj Pharma may affect your mood.

A serious condition which causes the small blood vessels (capillaries) to leak has been reported very rarely (Capillary Leak Syndrome/Retinoic Acid Syndrome). This can lead to severe hypotension (low blood pressure), oedema (build-up of fluid leading to swelling) and shock (collapse).

A serious skin reaction with symptoms such as rash, blistering or peeling of the skin (Exfoliative dermatitis) has been reported very rarely.

Acitretin-Taj Pharma may affect your liver function. Your doctormay need to do blood tests whilst you are taking thismedicine to check your liver function.

Acitretin-Taj Pharma may cause increased pressure in the head. You should tell your doctor if you experience severe headaches, feeling or being sick or changes in sight.Your doctor may carry out further checks.

Acitretin-Taj Pharma may cause changes in bone growth. You should tell your doctor if you feel pain in your muscles or bones. Your doctor may carry out further checks.

Mental health problems

You may not notice some changes in your mood and behaviour and so it is very important that you tell your friends and family that this medicine could affect your mood and behaviour. They may notice these changes and help you identify any problems that you need to talk to your doctor about.  Hair loss is a very common side effect of Acitretin-Taj Pharma.

If any of the above apply to you, or if you are not sure, talk to your doctor or pharmacist before you take Acitretin-Taj Pharma.

Children

Acitretin-Taj Pharma should not be given to children. Acitretin-Taj Pharma may cause changes in bone growth in children.

Other medicines and Acitretin-Taj Pharma

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Acitretin-Taj Pharma can affect the way some other medicines work. Also some other medicines can affect the way Acitretin-Taj Pharma works.

Do not take Acitretin-Taj Pharma, and tell your doctor or pharmacist, if you are taking any of the following medicines:

• An antibiotic called tetracycline (for an infection).
• A medicine called methotrexate (for skin problems, arthritis or cancer).
• Low dose progesterone only contraceptives (‘minipills’).
• Medicines or vitamin supplements that contain Vitamin A.
• Other retinoid medicines, such as isotretinoin or tazarotene.
• Tell your doctor or pharmacist if you are taking the following medicine:
• Phenytoin (used to treat epilepsy).

Acitretin-Taj Pharma with food, drink and alcohol

Women of childbearing potential should not consume alcohol (in drinks, food or medicines) during treatment with Acitretin-Taj Pharma and for 2 months after cessation of therapy. Concurrent ingestion of Acitretin-Taj Pharma and alcohol may result in formation of a compound (etretinate), which may be harmful to an unborn child, and if formed takes some time for it to be totally removed from the body.

Driving and using machines

Your vision may be affected, particularly at night time, while you are taking Acitretin-Taj Pharma. Be careful if you are driving or using any tools or machines.

Important information for blood donors

You should not donate blood during treatment with this medicine and for 3 years after stopping Acitretin-Taj Pharma because an unborn baby could be harmed if a pregnant patient receives your blood.

3. Important information for women

Acitretin-Taj Pharma will damage an unborn baby. The following instructions must be strictly followed, even if you have fertility problems:

Pregnancy, breast-feeding and fertility

For more information on pregnancy and contraception, see section 2 “Pregnancy and prevention programme”. Acitretin-Taj Pharma 10mg and 25mg Capsules Acitretin-Taj Pharma

Birth control (contraception) and pregnancy tests

If you are a female patient at an age where you could get pregnant:

• You must use an effective method of birth control (contraception) for at least 1 month before you start taking Acitretin-Taj Pharma, while you are taking it, and for 3 years after you stop taking it.
• Your doctor will want you to have a pregnancy test about 2 weeks before starting treatment, which must be negative. You may also be asked to have regular pregnancy tests while you are taking Acitretin-Taj Pharma.
• Start taking Acitretin-Taj Pharma after the negative pregnancy test, on the second or third day of your next period.
• While you are taking Acitretin-Taj Pharma, and for 3 years after stopping it, contact your doctor straight away if you get pregnant or think you may be pregnant.

If you have any questions about these instructions, talk to your doctor or pharmacist before taking Acitretin-Taj Pharma.

4. How to take Acitretin-Taj Pharma

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

• Take Acitretin-Taj Pharma at a meal time, or with a glass of milk.
• Swallow each capsule whole.

The dose varies from one patient to another. Your doctor will work out the right dose for you.

Adults and elderly people

• The recommended starting dose for adults and elderly people is 25mg or 30mg once a day.
• After 2 to 4 weeks, your doctor may increase or decrease your dose. This will depend on how well it works and how it affects you.
• The maximum dose is 75mg a day.
• Most people take Acitretin-Taj Pharma for up to 3 months. However, your doctor may decide that you need to take it for longer. You must not take Acitretin-Taj Pharma for more than 6 months at a time.

Use in children

Acitretin-Taj Pharma should not be given to children. If it is given to a child, the doctor will decide the correct dose. This is based on the child’s weight.

If you take more Acitretin-Taj Pharma than you should

If you take more Acitretin-Taj Pharma than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you. The following effects may happen: a bad headache, dizziness, feeling or being sick, being sleepy or irritable or having itchy skin.

If you forget to take Acitretin-Taj Pharma

• If you forget to take a dose, take it as soon as you remember. However, if it is nearly time for the next dose, skip the missed dose.
• Do not take a double dose (two doses at the same time) to make up for a forgotten dose.

If you stop taking Acitretin-Taj Pharma

Your doctor can judge best when and how you must stop taking Acitretin-Taj Pharma. Always contact your doctor before you want to stop taking the medicine.

If someone else takes your Acitretin-Taj Pharma Capsules by mistake, they should talk to a doctor or go to a hospital straight away.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

5. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

You will probably have some side effects during treatment with Acitretin-Taj Pharma, even before you see your skin starting to get better. These effects often wear off as your treatment continues. Your doctor can help you to deal with them.

Stop taking Acitretin-Taj Pharma and see a doctor straight away if you experience the following side effects:

• Immediate allergic reaction with symptoms such as skin rash, swelling or itching of the skin, swelling of the face, lips, throat or tongue, red and swollen eyes, severe nasal congestion, asthma or wheezing. The reaction can be minor to life-threatening.
• A severe headache.
• Feeling or being sick.
• Problems with your eye sight.
• You feel any aches and pains in your muscles, bones or joints. This may mean you have extra growth on the surface of your bones. This can happen if you take Acitretin-Taj Pharma for a long time.

Your doctor may want to check you regularly to find out if this is happening. These checks are particularly important if a child is taking Acitretin-Taj Pharma.

Other possible side effects:

Very common (may affect more than 1 in 10 people):

• Dry, irritated or swollen eyes, which may lead to intolerance of contact lenses,
• Dry, irritated or runny nose, nose bleeding,
• Dry mouth, thirst,
• Dryness or inflammation of the lips, which may be alleviated by application of a fatty ointment. Itching, hair loss, peeling of the skin from the palms of hands or the soles of the feet or even rest of the body,
• Changes in how the liver is working (shown by blood test),
• Increased levels of fats in your blood (shown by blood test).

Common (may affect up to 1 in 10 people):

• Headache,
• Inflammation of the mucous tissue of the mouth, abdominal pain, diarrhoea, feeling sick, being sick,
• Fragile skin, sticky feeling on the skin or a rash, skin inflammation, changes to the texture of the hair, brittle nails, skin infection around a nail, redness of the skin,
• Joint pain, muscle pain,
• Swelling of hands, ankles and feet.

Uncommon (may affect up to 1 in 100 people):

• Dizziness,
• blurred vision,
• Inflammation of the gums,
• Inflammation of the liver,
• Fissures, cracks or fine linear scars in the skin e.g. around the mouth (rhagades), blisters and inflammation of the skin (dermatitis bullous), skin being more sensitive to the sun (photosensitivity reaction).

Rare (may affect up to 1 in 1,000 people):

• Damage to the peripheral nervous system, which may include symptoms like muscle weakness, numbness and tingling in the feet and hands or burning, stabbing or shooting pain.

Very rare (may affect up to 1 in 10,000 people):

• increased blood pressure in the skull,
• Night blindness, inflammation of the cornea in the eye (ulcerative keratitis),
• yellowing of the skin or the whites of the eyes (jaundice),
• Bone pain, changes in bone growth.

Side effects with unknown frequency:

• Infection of the vagina (also known as candida or thrush),
• Impaired hearing, ringing in the ear (tinnitus),
• A serious condition which causes the small blood vessels (capillaries) to leak (Capillary Leak Syndrome/Retinoic Acid Syndrome). This can lead to severe hypotension (low blood pressure), oedema (build-up of fluid leading to swelling) and shock (collapse),
• flushing; sweating, skin redness on the face,
• Changes in the way things taste; bleeding in the rectum,
• a serious skin reaction with symptoms such as rash, blistering or peeling of the skin (Exfoliative dermatitis),
• Small, reddish bumps or nodules on the skin that may bleed easily (pyogenic granuloma), scaling or thinning of the skin,
• Cracks or scaring at the corners of the mouth,
• Loss of eyelashes or eyebrows (madarosis),
• Improved or worsened glucose tolerance in diabetic patients,
• General unwell feeling, drowsiness,
• swelling of the face, lips, throat or tongue (angioedema),
• Severe itchy skin rash with pale or red irregular raised patches (hives),
• Changes in the sound of the voice (dysphonia).

An initial worsening of psoriasis symptoms is sometimes seen at the beginning of the treatment period.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects, you can help provide more information on the safety of this medicine.

6. How to store Acitretin-Taj Pharma

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after ‘EXP’. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

7. Contents of the pack and other information

What Acitretin-Taj Pharma Capsules contain

The active substance is Acitretin Taj Pharma.

Acitretin Taj Pharma Capsules USP 10mg – Taj Pharma

Acitretin Capsules USP 17.5mg – Taj Pharma

Acitretin Capsules USP 22.5mg – Taj Pharma

Acitretin Capsules USP 25mg – Taj Pharma

The other ingredients are:

• Capsule filling containing disodium edetate, maltodextrin, cellulose microcrystalline, poloxamer 407, purified water and sodium ascorbate.
• Capsule shell containing gelatin, titanium dioxide, iron oxide yellow, iron oxide black and iron oxide red.
• Printing Ink – White containing shellac, titanium dioxide, isopropyl alcohol, N-butyl alcohol and propylene glycol.

What Acitretin -Taj Pharma Capsules and contents of the pack

The capsules are packaged in aluminium blister packs.

Pack sizes: 10, 20, 28, 30, 56, 60, 100, 120 and 500 hard gelatin capsules.

Not all pack sizes may be marketed.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com