Apremilast Glenmark Tablet

Psoriatic arthritis: APREMILAST GLENMARK , alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs) is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.

Psoriasis: APREMILAST GLENMARK , is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to or who have a contraindication to or are intolerant to other systemic therapy, including ciclosporin, methotrexate or psoralen and ultraviolet A light (PUVA).

Posology: The recommended initial dosage titration of APREMILAST GLENMARK from Day 1 to Day 5 is shown in Table 1. Following the 5-day titration, the recommended maintenance dosage is 30 mg twice daily taken orally starting on Day 6. No re-titration is required after initial titration. This titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.

Table 1: Dosage Titration Schedule

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 & thereafter

AM AM PM AM PM AM PM AM PM AM PM

10 mg 10 mg 10 mg 10 mg 20 mg 20 mg 20 mg 20 mg 30 mg 30 mg 30 mg

Special populations

Elderly patients: No dose adjustment is required for this patient population (see sections 4.8 and 5.2).

Dosage Adjustment in Patients with Renal Impairment: No dose adjustment is needed in patients with mild and moderate renal impairment. APREMILAST GLENMARK dosage should be reduced to 30 mg once daily in patients with severe renal impairment (creatinine clearance (CLcr) of less than 30 mL per minute estimated by the Cockcroft u2013 Gault equation). For initial dosage titration in this group, it is recommended that APREMILAST GLENMARK be titrated using only the AM schedule listed in Table 1 and the PM doses be skipped (see Section 5.2 ).

Patients with hepatic impairment: No dose adjustment is necessary for patients with hepatic impairment (see section 5.2 ). The safety of APREMILAST GLENMARK was not evaluated in PsA or psoriasis in patients with hepatic impairment.

Paediatric population: The safety and efficacy of apremilast, as contained in APREMILAST GLENMARK , in children < 18 years have not been established.

Method of administration: APREMILAST GLENMARK is for oral use and can be administered without regard to meals. Do not crush, split, or chew the tablets.

• Patients with a known hypersensitivity to apremilast or to any of the excipients in the APREMILAST GLENMARK formulation (see section 6.1 ).
• Pregnancy (see section 4.6 ).

Psychiatric disorders

Treatment with APREMILAST GLENMARK is associated with an increase in occurrences of depression. APREMILAST GLENMARK is also associated with an increased risk of other psychiatric disorders such as insomnia. Instances of suicidal ideation and behaviour, including suicide, have been observed in patients with or without history of depression (see section 4.8 ). The risks and benefits of starting or continuing treatment with APREMILAST GLENMARK should be carefully assessed if patients report previous or existing psychiatric symptoms or if concomitant treatment with other medicinal products likely to cause psychiatric events is intended. Patients and caregivers should be instructed to notify the prescriber of any changes in behaviour or mood and of any suicidal ideation. If patients suffered from new or worsening psychiatric symptoms, or suicidal ideation or suicidal attempt is identified, it is recommended to discontinue treatment with apremilast.

Diarrhoea, Nausea, and Vomiting

There have been post-marketing reports of severe diarrhoea, nausea, and vomiting associated with the use of APREMILAST GLENMARK . Most events occurred within the first few weeks of treatment. In some cases, patients were hospitalised. Patients aged 65 years or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhoea, nausea, or vomiting. Monitor patients who are more susceptible to complications of diarrhoea or vomiting. Patients who reduced dosage or discontinued APREMILAST GLENMARK generally improved quickly. Consider APREMILAST GLENMARK dose reduction or discontinuation if patients develop severe diarrhoea, nausea, or vomiting.

Severe renal impairment

APREMILAST GLENMARK should be dose reduced to 30 mg once daily in patients with severe renal impairment (see sections 4.2 and 5.2 ).

Underweight patients

Patients who are underweight at the start of treatment should have their body weight monitored regularly. In the event of unexplained and clinically significant weight loss, these patients should be evaluated by a medical practitioner and discontinuation of treatment should be considered.

Excipients:

APREMILAST GLENMARK contains lactose. Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Co-administration of strong cytochrome P450 3A4 (CYP3A4) enzyme inducer, rifampicin, resulted in a reduction of systemic exposure of apremilast, which may result in a loss of efficacy of apremilast. Therefore, the use of strong CYP3A4 enzyme inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin and St. John's Wort) with APREMILAST GLENMARK is not recommended. Co- administration of apremilast with multiple doses of rifampicin resulted in a decrease in apremilast area- under-the-concentration time curve (AUC) and maximum serum concentration (C max ) by approximately 72 % and 43 %, respectively. Apremilast exposure is decreased when administered concomitantly with strong inducers of CYP3A4 (e.g. rifampicin) and may result in reduced clinical response.

In clinical studies, apremilast has been administered concomitantly with topical therapy (including corticosteroids, coal tar shampoo and salicylic acid scalp preparations) and UVB phototherapy. There was no clinically meaningful interaction between ketoconazole and apremilast. APREMILAST GLENMARK can be co-administered with a potent CYP3A4 inhibitor such as ketoconazole. There was no pharmacokinetic interaction between apremilast and methotrexate in psoriatic arthritis patients. APREMILAST GLENMARK can be co-administered with methotrexate. There was no pharmacokinetic interaction between apremilast and oral contraceptives containing ethinyl estradiol and norgestimate. APREMILAST GLENMARK can be co-administered with oral contraceptives.

Women of childbearing potential

Pregnancy should be excluded before treatment can be initiated. Women of childbearing potential should use an effective method of contraception to prevent pregnancy during treatment.

Pregnancy

APREMILAST GLENMARK is contraindicated in pregnancy (see section 4.3 ).

Breast-feeding

It is not known whether apremilast or its metabolites are present in human milk. Mothers taking APREMILAST GLENMARK should not breastfeed their infants (see section 4.3 ).

Fertility

No fertility data is available in humans.

Fatigue has been reported with apremilast, as contained in APREMILAST GLENMARK . Patients should be advised not to drive or use machines until they know how APREMILAST GLENMARK affects their ability to do so.

The most frequently reported adverse reactions apremilast clinical trails were gastrointestinal (GI) disorders including diarrhoea nausea and vomiting. Other frequently reported adverse reactions included upper respiratory tract infections, headache, and tension headache and back pain.

Tabulated summary of adverse reactions

The adverse reactions observed in patients treated with apremilast are listed below by system organ class (SOC) and frequency for all adverse reactions. Within each SOC and frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Summary of adverse reactions in psoriatic arthritis (PsA) and/or psoriasis (PSOR)

System Organ Class Frequency Adverse reaction

Infections and infestations Frequent Bronchitis, upper respiratory tract infection, nasopharangitis*

Immune system disorders Less frequent Hypersensitivity

Metabolism and nutrition disorders Frequent Decreased appetite

Psychiatric disorders Frequent Insomnia, depression

Less frequent Suicidal ideation and behaviour

Nervous system disorders Frequent Migraine*, tension headache*, headache*

Respiratory, thoracic, and mediastinal disorders Frequent Cough

Gastrointestinal disorders Frequent Diarrhoea*, nausea*, vomiting*, dyspepsia, frequent bowel movements, upper abdominal pain*, gastroesophageal reflux disease

Less frequent Gastrointestinal haemorrhage

Skin and subcutaneous tissue disorders Less frequent Rash, urticaria

Frequency unknown angioedema

Musculoskeletal and connective tissue disorders Frequent Back pain*

General disorders and administration site conditions Frequent Fatigue

Investigations Less frequent Weight decrease

* At least one of these adverse reactions was reported as serious.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c 6.04 Adverse Drug Reactions Reporting Form u201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

In overdose, side effects can be precipitated and/or be of increased severity. Patients should be managed by symptomatic and supportive care should there be an overdose.