APREPITANT ZENTIVA

Posology Adults Aprepitant is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. The recommended dose is 125mg orally once daily one hour before start of chemotherapy on Day 1 and 80 mg orally once daily on Days 2 and 3 in the morning.

The following regimens are recommended in adults for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy: Highly Emetogenic Chemotherapy Regimen Day 1 Day 2 Day 3 Day 4 Aprepitant 125mg orally 80mg orally 80mg orally none Dexamethasone 12mg orally 8mg orally 8mg orally 8mg orally 5-HT3 antagonists Standard dose of 5-HT3 antagonists.

See the product information for selected 5-HT3 antagonist for appropriate dosing information None None None Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Day 2 to 4. The dose of dexamethasone accounts for active substance interactions.

Moderately Emetogenic Chemotherapy Regimen Day 1 Day 2 Day 3 Aprepitant 125mg orally 80mg orally 80mg orally Dexamethasone 12mg orally None None 5-HT3 antagonists Standard dose of 5-HT3 antagonists. See the product information for selected 5-HT3 antagonist for appropriate None None dosing information Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1.

The dose of dexamethasone accounts for active substance interactions. Paediatric population Adolescents (aged 12 through 17 years) Aprepitant is given for 3 days as part of a regimen that includes a 5-HT3 antagonist. The recommended dose of capsules of aprepitant is 125mg orally on Days 1 and 80 mg orally on Days 2 and 3.

Aprepitant is administered orally 1 hours prior to chemotherapy on Days 1, 2 and 3. If no chemotherapy is given on Days 2 and 3, aprepitant should be administered in the morning. See the Summary of Product Characteristics (SmPC) for the selected 5-HT3 antagonist for appropriate dosing information.

1). The safety and efficacy of the 80 mg and 125mg capsules have not been demonstrated in children less than 12 years of age. No data are available. General Efficacy data in combination with other corticosteroids and 5-HT3 antagonists are limited.

5. Please refer to the SmPC of co-administered 5-HT3 antagonist medicinal products. 2). 2). 2). Hepatic impairment No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment.

Summary of the safety profile The safety profile of aprepitant was evaluated in approximately 6,500 adults in more than 50 studies and 184 children and adolescents in 2 pivotal paediatric clinical trials. 5 %). 9 %). 0 %). Tabulated list of adverse reactions The following adverse reactions were observed in a pooled analysis of the HEC and MEC studies at a greater incidence with aprepitant than with standard therapy in adults or paediatric patients or in post-marketing use.

The frequency categories given in the table are based on the studies in adults; the observed frequencies in the paediatric studies were similar or lower, unless shown in the table. Some less common ADRs in the adult population were not observed in the paediatric studies.

Frequencies 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) and very rare (< 1/10,000), not known (cannot be estimated from the available data). System organ class Adverse reaction Frequency Infection and infestations Candidiasis, staphylococcal infection Rare Blood and lymphatic system disorders Febrile neutropenia, anaemia Uncommon Immune system disorders Hypersensitivity reactions including anaphylactic reactions Not known Decreased appetite CommonMetabolism and nutrition disorders Polydipsia Rare Anxiety UncommonPsychiatric disorders Disorientation, euphoric mood Rare Headache CommonNervous system disorders Dizziness, somnolence Uncommon Cognitive disorder, lethargy, dysgeusia Rare Eye disorders Conjunctivitis Rare Ear and labyrinth disorders Tinnitus Rare Palpitations UncommonCardiac disorders Bradycardia, cardiovascular disorder Rare Vascular disorders Hot flushes/flushing Uncommon Hiccups CommonRespiratory, thoracic and mediastinal disorders Oropharyngeal pain, sneezing, cough, postnasal drip, throat irritation Rare Constipation, dyspepsia Common Eructation, nausea†, vomiting†, gastroesophageal reflux disease, abdominal pain, dry mouth, flatulence Uncommon Gastrointestinal disorders Duodenal ulcer perforation, stomatitis, abdominal distention, faeces hard, neutropenic colitis Rare Rash, acne Uncommon Photosensitivity reaction, hyperhidrosis, seborrhoea, skin lesion, rash prutitic, Stevens-Johnson syndrome/toxic epidermal necrolysis Rare Skin and subcutaneous tissue disorders Pruritus, urticarial Not known Musculoskeletal and connective tissue disorders Muscular weakness, muscle spasms Rare Renal and urinary disorders Dysuria Pollakiuria Uncommon Rare Fatigue Common Asthenia, malaise Uncommon General disorders and administration site conditions Oedema, chest discomfort, gait disturbance Rare ALT increase Common AST increase, blood alkaline phosphatase increased Uncommon Investigations Red blood cells urine positive, blood sodium decreased, weight decreased, neutrophil count decreased, glucose urine present, urine output increased Rare †Nausea and vomiting were efficacy parameters in the first 5 days of post- chemotherapy treatment and were reported as adverse reactions only thereafter.

Patients with moderate to severe hepatic impairment There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. 2). 5). Additionally, concomitant administration with irinotecan should be approached with particular caution as the combination might result in increased toxicity.

5). Co-administration with hormonal contraceptives The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of aprepitant. 5). Excipients Aprepitant capsules contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

Aprepitant capsules contain sodium. This medicinal product contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

1. 5).