Emend 80mg and 125mg CAPSULES and COMBIPACK

EMEND in combination with other anti-emetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of:

• highly emetogenic cancer chemotherapy (see u201cDOSAGE AND DIRECTIONS FOR USEu201d).
• moderately emetogenic cancer chemotherapy (see u201cDOSAGE AND DIRECTIONS FOR USEu201d).

EMEND is given for 3 days as part of a regimen that includes a corticosteroid for 4 days and a 5-HT3 antagonist on day one. The package insert for the co-administered 5-HT3 antagonist must be consulted prior to initiation of treatment with EMEND. The recommended dose of EMEND is 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80 mg once daily in the morning on Days 2 and 3.

Recommended dosing for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy:

**Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. The dose of dexamethasone was chosen to account for drug interactions.

Recommended dosing for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy:

**Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1. The dose of dexamethasone accounts for interactions. See u201cINTERACTIONSu201d for additional information on the administration of EMEND with corticosteroids. Refer to the full prescribing information for co-administered anti-emetic agents. EMEND may be taken with or without food. No dosage adjustment is necessary based on age, gender, race or Body Mass Index (BMI). No dosage adjustment is necessary for patients with severe renal insufficiency (creatinine clearance 9).

EMEND is contraindicated in patients who are hypersensitive to any component of the product. EMEND should not be used concurrently with pimozide, astemizole or cisapride. Inhibition of cytochrome P450 isoenzyme 3A4 (CYP3A4) by aprepitant could result in elevated plasma concentrations of these agents, potentially causing serious or life-threatening reactions, (see u201cINTERACTIONSu201d).

Paediatric use: Safety and effectiveness in paediatric patients have not been established.

EMEND should be used with caution in patients receiving concomitant medicinal products that are primarily metabolised through CYP3A4; some chemotherapy agents are metabolised by CYP3A4 (see u201cINTERACTIONSu201d). Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these concomitant medicinal products (see u201cINTERACTIONSu201d). Consequently, concomitant administration of EMEND with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) should be approached with caution. Co-administration of EMEND with warfarin may result in a clinically significant decrease in International Normalised Ratio (INR) or prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2 week period, particularly at 7 to 10 days following initiation of the 3-day regimen of EMEND with each chemotherapy cycle (see u201cINTERACTIONSu201d). The efficacy of hormonal contraceptives during and for 28 days after administration of EMEND may be reduced. Alternative or back-up methods of contraception should be used during treatment with EMEND and for 1 month following the last dose of EMEND.

Contains sucrose. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take EMEND. Contains sucrose which may have an effect on the glycaemic control of patients with diabetes mellitus.

Severe hepatic insufficiency (Child-Pugh score > 9): There are no clinical or pharmacokinetic data in patients with severe hepatic insufficiency. Caution should be exercised when EMEND is administered in these patients.

Use in the elderly: In clinical studies, the efficacy and safety of EMEND in the elderly (65 years and older) were comparable to those seen in younger patients (younger than 65 years). No dosage adjustment is necessary in elderly patients.

EMEND may have minor influence on the ability to drive and use machines. Dizziness and fatigue may occur following administration of EMEND (see u201cSIDE EFFECTSu201d).

The overall safety of EMEND was evaluated in approximately 6 500 individuals. The most common aprepitant-related adverse experiences reported in patients treated with the aprepitant regimen and greater than the comparator therapy were: Hiccups (4,6 %), increased ALT (2,8 %), dyspepsia (2,6 %), constipation (2,4 %), headache (2,0 %) and decreased appetite (2,0 %).

In 2 clinical trials in patients receiving moderately emetogenic cancer chemotherapy (MEC) EMEND was given in combination with ondansetron and dexamethasone (aprepitant regimen). In Cycle 1, aprepitant-related adverse experiences were reported in approximately 14 % of patients treated with the EMEND regimen. EMEND was discontinued due to aprepitant-related adverse experiences in 0,7 % of patients treated with the EMEND regimen. The most common aprepitant-related adverse experience reported at a greater incidence with the EMEND regimen than with standard therapy was fatigue (1,4 %).

Post-Marketing Experience: The following adverse reactions have been identified during post-marketing use of EMEND. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to the medicine: Skin and subcutaneous tissue disorders: Pruritus, rash, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis. Immune system disorders: Hypersensitivity reactions including anaphylactic reactions.

No specific information is available on the treatment of overdosage with EMEND. Drowsiness and headache were reported in one patient who ingested 1 440 mg of EMEND. In the event of overdose, EMEND should be discontinued and general supportive treatment and monitoring should be provided. EMEND cannot be removed by haemodialysis.