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Drug Monographs
Treatment Regimens

Scientific Name:
APREPITANT
Brand Name(s):
Emend®

Drug Monograph

Pharmacology

Mechanism of Action

Selective neurokinin-1 receptor (NK-1) antagonist, acting at central NK-1 receptors.

Pharmacokinetics

Oral Absorption:
well absorbed; bioavailability: 60% to 65%
Cmax at about 4 hours, not affected by food
Distribution:
Excretion in breast-milk unknown
Cross blood brain barrier?Yes
Vd: 70 L
PPB: >95%
Metabolism:
Extensively metabolized by CYP3A4 (minor routes by CYP1A2 & CYP2C19); oxidation at morpholine ring & side chains. Some metabolites with weak activity
Elimination:
Eliminated primarily by metabolism, not renal excretion
Urine: 57%, mostly as metabolites, ~45% in the feces.
Cl: 62-90 mL/min
t½ Elimination: 9-13 hours

Side Effects

EARLY ONSET (days to weeks)
   constipation (10%), diarrhea (10%), dehydration 6%, dizziness 7%, fever 3%
   fatigue (18%), anorexia (10%), headache ( 8.5%)
   nausea (13%), vomiting ( 7.5%)

Therapeutics

Approved Indications

Prevention of acute and delayed nausea & vomiting from highly emetogenic chemotherapy.

Routes

Oral

Dosing

• Take 125mg by mouth before chemotherapy (on Day 1) and 80mg by mouth ond Days 2 & 3
• May be given with a serotonin3 receptor antagonist and steroid on Day 1 and with a steroid on Days 2 & 3 (steroid alone on Day 4)
• Reduce dexamethasone pre-chemotherapy to 12mg, and 8 mg on Days 2-4

Contraindications

• Sensitivity to any component of the product • Moderate cytochrome P-450 3A4 enzyme inhibitor, should not be used concurrently with any CYP3A4 substrate (eg, pimozide, terfenadine, astemizole, or cisapride) which could be elevated in the plasma and which could thereby cause potentially life-threatening reactions.

Monitoring

Clinical Monitoring

RECOMMENDED CRITERIA
NO RECOMMENDED TOXICITY RATINGS

SUGGESTED CRITERIA
NO ADDITIONAL TOXICITY RATINGS

Significant Interactions

Aprepitant is a moderate cytochrome P-450 3A4 enzyme inhibitor, should be used with caution when given concurrently with any CYP3A4 substrates, such as: Chemotherapy agents (e.g. docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine), pimozide, terfenadine, astemizole, or cisapride, warfarin, tolbutamide, oral contraceptives, corticosteroids (reduce dose for equivalent effect). Apprepitant is also a CYP3A4 enzyme substrate, should be used with caution when given concurrently with any strong CYP3A4 inducer (e.g. rifampin, carbamazepine, phenytoin), or strong CYP3A4 inhibitor (e.g. ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir, diltiazem).

Product Information

Commercial Product Description

Brand Name: Emend® White capsules with 80mg, white/pink capsules with 125mg For parenteral formulation, see FOSAPREPITANT

Note

GUIDELINES:

Prevention of Chemotherapy-Induced Nausea and Vomiting:
In combination with a 5-HT3 antagonist and dexamethasone in adult cancer patients treated with chemotherapy that includes cisplatin as a  single day therapy greater than or equal to 70mg/m2 to prevent acute and delayed nausea and vomiting.  Aprepitant may be considered as an option at the onset of cisplatin-based therapy (≥70mg/m2) and commence with the first cycle of this HEC.  In any one patient, the following criteria include:
• Aprepitant will only be used with single day cisplatin-based therapy ≥ 70mg/m2 (and not multiple day cisplatin chemotherapy).
• Aprepitant will not be used in patients receiving moderately emetogenic cancer chemotherapy or radiotherapy.
• The 5-HT3 antagonist should only be used on the first day of cisplatin therapy with aprepitant continuing on Day 2 and Day 3.
• The dose of dexamethasone may be adjusted due to the increased levels of dexamethasone when combined with aprepitant

Availability & Funding

Administrative Information (Nova Scotia)

• CCNS Provincial Formulary Status- Intermediate Level and Take Home Prescription • Go to "Additional Information" tab (above) for links to Provincial Formulary of Cancer Drugs • CDHA Formulary Status- Non-Formulary • Pharmacare Formulary Status- Formulary (Restricted)

New Cancer Drug Fund Status (Nova Scotia)

Pharmacare funding approved for: • Prevention of nausea and vomiting with highly emetogenic chemotherapy In combination with a 5-HT3 antagonist and dexamethasone in adult cancer patients treated with chemotherapy that includes cisplatin as a single day therapy greater than or equal to 70mg/m2 to prevent acute and delayed nausea and vomiting. Aprepitant may be considered as an option at the onset of cisplatin-based therapy (≥70mg/m2) and commence with the first cycle of this HEC. In any one patient, the following criteria include: i. Aprepitant will only be used with single day cisplatin-based therapy ≥ 70mg/m2 (and not multiple day cisplatin chemotherapy). ii. Aprepitant will not be used in patients receiving moderately emetogenic cancer chemotherapy or radiotherapy. iii. The 5-HT3 antagonist should only be used on the first day of cisplatin therapy with aprepitant continuing on Day 2 and Day 3. iv. The dose of dexamethasone may be adjusted due to the increased levels of dexamethasone when combined with aprepitant.



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