Fosaprepitant (Injection)

INTRODUCTION

Indications

Prevention of nausea and vomiting associated with emetogenic chemotherapy.

Action

Acts as a selective antagonist at substance P/neurokinin₁ (NK1) receptors in the brain. Therapeutic Effects: Decreased nausea and vomiting associated with chemotherapy.

Adverse Reactions/Side Effects

CNS: dizziness, fatigue, weakness. GI: diarrhea. Misc: hiccups.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor improvements in GI symptoms (decreased nausea and vomiting, increased appetite) to help document whether drug therapy is successful.

• Assess dizziness, fatigue, or weakness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.

Patient/Client-Related Instruction

• Instruct patient to report bothersome GI side effects such as severe or prolonged diarrhea or hiccups.

Pharmacokinetics

Absorption: Following IV administration, fosaprepitant is rapidly converted to aprepitant, the active component.

Distribution: Crosses the blood-brain barrier; remainder of distribution unknown.

Metabolism and Excretion: Mostly metabolized by the liver (CYP3A4 enzyme system); not renally excreted.

Half-life: Aprepitant—9–13 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent use with pimozide (risk of life-threatening adverse cardiovascular reactions); Lactation: May cause unwanted effects in nursing infants.

Use Cautiously in: OB: Use only if clearly needed; Pedi: Safety not established.

Interactions

Drug-Drug: Aprepitant inhibits, induces and is metabolized by the CYP3A4 enzyme system; it also induces the CYP2C9 system. Concurrent use with other medications that are metabolized by CYP3A4 may result in ↑ toxicity from these agents, including docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine, midazolam, triazolam, and alprazolam; concurrent use should be undertaken with caution. Concurrent use with drugs that significantly inhibit the CYP3A4 enzyme system, including ketoconazole, itraconazole, nefazodone, clarithromycin, ritonavir, nelfinavir, and diltiazem, may ↑ blood levels and effects of aprepitant. Concurrent use with drugs that induce the CYP3A4 enzyme system, including rifampin, carbamazepine, and phenytoin, may ↓ blood levels and effects of aprepitant. ↑ blood levels and effects of dexamethasone (regimen reflects a 50% dose reduction); a similar effect occurs with methylprednisolone (IV dose by 25%, PO dose by 50% when used concurrently). May ↓ the effects of warfarin (careful monitoring for 2 wk recommended), oral contraceptives (use alternate method), tolbutamide, and phenytoin...