| Aprepitant Pharmacology |
| Aprepitant |
| About Aprepitant |
| Antiemetic belongs to a class of drugs called substance P antagonists (SPA). |
| Mechanism of Action of Aprepitant |
| Aprepitant is an antiemetic which acts as a substance P/neurokinin 1 (NK1) receptor antagonist. It also enhances antiemetic activity of 5HT3 antagonists and corticosteroid. |
| Pharmacokinets of Aprepitant |
| 1.Absorption: Absorbed in the GI tract. Plasma concentrations peak after about 4 hr. Bioavailability: About 60-65%. 2.Distribution: Vd: About 70 L; crosses the blood-brain barrier Plasma protein binding: >95%. 3.Metabolism: Undergoes extensive hepatic metabolism via oxidation by cytochrome P450 isoenzyme CYP3A4, the isoenzymes CYP1A2 and CYP2C19 mediate minor metabolic pathways. 4.Excretion: Primarily by metabolism. |
| Onset of Action for Aprepitant |
| N/A |
| Duration of Action for Aprepitant |
| N/A |
| Half Life of Aprepitant |
| About 9-13 hr. |
| Side Effects of Aprepitant |
| 1.Headache 2.Dizziness 3.Nausea 4.Vomiting 5.Hiccups 6.Thirst 7.Constipation 8.Abdominal pain 9.Dyspepsia 10.Diarrhea 11.Dehydration 12.Fatigue 13.Cough 14.Hypotension 15.Hypertension 16.Angioedema 17.Elevated ALT and AST levels 18.Proteinuria 19.Increased BUN. 20.Potentially Fatal: Hypersensitivity reactions, Steven-Johnsons syndrome. |
| Contra-indications of Aprepitant |
| Concomitant use with astemizole, cisapride, pimozide, terfenadine. |
| Special Precautions while taking Aprepitant |
| 1.Moderate to severe hepatic impairment 2.Concurrent use with strong/moderate CYP3A4 inhibitors, inducers or substrates 3.Monitor INR closely for patients on warfarin |
| Pregnancy Related Information |
| Use with caution |
| Old Age Related Information |
| Use with caution |
| Breast Feeding Related Information |
| Not recommended |
| Children Related Information |
| Not recommended |
| Indications for Aprepitant |
| 1.To prevention of chemotherapy-induced nausea and vomiting 2.Postoperative nausea and vomiting |
| Interactions for Aprepitant |
| 1.Concurrent use with CYP3A4 inhibitors (e.g. clarithromycin, troleandomycin, diltiazem, verapamil, itraconazole, ketoconazole, nefazodone, ritonavir, nelfinavir) may lead to increased plasma levels of Aprepitant 2.Concurrent use with CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, primidone, phenobarbital) may lead to reduced efficacy of Aprepitant 3.May decrease concentrations of CYP2C9 substrates e.g. phenytoin, tolbutamide, warfarin 4.May increase plasma levels of dexamethasone and methylprednisolone 5.May increase plasma levels of benzodiazepine (e.g. midazolam, diazepam, alprazolam) 6.Serum concentrations of colchicine may increase with Aprepitant 7.May increase toxicity of chemotherapy drug metabolised by CYP3A4 e.g. docetaxel, etoposide, ifosfamide, imatinib, paclitaxel, vincristine, vinblastin 8.May increase levels of ergot derivatives resulting in ergotism 9.May reduce efficacy of oral contraceptives, use additional methods of contraception during treatment and for at least 1 mth following the last dose of Aprepitant. 10.Potentially Fatal: May result in increased serum levels of astemizole, cisapride, pimozide and terfenadine which can lead to life-threatening torsade de pointes arrhythmias. |
| Typical Dosage for Aprepitant |
| Oral Prophylaxis of chemotherapy-induced nausea and vomiting Adult: To be given for 3 days as part of a regimen containing a corticosteroid and a 5HT3 antagonist. Day 1: 125 mg (1 hr before chemotherapy); days 2 and 3: 80 mg once daily. Prophylaxis of postoperative nausea and vomiting Adult: 40 mg within 3 hr prior to induction of anaesthesia. |
| Schedule of Aprepitant |
| N/A |
| Storage Requirements for Aprepitant |
| Oral: Store at room temperature 20-25?C (68-77?F). |
| Effects of Missed Dosage of Aprepitant |
| N/A |
| Effects of Overdose of Aprepitant |
| N/A |