Aprepitant

Uses

Aprepitant is used for-

- Prevention of postoperative nausea and vomiting (PONV)

- Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

Aprepitant is also used to associated treatment for these conditions: Nausea and vomiting

How Aprepitant works

Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT₃-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis.

Dosage

Aprepitant dosage

Post Operative Nausea and Vomiting

The recommended oral dosage of Aprepitant is 40 mg within 3 hours prior to induction of anesthesia.

Chemotherapy Induced Nausea and Vomiting

The following regimen should be used for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy:

Day 1: Aprepitant 125mg orally, Dexamethasone 12 mg orally, 5-HT3 antagonist (Ondansetron): 24 mg 30 minutes before the start of chemotherapy.

Day 2: Aprepitant 80 mg orally, Dexamethasone 8 mg orally

Day 3: Aprepitant 80 mg orally, Dexamethasone 8 mg orally

Day 4: Dexamethasone 8 mg orally

*Aprepitant is administered orally 1 hour prior to chemotherapy treatment on Day 1 and in the morning on Days 2 and 3. **Dexamethasone is administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. The dose of dexamethasone accounts for drug interactions.

The following regimen should be used for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy:

Day 1: Aprepitant 125mg orally, Dexamethasone 12 mg orally, 5-HT3 antagonist (Ondansetron): one 8 mg tablet 30 minutes before chemotherapy followed by an 8 mg dose 8 hours later.

Day 2: Aprepitant 80 mg orally, 5-HT3 antagonist (Ondansetron): 8 mg tablet twice a day

Day 3: Aprepitant 80 mg orally, 5-HT3 antagonist (Ondansetron): 8 mg tablet twice a day

*Aprepitant is administered orally 1 hour prior to chemotherapy treatment on Day 1 and in the morning on Days 2 and 3. **Dexamethasone is administered 30 minutes prior to chemotherapy treatment on Day 1. The dose of dexamethasone accounts for drug interactions.

Aprepitant may be taken with or without food. No dosage adjustment is necessary for the elderly patients.

Patients with Renal Impairment- No dosage adjustment is necessary for patients with renal impairment or for patients with end stage renal disease (ESRD) undergoing hemodialysis.

Patients with Hepatic Impairment-No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. There are no clinical data in patients with severe hepatic impairment .

Side Effects

Constipation, Hypotension, Pruritus, Pyrexia

Interaction

Aprepitant is a substrate, a weak-to-moderate (dose dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Precautions should be taken while coadministering Aprepitant with drugs that use CYP3A4 or CYP2C9, for example- Warfarin, Tolbutamide, Phenytoin, Ketoconazole, Itraconazole, Nefazodone, Troleandomycin, Clarithromycin, Ritonavir, Nelfinavir, Diltiazem, Rifampin, Carbamazepine etc. Upon coadministration with Aprepitant, the efficacy of hormonal contraceptives during and for 28 days following the last dose of Aprepitant may be reduced. Alternative or back-up methods of contraception should be used during treatment with Aprepitant and for 1 month following the last dose of Aprepitant.

Food Interaction

• Take with or without food. The absorption is unaffected by food.

Aprepitant Drug Interaction

Unknown: charcoal, charcoal, diphenhydramine, diphenhydramine, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, prochlorperazine, prochlorperazine, meperidine, meperidine, sodium iodide, sodium iodide, pregabalin, pregabalin, acetaminophen, acetaminophen, cholecalciferol, cholecalciferol, ondansetron, ondansetron

Aprepitant Disease Interaction

Moderate: liver disease

Volume of Distribution

• 70 L

Elimination Route

The mean absolute oral bioavailability of aprepitant is approximately 60 to 65%.

Half Life

9-13 hours

Clearance

• Apparent plasma cl=62-90 mL/min

Elimination Route

Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted. Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk.

Pregnancy & Breastfeeding use

Pregnancy Category B: This drug should be used during pregnancy only if clearly needed.

It is not known whether this drug is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug based on patient’s importance.

Contraindication

Aprepitant is contraindicated in patients who are hypersensitive to any component of the product. Aprepitant should not be used concurrently with Pimozide, Terfenadine, Astemizole & Cisapride.

Special Warning

Patients with Renal Impairment: No dosage adjustment is necessary for patients with renal impairment or for patients with end stage renal disease (ESRD) undergoing hemodialysis.

Patients with Hepatic Impairment: No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. There are no clinical data in patients with severe hepatic impairment .

Acute Overdose

No specific information is available on the treatment of overdosage with Aprepitant. Single doses up to 600 mg of Aprepitant were generally well tolerated in healthy subjects. Drowsiness and headache can be seen due to overdose. In the event of overdose, Aprepitant should be discontinued. General supportive treatment and monitoring should be provided. Because of the antiemetic activity of Aprepitant, medicine-induced emesis may not be effective. Aprepitant cannot be removed by hemodialysis.

Interaction with other Medicine

Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Precautions should be taken while coadministering Aprepitant with drugs that use CYP3A4 or CYP2C9, for example.-Warfarin, Tolbutamide, Phenytoin, Ketoconazole, Itraconazole, Nefazodone, Troleandomycin, Clarithromycin, Ritonavir, Nelfinavir, Diltiazem, Rifampin, Carbamazepine etc.

Upon coadministration with Aprepitant, the efficacy of hormonal contraceptives during and for 28 days following the last dose of Aprepitant may be reduced. Alternative or back-up methods of contraception should be used during treatment with Aprepitant and for 1 month following the last dose of Aprepitant.

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