Apretero

Uses

Apretero is used for-

- Prevention of postoperative nausea and vomiting (PONV)

- Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

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

How Apretero works

Apretero 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 Apretero have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Apretero 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

Apretero dosage

Post Operative Nausea and Vomiting

The recommended oral dosage of Apretero 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: Apretero 125mg orally, Dexamethasone 12 mg orally, 5-HT3 antagonist (Ondansetron): 24 mg 30 minutes before the start of chemotherapy.

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

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

Day 4: Dexamethasone 8 mg orally

*Apretero 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: Apretero 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: Apretero 80 mg orally, 5-HT3 antagonist (Ondansetron): 8 mg tablet twice a day

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

*Apretero 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.

Apretero 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

Apretero is a substrate, a weak-to-moderate (dose dependent) inhibitor, and an inducer of CYP3A4. Apretero is also an inducer of CYP2C9. Precautions should be taken while coadministering Apretero 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 Apretero, the efficacy of hormonal contraceptives during and for 28 days following the last dose of Apretero may be reduced. Alternative or back-up methods of contraception should be used during treatment with Apretero and for 1 month following the last dose of Apretero.

Food Interaction

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

Apretero 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

Apretero 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

Apretero is eliminated primarily by metabolism; aprepitant is not renally excreted. Apretero 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

Apretero is contraindicated in patients who are hypersensitive to any component of the product. Apretero 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 Apretero. Single doses up to 600 mg of Apretero were generally well tolerated in healthy subjects. Drowsiness and headache can be seen due to overdose. In the event of overdose, Apretero should be discontinued. General supportive treatment and monitoring should be provided. Because of the antiemetic activity of Apretero, medicine-induced emesis may not be effective. Apretero cannot be removed by hemodialysis.

Interaction with other Medicine

Apretero is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Apretero is also an inducer of CYP2C9. Precautions should be taken while coadministering Apretero 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 Apretero, the efficacy of hormonal contraceptives during and for 28 days following the last dose of Apretero may be reduced. Alternative or back-up methods of contraception should be used during treatment with Apretero and for 1 month following the last dose of Apretero.

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