Aprepitantum
Aprepitantum Uses, Dosage, Side Effects, Food Interaction and all others data.
Aprepitantum is a selective high affinity antagonist of human substance P neurokinin 1 (NK1) receptors. When substance P attaches to these receptors, it causes nausea and vomiting. Aprepitantum stops substance P from binding to the NK1 receptors. By blocking the receptors, Aprepitantum can prevent nausea and vomiting, which often happens after chemotherapy or as a complication of surgery.
Aprepitantum, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitantum is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitantum has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).
| Trade Name | Aprepitantum |
| Availability | Prescription only |
| Generic | Aprepitant |
| Aprepitant Other Names | Aprepitant, Aprépitant, Aprepitantum |
| Related Drugs | lorazepam, ondansetron, Zofran, dexamethasone, Ativan, metoclopramide |
| Type | |
| Formula | C23H21F7N4O3 |
| Weight | Average: 534.4267 Monoisotopic: 534.150187993 |
| Protein binding | Protein binding is reported to be >95%. |
| Groups | Approved, Investigational |
| Therapeutic Class | Anti-emetic drugs |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Aprepitantum is used for-
- Prevention of postoperative nausea and vomiting (PONV)
- Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)
Aprepitantum is also used to associated treatment for these conditions: Nausea and vomiting
How Aprepitantum works
Aprepitantum 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 Aprepitantum have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitantum 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
Aprepitantum dosage
Post Operative Nausea and Vomiting
The recommended oral dosage of Aprepitantum 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: Aprepitantum 125mg orally, Dexamethasone 12 mg orally, 5-HT3 antagonist (Ondansetron): 24 mg 30 minutes before the start of chemotherapy.
Day 2: Aprepitantum 80 mg orally, Dexamethasone 8 mg orally
Day 3: Aprepitantum 80 mg orally, Dexamethasone 8 mg orally
Day 4: Dexamethasone 8 mg orally
*Aprepitantum 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: Aprepitantum 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: Aprepitantum 80 mg orally, 5-HT3 antagonist (Ondansetron): 8 mg tablet twice a day
Day 3: Aprepitantum 80 mg orally, 5-HT3 antagonist (Ondansetron): 8 mg tablet twice a day
*Aprepitantum 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.
Aprepitantum 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
Aprepitantum is a substrate, a weak-to-moderate (dose dependent) inhibitor, and an inducer of CYP3A4. Aprepitantum is also an inducer of CYP2C9. Precautions should be taken while coadministering Aprepitantum 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 Aprepitantum, the efficacy of hormonal contraceptives during and for 28 days following the last dose of Aprepitantum may be reduced. Alternative or back-up methods of contraception should be used during treatment with Aprepitantum and for 1 month following the last dose of Aprepitantum.
Food Interaction
- Take with or without food. The absorption is unaffected by food.
Aprepitantum 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
Aprepitantum Disease Interaction
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
Aprepitantum is eliminated primarily by metabolism; aprepitant is not renally excreted. Aprepitantum 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
Aprepitantum is contraindicated in patients who are hypersensitive to any component of the product. Aprepitantum 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 Aprepitantum. Single doses up to 600 mg of Aprepitantum were generally well tolerated in healthy subjects. Drowsiness and headache can be seen due to overdose. In the event of overdose, Aprepitantum should be discontinued. General supportive treatment and monitoring should be provided. Because of the antiemetic activity of Aprepitantum, medicine-induced emesis may not be effective. Aprepitantum cannot be removed by hemodialysis.
Interaction with other Medicine
Aprepitantum is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitantum is also an inducer of CYP2C9. Precautions should be taken while coadministering Aprepitantum 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 Aprepitantum, the efficacy of hormonal contraceptives during and for 28 days following the last dose of Aprepitantum may be reduced. Alternative or back-up methods of contraception should be used during treatment with Aprepitantum and for 1 month following the last dose of Aprepitantum.
Innovators Monograph
You find simplified version here Aprepitantum
Aprepitantum contains Aprepitant see full prescribing information from innovator Aprepitantum Monograph, Aprepitantum MSDS, Aprepitantum FDA label
