Usage
Aprepitant is prescribed for the prevention of:
- Chemotherapy-induced nausea and vomiting (CINV): For both highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).
- Postoperative nausea and vomiting (PONV).
Pharmacological Classification: Antiemetic. Specifically, it is a substance P/neurokinin 1 (NK1) receptor antagonist.
Mechanism of Action: Aprepitant blocks the binding of Substance P to the NK1 receptors in the brain and gastrointestinal tract. Substance P plays a significant role in the emetic response. By blocking its action, Aprepitant helps prevent nausea and vomiting.
Alternate Names
International Nonproprietary Name (INN): Aprepitant
Brand Names: Emend, Cinvanti (intravenous formulation)
How It Works
Pharmacodynamics: Aprepitant exerts its antiemetic effect by antagonizing the NK1 receptor, thus inhibiting the emetic effects of Substance P. This action is central to its efficacy in preventing CINV and PONV.
Pharmacokinetics:
- Absorption: Aprepitant is well-absorbed orally, reaching peak plasma concentration in about 4 hours.
- Metabolism: Primarily metabolized by the liver via CYP3A4 enzymes. It also acts as a moderate inhibitor of CYP3A4 and a weak inducer of CYP2C9. These interactions are dose and time-dependent.
- Elimination: Primarily eliminated through the liver, with only a small portion excreted unchanged in urine and feces. The elimination half-life is about 9 to 13 hours.
Mode of Action: Aprepitant competitively binds to the NK1 receptor, preventing Substance P from binding and triggering the emetic reflex pathway.
Receptor Binding: Selective antagonist for the neurokinin 1 (NK1) receptor.
Enzyme Inhibition/Induction: Moderate inhibitor of CYP3A4, weak inducer of CYP2C9.
Elimination Pathways: Primarily hepatic metabolism and biliary excretion, with a small amount excreted renally.
Dosage
Standard Dosage
Adults:
- CINV (HEC and MEC): 125 mg orally 1 hour before chemotherapy on Day 1, followed by 80 mg orally once daily on Days 2 and 3.
- PONV: 40 mg orally within 3 hours before induction of anesthesia.
Children:
- CINV (HEC and MEC) (6 months to <12 years): 3 mg/kg (up to a maximum of 125 mg) orally on Day 1, followed by 2 mg/kg (up to a maximum of 80 mg) orally on Days 2 and 3. Administer 1 hour before chemotherapy or in the morning if chemotherapy is not given on Days 2 and 3.
- CINV (HEC and MEC) (12 years and older): Same as adult dosing.
- PONV: Dose must be determined by the doctor.
Special Cases:
- Elderly Patients: No dose adjustment is necessary.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary for mild to moderate impairment. Use with caution in severe hepatic impairment.
- Patients with Comorbid Conditions: Exercise caution based on specific comorbidity and potential drug interactions.
Clinical Use Cases
Aprepitant is primarily used in the oncological setting for the prevention of CINV, but it’s also used for PONV in surgical settings. Its use in other specific medical settings like intubation, mechanical ventilation, ICU use, or emergency situations is not routinely indicated and may be considered on a case-by-case basis based on clinical judgment.
Dosage Adjustments
Dosage adjustments may be necessary based on concomitant medications, particularly those metabolized by or affecting CYP3A4 and CYP2C9. Refer to drug interaction information for specific guidance.
Side Effects
Common Side Effects:
Fatigue, headache, hiccups, diarrhea, constipation, indigestion, loss of appetite, and asthenia.
Rare but Serious Side Effects:
Allergic reactions (rash, hives, itching, swelling), Stevens-Johnson Syndrome, and QT interval prolongation (when co-administered with certain drugs).
Long-Term Effects:
No significant long-term effects have been reported with the short-term use typically employed for CINV and PONV.
Adverse Drug Reactions (ADR):
Severe allergic reactions, Stevens-Johnson Syndrome.
Contraindications
- Hypersensitivity to aprepitant.
- Concurrent use with pimozide, cisapride, astemizole, terfenadine, and flibanserin.
Drug Interactions
Aprepitant interacts with numerous drugs, primarily through its effects on CYP3A4 and CYP2C9.
- CYP450 Interactions: Aprepitant is a moderate inhibitor of CYP3A4. It can also induce CYP2C9 and, to a lesser extent, CYP3A4.
- Medications: Warfarin, hormonal contraceptives, dexamethasone, certain chemotherapeutic agents (e.g. ifosfamide), and many others. Consult a comprehensive drug interaction resource before co-prescribing.
- OTC Drugs and Supplements: St. John’s Wort.
- Food and Lifestyle Factors: No significant interactions.
Pregnancy and Breastfeeding
- Pregnancy: There are limited human data. Animal studies show no adverse effects. Use only if the potential benefit outweighs the potential risk to the fetus. Non-hormonal backup method of contraception recommended.
- Breastfeeding: Aprepitant is excreted in rat milk. Not known if it is excreted in human milk. Breastfeeding is not recommended during treatment.
Drug Profile Summary
- Mechanism of Action: NK1 receptor antagonist.
- Side Effects: Fatigue, headache, hiccups, diarrhea, constipation, allergic reactions.
- Contraindications: Hypersensitivity, concomitant use with pimozide, cisapride, astemizole, terfenadine and flibanserin.
- Drug Interactions: Numerous, consult a comprehensive drug interaction resource.
- Pregnancy & Breastfeeding: Limited human data; caution advised.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Monitor for adverse effects and drug interactions. For patients on warfarin, monitor INR.
Popular Combinations
Aprepitant is often used in combination with a 5-HT3 receptor antagonist (e.g., ondansetron) and a corticosteroid (e.g., dexamethasone) for the prevention of CINV.
Precautions
- Monitor for hypersensitivity reactions.
- Caution in patients with severe hepatic impairment.
- Use effective contraception during treatment and for one month after the last dose.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aprepitant?
A: See detailed dosage section above, covering adult, pediatric, and special populations.
Q2: How should Aprepitant be administered?
A: Orally in capsule form, with or without food. Cinvanti is administered intravenously.
Q3: What are the most common side effects?
A: Fatigue, headache, hiccups, diarrhea, and constipation.
Q4: Does Aprepitant interact with other medications?
A: Yes, it interacts with numerous drugs via CYP3A4 and CYP2C9. Consult a drug interaction checker.
Q5: Can Aprepitant be used in pregnant or breastfeeding women?
A: Limited data in pregnancy; use with caution. Breastfeeding is not recommended.
Q6: What is the mechanism of action of Aprepitant?
A: It’s an NK1 receptor antagonist, blocking the action of Substance P.
Q7: What should I monitor in patients taking Aprepitant?
A: Monitor for side effects and drug interactions. Monitor INR for patients on warfarin.
Q8: What is the difference between Aprepitant and Fosaprepitant?
A: Fosaprepitant is a prodrug of aprepitant, administered intravenously.
Q9: Are there any contraindications to using Aprepitant?
A: Yes, hypersensitivity and concurrent use of certain drugs like pimozide, cisapride, astemizole, terfenadine and flibanserin are contraindicated.
Q10: Is dose adjustment necessary for elderly patients?
A: No.
