Aprepitant

About Aprepitant

• Aprepitant, initially approved by the FDA on March 26, 2003, is a substance P/neurokinin 1 (NK1) receptor antagonist. 
• It is available in various formulations, including capsules, oral suspension, and injection. 

Aprepitant Oral Suspension:

• This drug is used with other antiemetic drugs, is indicated for patients aged 6 months and older. 
• It is used to prevent acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy (HEC), including high-dose cisplatin, as well as for the prevention of nausea and vomiting related to moderately emetogenic cancer chemotherapy (MEC).

Aprepitant Capsule: 

• When the capsule is combined with other antiemetic agents, effectively prevents nausea and vomiting in patients aged 12 and older undergoing highly emetogenic cancer chemotherapy (HEC) with high-dose cisplatin, as well as moderately emetogenic cancer chemotherapy (MEC). 
• Additionally, It is prescribed for the prevention of postoperative nausea and vomiting (PONV) in adults.

Aprepitant Injection:

• It is prescribed for the prevention of postoperative nausea and vomiting (PONV) in adults.
• Aprepitant acts as a centrally acting antiemetic by selectively antagonizing the G-protein-coupled neurokinin-1 (NK1) receptor. These receptors are located in brainstem regions associated with the vomiting reflex, such as the central pattern generator, nucleus tractus solitarius, and area postrema. 
• By competitively blocking these receptors, it prevents substance P, a nociceptive neurotransmitter, from binding to NK1 receptors. 
• This mechanism reduces the likelihood of vomiting in patients experiencing chemotherapy-induced nausea and vomiting (CINV) or postoperative nausea and vomiting (PONV).

Strength: 

Aprepitant capsule is available in strengths of  40 mg; 80 mg; 125 mg. Oral suspension in 125 mg and the injection in 32 mg/4.4 mL (7.2 mg/mL) in single-dose vial. 

Recommended Dosage:

These capsules and oral suspension can be taken with or without food. For the capsules, they should be swallowed whole. The oral suspension is prepared by the healthcare provider and dispensed to the patient or caregiver in an oral dispenser, which should be stored in the refrigerator until use.

Once ready, the dispenser is placed in the patient’s mouth along the inner cheek, and the medicine is dispensed slowly. The prepared dose can be kept at room temperature for up to 3 hours before use and must be used within 72 hours of preparation. Any remaining doses after 72 hours should be discarded.

Capsules:

• For prevention of chemotherapy-induced nausea and vomiting (CINV) in adults and pediatric patients 12 years of age and older, the typical dose is a single Aprepitant 125 mg capsule taken orally on Day 1, followed by Aprepitant 80 mg capsule once daily on Days 2 and 3.
• For prevention of postoperative nausea and vomiting (PONV) in adults: The recommended dose is a single Aprepitant 40 mg capsule taken orally 1 to 3 hours before induction of anesthesia.
• Consult your healthcare provider for the exact dosing details. 

Oral Suspension:

• Oral suspension is prescribed for pediatric patients aged 6 months to less than 12 years, as well as for both pediatric and adult patients who have difficulty swallowing capsules. 
• The dosage of the oral suspension is determined by the patient’s weight, with a maximum of Aprepitant oral 125 mg on Day 1 and 80 mg on Days 2 and 3. 
• It is not recommended to use this medicine in pediatric patients weighing less than 6 kg. 
• It is essential to consult a healthcare provider to establish the correct dose.

Capsules and oral suspension should be administered 1 hour before chemotherapy on Days 1, 2, and 3. If chemotherapy is not scheduled on Days 2 and 3, both formulations should be taken in the morning.

Injection:

• The recommended dosage is 32 mg given as a 30-second intravenous injection before the start of anesthesia induction.
• It’s important to follow the dosage instructions provided by a healthcare provider or as indicated on the medication label.

Important:

Before starting the treatment, it is important to inform your doctor about all your pre-existing medical conditions. Report to your doctor if you get any adverse reactions after taking this medicine. 

Warnings & Precaution:

• Aprepitant is contraindicated in patients with hypersensitivity to any component and in those taking pimozide due to potential QT prolongation. It acts as a substrate, weak-to-moderate inhibitor, and inducer of CYP3A4. Concomitant use with other CYP3A4 substrates may alter plasma concentrations, while combination with strong or moderate CYP3A4 inhibitors could increase the drug levels, potentially leading to adverse reactions. 
• Conversely, using this medicine with strong CYP3A4 inducers may decrease this drug’s plasma concentrations and efficacy. Hypersensitivity reactions, including anaphylaxis, have been reported with the treatment.
• For patients taking warfarin, a CYP2C9 substrate, there is a risk of reduced INR (International Normalized Ratio) of prothrombin time. It is advisable to monitor INR levels within 2 weeks, especially at 7 to 10 days after starting the treatment.
• The effectiveness of hormonal contraceptives may be diminished for 28 days after taking the medicine. It is recommended to utilize alternative or supplementary non-hormonal contraceptive methods during this time.

Common Aprepitant Side Effects:

• Fatigue
• Diarrhea
• Asthenia
• Dyspepsia
• Abdominal pain
• Hiccups
• Decreased white blood cell count
• Dehydration
• Increased alanine aminotransferase
• Neutropenia
• Headache
• Decreased appetite
• Cough
• Hemoglobin decreased
• Dizziness
• Constipation
• Hypotension

Use in Specific Population

• Insufficient data exist on the use of Aprepitant in pregnant women to determine any associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 
• Due to its alcohol content, this medicine should be avoided in pregnant women. 
• There is also a lack of information regarding the presence of the medicine in human milk, its effects on breastfed infants, or milk production. 
• The safety and effectiveness of both the capsule and oral suspension formulations for preventing nausea and vomiting associated with highly emetogenic or moderately emetogenic chemotherapy have not been established in patients younger than 6 months. 
• Similarly, there is no established safety and effectiveness for the prevention of postoperative nausea and vomiting in pediatric patients with either formulation. 
• Additionally, the safety and effectiveness of the injection have not been determined in pediatric patients. 
• No dosage adjustments are required for patients with any degree of renal impairment or those with end-stage renal disease (ESRD) undergoing hemodialysis. 
• Similarly, no clinically significant changes in the pharmacokinetics are anticipated in patients with any degree of renal impairment following a single dose of 32 mg administered intravenously. 
• Furthermore, no dosage adjustments are necessary for patients with mild to moderate or severe hepatic impairment.

Storage and Handling 

• Capsules: Store at 20-25°C (68-77°F) as per USP Controlled Room Temperature guidelines.
• Oral Suspension: Keep unopened pouch at 20-25°C (68-77°F) with excursions allowed between 15-30°C (59-86°F). Store in the original container. Do not open until ready for use. If the dose is not immediately administered after preparation, the filled oral dosing dispenser should be stored in the refrigerator at temperatures between 36°F and 46°F (2°C-8°C) for up to 72 hours before use. 
• When dispensing the doses to the patient or caregiver, they should be instructed to refrigerate the oral dosing dispensers until ready for administration. When ready to use, the mixture can be kept at room temperature, between 68°F and 77°F (20°C-25°C), for up to 3 hours. 
• Injection: Store the injection in the refrigerator at temperatures between 2°C to 8°C (36°F to 46°F). It can be kept at room temperature, ranging from 20°C to 25°C (68°F to 77°F), for up to 60 days. Avoid freezing the medicine. 10 single-dose vials per carton. 
• Keep the medicine away from pets and children.