Aprepitant

BRAND NAMES

Emend – the most widely known and commonly used brand 

Aprepitat – available in some markets 

Apricap – another regional brand

MECHANISM OF ACTION

Aprepitant acts as a selective neurokinin-1 (NK1) receptor antagonist that helps prevent nausea and vomiting. It works by blocking the action of Substance P, a neuropeptide that plays a central role in triggering the vomiting reflex. Normally, Substance P binds to Neurokinin-1 receptor in the brain, particularly in areas responsible for emesis. By inhibiting this binding, aprepitant effectively suppresses both acute and delayed phases of chemotherapy-induced nausea and vomiting, especially when used in combination with other antiemetic agents.

PHARMACOKINETICS

Absorption 

Aprepitant is moderately well absorbed after oral administration, with good bioavailability. Its absorption is not significantly affected by food, allowing flexible dosing.

Distribution 

Aprepitant is widely distributed throughout the body and readily crosses the blood–brain barrier to exert its effects in the central nervous system. It is highly bound to plasma proteins (greater than 95%), mainly to albumin. The drug has a relatively large volume of distribution, indicating extensive tissue uptake.

Metabolism 

Aprepitant is extensively metabolized in the liver, primarily by the enzyme Cytochrome P450 3A4. It undergoes oxidative metabolism to form multiple inactive metabolites. Aprepitant can also act as a moderate inhibitor and inducer of CYP3A4, which may lead to drug interactions with medications metabolized by this pathway.

Elimination 

Aprepitant is primarily eliminated through hepatic metabolism, with metabolites excreted mainly in the urine (about 57%) and feces (about 45%). The drug has a terminal half-life of approximately 9–13 hours, allowing once-daily dosing in most antiemetic regimens. Renal excretion of unchanged aprepitant is minimal.

PHARMACODYNAMICS 

Aprepitant exerts its therapeutic effects by selectively blocking Neurokinin-1 receptor in the central nervous system. By inhibiting the binding of Substance P, a key mediator of the vomiting reflex, aprepitant prevents both acute and delayed phases of chemotherapy-induced nausea and vomiting. Its high affinity and prolonged receptor occupancy contribute to sustained antiemetic activity, making it particularly effective when used in combination with other antiemetic agents such as 5-HT3 receptor antagonists and corticosteroids.

ADMINISTRATION 

Aprepitant is administered orally, usually as capsules or as an oral suspension. It is typically taken 1 hour before chemotherapy on the first day, followed by once-daily doses on subsequent days as part of a multi-day antiemetic regimen. The drug can be taken with or without food, and doses should be taken at the same time each day for optimal effectiveness. Careful adherence to the prescribed schedule is important to maximize prevention of both acute and delayed nausea and vomiting.

DOSAGE AND STRENGTH 

Aprepitant is available as 80 mg and 125 mg oral capsules and a 1 mg/mL oral suspension. For chemotherapy-induced nausea and vomiting, the usual regimen is 125 mg orally 1 hour before chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3. Adjustments may be made based on the chemotherapy protocol or use with other antiemetics.

DRUG INTERACTIONS 

Aprepitant is metabolized mainly by CYP3A4 and can affect CYP3A4 and CYP2C9 activity. It may interact with drugs such as chemotherapy agents, oral contraceptives, warfarin, and certain antifungals or antibiotics. These interactions can alter drug levels, so monitoring or dose adjustments may be necessary.

FOOD INTERACTIONS 

Aprepitant can be taken with or without food, as its absorption and bioavailability are not significantly affected by meals. This allows flexibility in dosing, making it convenient for patients undergoing chemotherapy or other treatments.

CONTRAINDICATIONS 

Aprepitant is contraindicated in patients with a known hypersensitivity to aprepitant or any of its components. It should also be avoided in patients taking pimozide or cisapride, as co-administration can lead to serious cardiac arrhythmias due to CYP3A4 interactions. Caution is advised when used with other medications that are highly dependent on CYP3A4 for clearance.

SIDE EFFECTS 

Aprepitant is generally well tolerated, but some patients may experience side effects. Common adverse effects include :

• fatigue

• dizziness

• hiccups

• mild headache. 

• Less frequently, it can cause elevated liver enzymes or allergic reactions. 

TOXICITY 

Aprepitant generally has a low toxicity profile at recommended doses. Overdose may cause mild symptoms such as dizziness, fatigue, or gastrointestinal upset. Severe toxic effects are rare, but caution is advised in patients with liver impairment, as reduced metabolism can increase drug exposure. Treatment of overdose is primarily supportive.