Aprepitant


Generic Medicine Info
Indications and Dosage
Oral
Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: Highly emetogenic chemotherapy: 125 mg 1 hr before chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3, in combination w/ a 5-HT3 antagonist antiemetic on day 1 and dexamethasone on days 1-4. Moderately emetogenic chemotherapy: 125 mg 1 hr before chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3, in combination w/ a 5-HT3 antagonist antiemetic and dexamethasone on day 1.

Oral
Prophylaxis of postoperative nausea and vomiting
Adult: 40 mg w/in 3 hr prior to induction of anaesth.
Administration
May be taken with or without food.
Contraindications
Co-admin w/ astemizole, cisapride, pimozide, terfenadine.
Special Precautions
Moderate to severe hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Headache, constipation, diarrhoea, dyspepsia, anorexia, fatigue, hiccups, eructation, dizziness, increased ALT or AST levels, abdominal pain, oedema, tinnitus, neutropenic colitis, chills, gait disturbances, flushing, epigastric discomfort, dysgeusia, dry mouth, stomatitis, thirst, polyuria, dysuria, haematuria, urinary frequency, arthralgia, myalgia, muscular weakness, hyperglycaemia, disorientation, euphoria, anxiety, photosensitivity, skin disorders (e.g. rash, pruritus), anaemia, febrile neutropenia, HTN or hypotension, palpitations, bradycardia, hyponatraemia, hypokalaemia, insomnia, drowsiness, miosis, reduced visual acuity, wt changes, sensory disturbances, throat irritation, sneezing, abnormal bowel sounds, acid reflux, perforating duodenal ulcer, dyspnoea, cough, wheezing, hyperhidrosis, conjunctivitis, pharyngitis, resp tract infections, UTI, candidiasis, herpes simplex.
Potentially Fatal: Hypersensitivity reactions (e.g. Stevens-Johnson syndrome, anaphylaxis, angioedema).
Patient Counseling Information
This drug may cause dizziness and fatigue, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor INR/protohrombin time (in patients taking warfarin) for 2 wk (particularly at 7-10 days) following admin; signs/symptoms of hypersensitivity reaction.
Overdosage
Symptoms: Drowsiness, headache. Management: Supportive treatment.
Drug Interactions
May increase exposure of oral CYP3A4 substrates. May reduce plasma concentration of drugs metabolised by CYP2C9 isoenzyme (e.g. warfarin, phenytoin, tolbutamide). May increase exposure to corticosteroids. May reduce the efficacy of OCs. Reduced plasma levels w/ strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenobarbital). Increased plasma levels w/ CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, protease inhibitors). May enhance serum levels of tolvaptan.
Potentially Fatal: Significantly increased plasma level and potential for QT prolongation w/ astemizole, cisapride, pimozide, terfenadine.
Food Interaction
Decreased plasma levels w/ St John's wort. Increased serum concentration w/ grapefruit juice.
Action
Description: Aprepitant prevents emesis by inhibiting substance P/neurokinin 1 (NK1) receptors. It enhances the antiemetic activity of 5HT3 receptor antagonists and corticosteroids.
Pharmacokinetics:
Absorption: Absorbed in the GI tract. Bioavailability: Approx 60%. Time to peak plasma concentration: Approx 4 hr.
Distribution: Crosses the blood-brain barrier. Volume of distribution: Approx 70 L. Plasma protein binding: >95%.
Metabolism: Undergoes extensive hepatic metabolism, mainly via oxidation by CYP3A4 isoenzyme; CYP1A2 and CYP2C19 isoenzymes mediate minor metabolic pathways.
Excretion: Via urine and faeces. Terminal elimination half-life: Approx 9-13 hr.
Chemical Structure

Chemical Structure Image
Aprepitant

Source: National Center for Biotechnology Information. PubChem Database. Aprepitant, CID=135413536, https://pubchem.ncbi.nlm.nih.gov/compound/Aprepitant (accessed on Jan. 21, 2020)

Storage
Store between 20-25°C.
ATC Classification
A04AD12 - aprepitant ; Belongs to the class of other antiemetics.
References
Anon. Aprepitant. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/11/2015.

Buckingham R (ed). Aprepitant. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/11/2015.

Emend Capsule (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/11/2015.

McEvoy GK, Snow EK, Miller J et al (eds). Aprepitant/Fosaprepitant Dimeglumine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 04/11/2015.

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