Fosaprepitant Dimeglumine

Fosaprepitant dimeglumine injection is an antiemetic (anti-nausea) medication used to prevent chemotherapy-induced nausea and vomiting in adults and in children as young as 6 months old.

• Prevents both acute (within 24 hours) and delayed (days 2–5) nausea and vomiting caused by highly emetogenic chemotherapy (HEC), including high-dose cisplatin — approved for Emend, Focinvez, and Fosaprepitant Dimeglumine injection.
• Prevents delayed nausea and vomiting caused by moderately emetogenic chemotherapy (MEC) — approved for Emend, Focinvez, and Fosaprepitant Dimeglumine injection.
• Approved for use in adults and children 6 months to 17 years of age weighing at least 6 kg.
• Always used as part of a combination regimen with other anti-nausea medicines; it is not a stand-alone treatment and has not been studied for treating nausea that has already begun.

Fosaprepitant is a prodrug — your body converts it into its active form, aprepitant, within about 30 minutes of the IV infusion finishing. Aprepitant works by selectively blocking NK1 (neurokinin-1) receptors in the brain — these receptors play a key role in triggering the vomiting reflex in response to chemotherapy. By occupying these receptors, aprepitant prevents the signal from getting through, suppressing both the immediate and the slower, delayed wave of nausea. It also enhances the anti-nausea effects of other medicines given at the same time, such as ondansetron and dexamethasone.

Fosaprepitant dimeglumine is given as an intravenous (IV) infusion by a healthcare professional — you will not be self-administering it at home. For adults, it is infused over 20 to 30 minutes on the first day of a chemotherapy cycle, completing roughly 30 minutes before chemotherapy begins. For adolescents (12–17 years), the infusion runs over 30 minutes; for younger children (6 months to under 12 years), it runs over 60 minutes through a central venous catheter.

• It is given on Day 1 of the chemotherapy cycle as part of a combination anti-nausea regimen.
• For some pediatric patients on multi-day chemotherapy, additional doses of a related oral medicine (aprepitant) may be used on subsequent days.
• Your oncology team will determine the exact schedule based on your chemotherapy regimen — always follow their instructions.

The most common side effects reported with fosaprepitant dimeglumine injection include:

• Fatigue — feeling more tired than usual
• Diarrhea
• Neutropenia — low white blood cell count, raising infection risk
• Asthenia — general weakness
• Anemia — low red blood cell count
• Peripheral neuropathy — tingling or numbness in hands or feet
• Leukopenia — low white blood cell count overall
• Infusion site reactions — pain, irritation, redness, or in rare cases, vein inflammation at the IV site

More serious reactions — including severe allergic responses (anaphylaxis), significant infusion site tissue damage (necrosis or vasculitis), and rare severe skin reactions — require immediate medical attention. Seek help right away if you notice difficulty breathing, flushing, low blood pressure, or a rapidly worsening skin rash.

• Serious allergic reactions (including anaphylaxis): Can occur during or shortly after the infusion. Symptoms include flushing, skin redness, difficulty breathing, low blood pressure, or fainting. The infusion must be stopped immediately and you should not receive this drug again if this happens.
• Infusion site reactions: Range from mild pain and irritation to severe thrombophlebitis (vein inflammation), vasculitis (blood vessel inflammation), and necrosis (tissue damage), particularly when given with vesicant (tissue-damaging) chemotherapy. Healthcare providers infuse into larger veins to minimize this risk.
• Drug interactions via CYP3A4: Fosaprepitant affects how many other drugs are processed by the liver. This can raise or lower levels of other medications to a clinically important degree — see the interactions section.
• Warfarin and bleeding risk: This drug can lower the effectiveness of warfarin, reducing blood-clotting protection. INR levels must be monitored closely in the two weeks after each treatment cycle.
• Reduced effectiveness of hormonal contraceptives: Birth control pills, patches, implants, and certain IUDs may become less effective during treatment and for 28 days after the last dose. A non-hormonal backup method is required during this window.

Fosaprepitant dimeglumine interacts with a number of medications because it affects a key liver enzyme (CYP3A4) that processes many drugs:

• Pimozide — strictly contraindicated; combination can cause dangerous, potentially fatal heart rhythm problems (QT prolongation).
• Warfarin — fosaprepitant can lower warfarin's effect, raising the risk of blood clots; requires close INR monitoring for 2 weeks after each cycle.
• Hormonal contraceptives (pills, patches, implants, certain IUDs) — reduced effectiveness; use a backup method during treatment and for 1 month after.
• Benzodiazepines (e.g., midazolam, alprazolam, triazolam) — levels may increase, heightening sedation risk; monitor for increased side effects.
• Dexamethasone and methylprednisolone — levels are increased by fosaprepitant; doses of these steroids are typically reduced when co-administered.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, nefazodone) — significantly raise aprepitant levels; avoid combining.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) — can reduce aprepitant levels enough to make fosaprepitant less effective; avoid combining.
• Certain chemotherapy agents (e.g., vinblastine, vincristine, ifosfamide) — fosaprepitant may increase their exposure; monitor for increased chemo-related toxicity.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Allergy: Do not use if you have had a hypersensitivity reaction to fosaprepitant, aprepitant, or any component of the product.
• Pimozide use: This combination is absolutely contraindicated — inform your care team of all medications before starting.
• All medications: Share a complete medication list with your care team, including prescriptions, over-the-counter drugs, vitamins, and herbal products.
• Pregnancy: There are insufficient human data on safety during pregnancy; animal studies showed the drug crosses the placenta. Discuss risks and benefits with your doctor.
• Breastfeeding: It is unknown whether this drug passes into human breast milk. Discuss with your doctor to weigh benefits and risks.
• Hormonal contraception: Inform your doctor if you use any hormonal birth control — a backup method is needed during treatment and for one month after.
• Liver disease: Mild to moderate liver impairment does not require dose adjustment; patients with severe liver disease should be monitored closely as there is limited safety data.
• Children under 6 months: Safety and effectiveness have not been established in this age group.
• Older adults (65+): Drug levels may be slightly higher, though this is not considered clinically meaningful; use with general caution given the likelihood of other health conditions and medications.

There is no specific antidote for fosaprepitant overdose. If an overdose occurs, the infusion should be stopped and supportive medical care provided. Because the drug itself has anti-nausea activity, trying to induce vomiting would not be helpful. Aprepitant is not removed by hemodialysis (kidney dialysis machine).

Fosaprepitant is rapidly converted to aprepitant after IV infusion, and the anti-nausea effects are due to aprepitant. Aprepitant selectively blocks NK1 (neurokinin-1) receptors in the brain — the key pathway chemotherapy uses to trigger vomiting. Studies in humans and animals confirm it crosses the blood-brain barrier and occupies these receptors directly. At the doses used clinically, fosaprepitant does not meaningfully affect heart electrical activity (it did not prolong the QTc interval in a dedicated cardiac study).

After a 20-minute IV infusion, fosaprepitant is converted to aprepitant within about 30 minutes — so the active drug gets to work quickly. Aprepitant is more than 95% bound to proteins in the blood and distributes into tissues, with a volume of distribution of about 70 liters. It is broken down mainly by the liver enzyme CYP3A4, with smaller contributions from CYP1A2 and CYP2C19; it is not cleared by the kidneys. The active drug has a half-life of roughly 9 to 13 hours, meaning it stays active in the body well into the period when delayed nausea typically occurs. Elimination occurs through metabolism, with byproducts leaving the body in both urine and stool.

Fosaprepitant for Injection vials must be refrigerated, store at 2°C to 8°C (36°F to 46°F).