Emestop40 mg

Emestop is a selective neurokinin-1 (NK1) receptor antagonist used for the prevention of nausea and vomiting. It is not indicated for treatment of established nausea and vomiting — it is used preventively, before the emetogenic stimulus.

Established / FDA-approved uses (in combination therapy)

• Prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic cancer chemotherapy, including high-dose cisplatin, and with moderately emetogenic chemotherapy. Emestop is always used as part of a combination antiemetic regimen together with a 5-HT3 receptor antagonist (e.g. ondansetron) and a corticosteroid (e.g. dexamethasone) — it is not effective as monotherapy for this purpose.
• Prevention of postoperative nausea and vomiting (PONV) in adults, given as a single preoperative dose.

Population-specific approval

• Oral suspension: approved for CINV prevention in patients 6 months of age and older.
• Capsules: approved for CINV prevention in patients 12 years of age and older, and for PONV prevention in adults.

Each dose of Aprepitant contains aprepitant as the active pharmaceutical ingredient, formulated as:

• Hard gelatin capsules — commonly available as 40 mg, 80 mg, and 125 mg strengths.
• Powder for oral suspension (reconstituted to 125 mg/5 mL) for younger children who cannot swallow capsules.

Formulations and available strengths may vary by manufacturer and market.

Emestop is a substance P/neurokinin-1 (NK1) receptor antagonist that acts centrally in the brainstem to block the emetic signalling pathway triggered by chemotherapy and surgery. Unlike older antiemetics that target serotonin (5-HT3) or dopamine receptors, Emestop works through a distinct mechanism, which is why it is combined with a 5-HT3 antagonist and a corticosteroid for a synergistic, three-pathway approach to preventing chemotherapy-induced nausea and vomiting.

Emestop has a long plasma half-life (approximately 9 to 13 hours) and is given as a short course — typically over 3 days — timed around the chemotherapy cycle or surgical procedure, rather than as ongoing daily therapy.

Antiemetic — Neurokinin-1 (NK1) receptor antagonist. Emestop belongs to this class and is used adjunctively with 5-HT3 receptor antagonists and corticosteroids for antiemetic prophylaxis.

Pharmacodynamics

Aprepitant is a selective, high-affinity antagonist at human substance P/neurokinin-1 (NK1) receptors, with little or no affinity for serotonin (5-HT3), dopamine, or corticosteroid receptors. By blocking NK1 receptors in the central nervous system, Aprepitant inhibits the emetogenic effects of substance P and enhances the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids, producing a synergistic effect against both the acute and delayed phases of chemotherapy-induced nausea and vomiting.

Pharmacokinetics

• Absorption: Oral bioavailability is variable; peak plasma concentration is reached in about 4 hours.
• Metabolism: Extensively metabolized in the liver, primarily via CYP3A4, with minor contributions from CYP1A2 and CYP2C19. Aprepitant is itself a moderate CYP3A4 inhibitor and inducer, which underlies its significant drug interaction profile (see Drug Interactions).
• Elimination half-life: Approximately 9–13 hours.
• Excretion: Primarily as metabolites in urine and feces; negligible amounts of unchanged drug are excreted in urine.

Take Emestop exactly as directed by the treating physician, timed to the chemotherapy cycle or surgical procedure:

• Swallow capsules whole; they may be taken with or without food.
• For CINV prevention, the first dose is taken about 1 hour before chemotherapy begins; subsequent doses are taken in the morning on the following days, whether or not chemotherapy is given that day.
• For PONV prevention, the single dose is taken within 3 hours before anesthesia is started.
• Oral suspension must be reconstituted by a pharmacist and administered using the provided oral dosing device, not a household spoon.
• Do not use Emestop to treat vomiting or nausea that has already begun; it works only when given ahead of time.

Emestop is a substrate, and a moderate inhibitor and inducer, of the CYP3A4 liver enzyme, which is responsible for most of its clinically significant interactions.

Contraindicated combination

• Pimozide: Emestop inhibits CYP3A4 metabolism of pimozide, raising pimozide levels and increasing the risk of serious or fatal cardiac arrhythmia. Concurrent use is contraindicated (see Contraindications).

Interactions requiring dose adjustment or monitoring

• Warfarin: Emestop can decrease the International Normalized Ratio (INR) and prothrombin time in patients on chronic warfarin therapy. INR should be closely monitored, particularly 7–10 days after each 3-day course of Emestop.
• Corticosteroids (e.g. dexamethasone, methylprednisolone): Emestop increases plasma concentrations of these drugs. Oral dexamethasone dose is typically reduced by about 50% and IV methylprednisolone by about 25% when co-administered with Emestop, per standard antiemetic protocols.
• Hormonal contraceptives: Emestop may reduce the effectiveness of oral contraceptives during the treatment cycle and for 28 days afterward. An alternative or back-up non-hormonal contraceptive method should be used during this period.
• Strong CYP3A4 inhibitors (e.g. ketoconazole): may increase Emestop plasma levels; avoid concurrent use where possible.
• Strong CYP3A4 inducers (e.g. rifampin, carbamazepine, phenytoin): may substantially decrease Emestop plasma levels and effectiveness; avoid concurrent use.
• Other CYP3A4 substrate chemotherapeutic agents (e.g. docetaxel, paclitaxel, etoposide, vinorelbine, ifosfamide, imatinib): Emestop may alter their plasma concentrations; clinical monitoring is advised.

Emestop is generally well tolerated. The most common side effects are fatigue, hiccups, and constipation.

Patients should seek urgent medical attention for signs of a serious allergic reaction (rash, swelling of the face/throat, difficulty breathing) or a severe skin reaction while taking Emestop.

Pregnancy

Animal reproduction studies with Emestop have not shown harm to the fetus at exposures around the human dose, but there are no adequate and well-controlled studies in pregnant women. Emestop should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus. Always consult a physician before use during pregnancy.

Lactation

It is not known whether Emestop passes into human breast milk, though it has been detected in the milk of lactating animals. Because of the potential for adverse effects in a nursing infant, a decision should be made to either discontinue breastfeeding during treatment and for a short period afterward (given the drug's plasma half-life) or to avoid using Emestop, weighing the importance of the medication to the mother. Consult a physician before breastfeeding while using Emestop.

• Emestop is for prevention only — it has not been studied for, and should not be used to treat, nausea and vomiting that has already started.
• Drug interactions: Emestop has clinically significant interactions via CYP3A4 (pimozide, warfarin, corticosteroids, hormonal contraceptives, and other CYP3A4 substrates/inhibitors/inducers) — see Drug Interactions and Contraindications. Always disclose all current medications to the prescribing physician.
• Hepatic impairment: Use with caution in patients with severe hepatic impairment, as clinical data in this population are limited.
• Hypersensitivity reactions: Rare cases of hypersensitivity, including anaphylaxis and angioedema, have been reported; discontinue Emestop immediately if these occur.
• Combination use required for CINV: Emestop must always be used together with a corticosteroid and a 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting prevention — it is not effective as monotherapy for this indication.
• Inform the physician of any planned surgery, as Emestop interacts with certain anesthetic and analgesic drugs metabolized via CYP3A4.

There is no specific antidote for Emestop overdose. Reported overdoses (including doses roughly 11 times the maximum recommended dose) have been associated with drowsiness and headache, without other serious effects reported to date; however, information on overdose remains limited. Emestop is not removed by hemodialysis.

If an overdose is suspected, seek immediate medical attention or contact emergency services / a poison control center. Management should be supportive, with monitoring of vital signs, under medical supervision — do not attempt specific home treatment.

Store Emestop capsules at room temperature (below 30°C), away from light and moisture, in the original packaging. Keep out of reach of children.

Reconstituted oral suspension should be refrigerated (2–8°C) and used within 72 hours, or kept at room temperature for up to 3 hours before use; discard any unused portion after this time.

• Pediatric use: Emestop oral suspension is approved for CINV prevention from 6 months of age; capsules are approved from 12 years of age. Safety and efficacy for PONV prevention have not been established in children. See Pediatric Uses.
• Geriatric use: No dosage adjustment is needed based on age alone; clinical studies have not identified differences in response between elderly and younger patients, though caution is reasonable given a higher likelihood of concomitant disease and other medications.
• Hepatic impairment: No adjustment needed for mild-to-moderate impairment; use with caution in severe impairment due to limited data.
• Renal impairment: No dose adjustment required; not significantly removed by hemodialysis.
• Pregnancy and lactation: See Pregnancy and Lactation for detailed guidance.

Emestop is given as a short, defined course rather than long-term therapy:

• For CINV prevention, a 3-day course is given with each chemotherapy cycle (Day 1 before chemotherapy, plus Days 2 and 3), repeated as needed with subsequent chemotherapy cycles as directed by the oncologist.
• For PONV prevention, a single dose is given before surgery — no further doses are required for that purpose.

Emestop oral suspension is supplied as a powder that must be reconstituted by a pharmacist with the specified amount of water to yield a final concentration of 125 mg/5 mL before dispensing to the patient.

• Shake the reconstituted suspension well before each use.
• Measure each dose precisely using the oral dosing syringe/device provided — do not use a household spoon.
• After reconstitution, store in the refrigerator (2–8°C) and use within 72 hours, or at room temperature for up to 3 hours before administration; discard any unused suspension after this window.

Antiemetics; Neurokinin-1 (NK1) receptor antagonists. Aprepitant is the prototype oral agent in this class.

Aprepitant selectively and with high affinity blocks central substance P/neurokinin-1 (NK1) receptors in the brainstem vomiting centers, with negligible affinity for serotonin (5-HT3), dopamine, or corticosteroid receptors. By preventing substance P from binding to NK1 receptors, Aprepitant suppresses both the acute and delayed phases of chemotherapy- and surgery-induced emesis, and acts synergistically when combined with 5-HT3 receptor antagonists and corticosteroids, which act through separate emetic pathways.

B (legacy FDA pregnancy category; animal studies show no fetal harm at relevant exposures, but adequate human data are lacking)

Emestop oral suspension is approved for the prevention of chemotherapy-induced nausea and vomiting in children as young as 6 months of age, dosed by body weight (3 mg/kg on Day 1, up to a maximum of 125 mg; 2 mg/kg on Days 2 and 3, up to a maximum of 80 mg each day). Capsules are approved for the same indication from 12 years of age, using adult dosing.

The safety and effectiveness of Emestop for prevention of postoperative nausea and vomiting have not been established in pediatric patients, and it should not be used for this purpose in children outside of a physician's specific direction. Neutropenia has been reported more frequently in children than in adults; complete blood counts should be monitored as clinically indicated during chemotherapy courses that include Emestop.