Aprepitant (patient information)

Aprepitant (patient information)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Overview

Aprepitant (patient information) is an antiemetic, neurokinin-1 receptor antagonist that is FDA approved for the prophylaxis of in combination with other antiemetic agents for the:

• acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin
• of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)

Also, indicated for the prevention of postoperative nausea and vomiting (PONV). Common adverse reactions include alopecia, anorexia, asthenia/fatigue, constipation, diarrhea, headache, hiccups, nausea, hypotension, pruritus, pyrexia.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

Capsules of EMEND (aprepitant) are given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. The recommended dose of EMEND is 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80 mg orally once daily in the morning on Days 2 and 3.

• EMEND may be taken with or without food.
• EMEND (fosaprepitant dimeglumine) for Injection (115 mg) is a prodrug of aprepitant and may be substituted for oral EMEND (125 mg), 30 minutes prior to chemotherapy, on Day 1 only of the CINV regimen as an intravenous infusion administered over 15 minutes.

In clinical studies with EMEND, the following regimen was used for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy:

In a clinical study with EMEND, the following regimen was used for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy:

Prevention of Postoperative Nausea and Vomiting (PONV)

The recommended oral dosage of EMEND is 40 mg within 3 hours prior to induction of anesthesia. EMEND may be taken with or without food.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Aprepitant (patient information) in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Aprepitant (patient information) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Aprepitant (patient information) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Aprepitant (patient information) in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Aprepitant (patient information) in pediatric patients.

Contraindications

EMEND is contraindicated in patients who are hypersensitive to any component of the product. EMEND is a dose-dependent inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4). EMEND should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

Warnings

CYP3A4 Interactions

• EMEND (aprepitant), a dose-dependent inhibitor of CYP3A4, should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. Moderate inhibition of CYP3A4 by aprepitant, 125 mg/80 mg regimen, could result in elevated plasma concentrations of these concomitant medications.
• Weak inhibition of CYP3A4 by a single 40 mg dose of aprepitant is not expected to alter the plasma concentrations of concomitant medications that are primarily metabolized through CYP3A4 to a clinically significant degree.
• When aprepitant is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND is used concomitantly with medications that induce CYP3A4 activity aprepitant plasma concentrations could be reduced and this may result in decreased efficacy of EMEND.
• Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine and vincristine. In clinical studies, EMEND (125 mg/80 mg regimen) was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions.
• In separate pharmacokinetic studies no clinically significant change in docetaxel or vinorelbine pharmacokinetics was observed when EMEND (125 mg/80 mg regimen) was co-administered.
• Due to the small number of patients in clinical studies who received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied.

Coadministration with Warfarin (a CYP2C9 substrate)

Coadministration of EMEND with warfarin may result in a clinically significant decrease in International Normalized Ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of EMEND with each chemotherapy cycle, or following administration of a single 40 mg dose of EMEND for the prevention of postoperative nausea and vomiting.

Coadministration with Hormonal Contraceptives

Upon coadministration with EMEND, the efficacy of hormonal contraceptives during and for 28 days following the last dose of EMEND may be reduced. Alternative or back-up methods of contraception should be used during treatment with EMEND and for 1 month following the last dose of EMEND.

Patients with Severe Hepatic Impairment

There are no clinical or pharmacokinetic data in patients with severe hepatic impairment ([Child-Pugh score]] >9). Therefore, caution should be exercised when EMEND is administered in these patients.

Chronic Continuous Use

Chronic continuous use of EMEND for prevention of nausea and vomiting is not recommended because it has not been studied; and because the drug interaction profile may change during chronic continuous use.

Adverse Reactions

Clinical Trials Experience

In 2 well-controlled clinical trials in patients receiving highly emetogenic cancer chemotherapy, 544 patients were treated with aprepitant during Cycle 1 of chemotherapy and 413 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy. EMEND was given in combination with ondansetron and dexamethasone. In Cycle 1, clinical adverse experiences were reported in approximately 69% of patients treated with the aprepitant regimen compared with approximately 68% of patients treated with standard therapy. Table 1 shows the percent of patients with clinical adverse experiences reported at an incidence ≥3%.

In a combined analysis of these two studies, isolated cases of serious adverse experiences were similar in the two treatment groups.

Highly and Moderately Emetogenic Chemotherapy

The following additional clinical adverse experiences (incidence >0.5% and greater than standard therapy), regardless of causality, were reported in patients treated with aprepitant regimen in either HEC or MEC studies:

Infections and infestations: candidiasis, herpes simplex, lower respiratory infection, oral candidiasis, pharyngitis, septic shock, upper respiratory infection, urinary tract infection.

Neoplasms benign, malignant and unspecified (including cysts and polyps): malignant neoplasm, non-small cell lung carcinoma.

Blood and lymphatic system disorders: anemia, febrile neutropenia, thrombocytopenia.

Metabolism and nutrition disorders: appetite decreased, diabetes mellitus, hypokalemia.

Psychiatric disorders: anxiety disorder, confusion, depression.

Nervous system: peripheral neuropathy, sensory neuropathy, taste disturbance, tremor.

Eye disorders: conjunctivitis.

Cardiac disorders: myocardial infarction, palpitations, tachycardia.

Vascular disorders: deep venous thrombosis, flushing, hot flush, hypertension, hypotension.

Respiratory, thoracic and mediastinal disorders: cough, dyspnea, nasal secretion, pharyngolaryngeal pain, pneumonitis, pulmonary embolism, respiratory insufficiency, vocal disturbance.

Gastrointestinal disorders: abdominal pain upper, acid reflux, deglutition disorder, dry mouth, dysgeusia, dysphagia, eructation, flatulence, obstipation, salivation increased.

Skin and subcutaneous tissue disorders: acne, diaphoresis, pruritus, rash.

Musculoskeletal and connective tissue disorders: arthralgia, back pain, muscular weakness, musculoskeletal pain, myalgia.

Renal and urinary disorders: dysuria, renal insufficiency.

Reproductive system and breast disorders: pelvic pain.

General disorders and administrative site conditions: edema, malaise, pain, rigors.

Investigations: weight loss.

Stevens-Johnson syndrome was reported as a serious adverse experience in a patient receiving aprepitant with cancer chemotherapy in another CINV study.

Laboratory Adverse Experiences

Table 3 shows the percent of patients with laboratory adverse experiences reported at an incidence ≥3% in patients receiving highly emetogenic chemotherapy.

The following additional laboratory adverse experiences (incidence >0.5% and greater than standard therapy), regardless of causality, were reported in patients treated with aprepitant regimen: alkaline phosphatase increased, hyperglycemia, hyponatremia, leukocytes increased, erythrocyturia, leukocyturia.

The adverse experience profiles in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were generally similar to that observed in Cycle 1.

Postoperative Nausea and Vomiting

In well-controlled clinical studies in patients receiving general anesthesia, 564 patients were administered 40 mg aprepitant orally and 538 patients were administered 4 mg ondansetron IV.

Clinical adverse experiences were reported in approximately 60% of patients treated with 40 mg aprepitant compared with approximately 64% of patients treated with 4 mg ondansetron IV. Table 4 shows the percent of patients with clinical adverse experiences reported at an incidence ≥3% of the combined studies.

Postmarketing Experience

There is limited information regarding Aprepitant (patient information) Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Aprepitant (patient information) Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Aprepitant (patient information) in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Aprepitant (patient information) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Aprepitant (patient information) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Aprepitant (patient information) in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Aprepitant (patient information) in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Aprepitant (patient information) in geriatric settings.

Gender

There is no FDA guidance on the use of Aprepitant (patient information) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Aprepitant (patient information) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Aprepitant (patient information) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Aprepitant (patient information) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Aprepitant (patient information) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Aprepitant (patient information) in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Aprepitant (patient information) Administration in the drug label.

Monitoring

There is limited information regarding Aprepitant (patient information) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Aprepitant (patient information) and IV administrations.

Overdosage

There is limited information regarding Aprepitant (patient information) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Aprepitant (patient information) Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Aprepitant (patient information) Mechanism of Action in the drug label.

Structure

There is limited information regarding Aprepitant (patient information) Structure in the drug label.

Pharmacodynamics

There is limited information regarding Aprepitant (patient information) Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Aprepitant (patient information) Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Aprepitant (patient information) Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Aprepitant (patient information) Clinical Studies in the drug label.

How Supplied

There is limited information regarding Aprepitant (patient information) How Supplied in the drug label.

Storage

There is limited information regarding Aprepitant (patient information) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Aprepitant (patient information) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Aprepitant (patient information) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Aprepitant (patient information) Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Aprepitant (patient information) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Why this medication is prescribed

Aprepitant is used with other medications to prevent upset stomach and vomiting caused by cancer chemotherapy treatment. Aprepitant is in a class of medications called antiemetics. It works by blocking the action of neurokinin, a natural substance in the brain that causes upset stomach and vomiting.

How this medication should be used

Aprepitant comes as a capsule to swallow with a drink. Aprepitant is usually taken once daily, with or without food, during the first few days of your cancer chemotherapy treatment. You will probably take aprepitant 1 hour before your first dose of chemotherapy, and then each morning for the next 2 days. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take aprepitant exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Aprepitant capsules come in two different strengths. Your doctor may prescribe both of the strengths for you to take at different times. You should be careful to take the right strength at the right time as directed by your doctor.

Aprepitant only works to prevent upset stomach and vomiting. If you already have these symptoms, do not take aprepitant. Call your doctor instead.

Aprepitant is used only during the first 3 days of cancer chemotherapy treatment cycles. Do not continue taking aprepitant longer than instructed by your doctor.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Special precautions

Before taking aprepitant:

• tell your doctor and pharmacist if you are allergic to aprepitant or any other medications.
• do not take aprepitant if you are taking astemizole (Hismanal), cisapride (Propulsid), pimozide (Orap), or terfenadine (Seldane).
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking. Be sure to mention any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin); antifungals such as fluconzaole (Diflucan), itraconzaole (Sporanox), and ketoconazole (Nizoral); benzodiazepines such as alprazolam (Xanax), diazepam (Valium), and triazolam (Halcion); buspirone (BuSpar); calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Dilacor, Tiazac,), felodipine (Lexxel, Plendil), nifedipine (Adalat, Procardia), nisoldipine (Sular), and verapamil (Calan, Isoptin, Verelan); chlolesterol-lowering medications (statins) such as atorvastatin (Lipitor), fluvastatin (Lescol); lovastatin (Altocor, Mevacor), and simvastin (Zocor); cancer chemotherapy medications such as docetaxel (Taxotere), etoposide (Toposar, VePesid), ifosfamide (Ifex), imatinib (Gleevec), irinotecan (Camptosar), paclitaxel (Taxol), tamoxifen (Nolvadex), vinblastine, vincristine (Vincasar), and vinorelbine (Navelbine); carbamazepine (Tegretol); celecoxib (Celebrex); chlorpheniramine (Chlor-Trimeton, other cough, cold and sinus medications); cimetidine (Tagamet); clarithromycin (Biaxin); cyclosporine (Neoral, Sandimmune); danazol (Danocrine); delavirdine (Rescriptor); dexamethasone (Decadron); diclofenac (Arthrotec, Voltaren); efavirenz (Sustiva); erythromycin (E.E.S., E-Mycin, Erythrocin); ethosuximide (Zarontin); fluoxetine (Prozac, Sarafem); fluvoxamine (Luvox); glipizide (Glucotrol); haloperidol (Haldol); HIV protease inhibitors such as indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), and saquinavir (Fortovase, Invirase); ibuprofen (Advil, Motrin); irbesartan (Avapro, Avalide); isoniazid (INH, Nydriazid); losartan (Cozaar, Hyzaar); methadone (Dolophine, Methadose); methylprednisolone (Medrol); metronidazole (Flagyl); naproxen ( Naprosyn); nefazadone (Serzone); oral contraceptives (birth control pills); phenobarbital (Luminal, Solfoton); phenytoin (Dilantin); piroxicam (Feldene); quinidine (Cardioglute, Quinaglute); quinine; rifabutin (Mycobutin); rifampin (Rifadin, Rimactane); tacrolimus (Prograf); sildenafil (Viagra); sulfamethoxazole (Bactrim, Septra, Sulfatrim); tolbutamide (Orinase); torsemide (Demadex); trazodone; troleandomycin (TAO); and zafirlukast (Accolate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John's Wort.
• tell your doctor if you have or have ever had liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking aprepitant, call your doctor.

Special dietary instructions

Talk to your doctor about drinking grapefruit juice while taking this medicine.

What to do if you forget a dose

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Side Effects

Minor Side Effects

Aprepitant may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• weakness
• extreme tiredness
• dizziness
• diarrhea
• constipation
• stomach pain
• upset stomach
• hiccups
• loss of appetite

Severe Side Effects

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately:

• hives
• skin rash
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness

Laboratory animals who were given aprepitant developed tumors. It is not known if aprepitant increases the risk of tumors in humans. Talk to your doctor about the risks of taking aprepitant.

Aprepitant may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/MedWatch/report.htm] or by phone [1-800-332-1088].

Storage conditions needed for this medication

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• drowsiness
• headache

Other information

Keep all appointments with your doctor.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

Brand names

• Emend®