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| {{DrugProjectFormSinglePage
| | #REDIRECT [[Aprepitant]] |
| |authorTag={{AP}}
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| |genericName=Aprepitant
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| |aOrAn=an
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| |drugClass=[[antiemetic]], [[neurokinin-1 receptor antagonist]]
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| |indicationType=prophylaxis
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| |indication=in combination with other antiemetic agents for the:
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| *acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin
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| *of [[nausea]] and [[vomiting]] associated with initial and repeat courses of moderately emetogenic cancer [[chemotherapy]] (MEC)
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| Also, indicated for the prevention of postoperative nausea and vomiting (PONV)
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| |adverseReactions=[[alopecia]], [[anorexia]], [[asthenia]]/[[fatigue]], [[constipation]], [[diarrhea]], [[headache]], [[hiccups]], [[nausea]], [[hypotension]], [[pruritus]], [[pyrexia]]
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| |blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b>
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| |blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
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| |fdaLIADAdult======Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)=====
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| 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.
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| *EMEND may be taken with or without food.
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| *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.
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| In clinical studies with EMEND, the following regimen was used for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy:
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| [[file:Aprepitant Dosage1.png|none|300px]]
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| In a clinical study with EMEND, the following regimen was used for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy:
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| [[file:Aprepitant Dosage2.png|none|300px]] | |
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| =====Prevention of Postoperative Nausea and Vomiting (PONV)=====
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| 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.
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| |offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Aprepitant (patient information) in adult patients.
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| |offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Aprepitant (patient information) in adult patients.
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| |offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Aprepitant (patient information) in pediatric patients.
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| |offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Aprepitant (patient information) in pediatric patients.
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| |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.
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| |warnings======CYP3A4 Interactions=====
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| *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.
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| *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.
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| *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.
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| *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.
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| *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.
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| *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.
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| =====Coadministration with Warfarin (a CYP2C9 substrate)=====
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| 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]].
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| =====Coadministration with Hormonal Contraceptives=====
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| 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.
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| =====Patients with Severe Hepatic Impairment=====
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| 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.
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| =====Chronic Continuous Use=====
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| 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.
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| |clinicalTrials=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.
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| 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%.
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| [[file:Aprepitant AR1.png|none|400px]]
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| In a combined analysis of these two studies, isolated cases of serious adverse experiences were similar in the two treatment groups.
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| Highly and Moderately Emetogenic Chemotherapy
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| 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:
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| Infections and infestations: candidiasis, herpes simplex, lower respiratory infection, oral candidiasis, pharyngitis, septic shock, upper respiratory infection, urinary tract infection.
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| Neoplasms benign, malignant and unspecified (including cysts and polyps): malignant neoplasm, non-small cell lung carcinoma.
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| Blood and lymphatic system disorders: anemia, febrile neutropenia, thrombocytopenia.
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| Metabolism and nutrition disorders: appetite decreased, diabetes mellitus, hypokalemia.
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| Psychiatric disorders: anxiety disorder, confusion, depression.
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| Nervous system: peripheral neuropathy, sensory neuropathy, taste disturbance, tremor.
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| Eye disorders: conjunctivitis.
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| Cardiac disorders: myocardial infarction, palpitations, tachycardia.
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| Vascular disorders: deep venous thrombosis, flushing, hot flush, hypertension, hypotension.
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| Respiratory, thoracic and mediastinal disorders: cough, dyspnea, nasal secretion, pharyngolaryngeal pain, pneumonitis, pulmonary embolism, respiratory insufficiency, vocal disturbance.
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| Gastrointestinal disorders: abdominal pain upper, acid reflux, deglutition disorder, dry mouth, dysgeusia, dysphagia, eructation, flatulence, obstipation, salivation increased.
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| Skin and subcutaneous tissue disorders: acne, diaphoresis, pruritus, rash.
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| Musculoskeletal and connective tissue disorders: arthralgia, back pain, muscular weakness, musculoskeletal pain, myalgia.
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| Renal and urinary disorders: dysuria, renal insufficiency.
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| Reproductive system and breast disorders: pelvic pain.
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| General disorders and administrative site conditions: edema, malaise, pain, rigors.
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| Investigations: weight loss.
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| Stevens-Johnson syndrome was reported as a serious adverse experience in a patient receiving aprepitant with cancer chemotherapy in another CINV study.
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| Laboratory Adverse Experiences
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| Table 3 shows the percent of patients with laboratory adverse experiences reported at an incidence ≥3% in patients receiving highly emetogenic chemotherapy.
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| [[file:Aprepitant AR2.png|none|400px]]
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| 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.
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| 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.
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| Postoperative Nausea and Vomiting
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| 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.
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| 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.
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| [[file:Aprepitant AR3.png||none|400px]]
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| The following additional clinical adverse experiences (incidence >0.5% and greater than ondansetron), regardless of causality, were reported in patients treated with aprepitant:
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| Infections and infestations: postoperative infection
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| Metabolism and nutrition disorders: hypokalemia, hypovolemia.
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| Nervous system disorders: dizziness, hypoesthesia, syncope.
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| Vascular disorders: hematoma
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| Respiratory, thoracic and mediastinal disorders: dyspnea, hypoxia, respiratory depression.
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| Gastrointestinal disorders: abdominal pain, abdominal pain upper, dry mouth, dyspepsia.
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| Skin and subcutaneous tissue disorders: urticaria
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| General disorders and administrative site conditions: hypothermia, pain.
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| Investigations: blood pressure decreased
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| Injury, poisoning and procedural complications: operative hemorrhage, wound dehiscence.
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| Other adverse experiences (incidence ≤0.5%) reported in patients treated with aprepitant 40 mg for postoperative nausea and vomiting included:
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| Nervous system disorders: dysarthria, sensory disturbance.
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| Eye disorders: miosis, visual acuity reduced.
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| Respiratory, thoracic and mediastinal disorders: wheezing
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| Gastrointestinal disorders: bowel sounds abnormal, stomach discomfort.
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| There were no serious adverse drug-related experiences reported in the postoperative nausea and vomiting clinical studies in patients taking 40 mg aprepitant.
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| Laboratory Adverse Experiences
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| One laboratory adverse experience, hemoglobin decreased (40 mg aprepitant 3.8%, ondansetron 4.2%), was reported at an incidence ≥3% in a patient receiving general anesthesia.
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| The following additional laboratory adverse experiences (incidence >0.5% and greater than ondansetron), regardless of causality, were reported in patients treated with aprepitant 40 mg: blood albumin decreased, blood bilirubin increased, blood glucose increased, blood potassium decreased, glucose urine present.
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| The adverse experience of ALT increased occurred with similar incidence in patients treated with aprepitant 40 mg (1.1%) as in patients treated with ondansetron 4 mg (1.0%).
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| Other Studies
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| In addition, two serious adverse experiences were reported in postoperative nausea and vomiting (PONV) clinical studies in patients taking a higher dose of aprepitant: one case of constipation, and one case of sub-ileus.
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| Angioedema and urticaria were reported as serious adverse experiences in a patient receiving aprepitant in a non-CINV/non-PONV study.
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| |postmarketing=The following adverse reactions have been identified during postmarketing use of aprepitant. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to the drug.
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| Skin and subcutaneous tissue disorders: pruritus, rash, urticaria.
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| Immune system disorders: hypersensitivity reactions including anaphylactic reactions.
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| |drugInteractions=====Effect of Aprepitant on the Pharmacokinetics of Other Agents====
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| =====CYP3A4 Substrates=====
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| *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. However, higher aprepitant doses or repeated dosing at any aprepitant dose may have a clinically significant effect.
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| *As a moderate inhibitor of CYP3A4 at a dose of 125 mg/80 mg, aprepitant can increase plasma concentrations of concomitantly administered oral medications that are metabolized through CYP3A4 [see CONTRAINDICATIONS (4)]. The use of fosaprepitant may increase CYP3A4 substrate plasma concentrations to a lesser degree than the use of oral aprepitant (125 mg).
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| *5-HT3 antagonists: In clinical drug interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of dolasetron).
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| *Corticosteroids:
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| **Dexamethasone: EMEND, when given as a regimen of 125 mg with dexamethasone coadministered orally as 20 mg on Day 1, and EMEND when given as 80 mg/day with dexamethasone coadministered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a CYP3A4 substrate, by 2.2-fold on Days 1 and 5. The oral dexamethasone doses should be reduced by approximately 50% when coadministered with EMEND (125 mg/80 mg regimen), to achieve exposures of dexamethasone similar to those obtained when it is given without EMEND. The daily dose of dexamethasone administered in clinical chemotherapy induced nausea and vomiting studies with EMEND reflects an approximate 50% reduction of the dose of dexamethasone [see DOSAGE AND ADMINISTRATION (2.1)]. A single dose of EMEND (40 mg) when coadministered with a single oral dose of dexamethasone 20 mg, increased the AUC of dexamethasone by 1.45-fold. Therefore, no dose adjustment is recommended.
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| **Methylprednisolone: EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of methylprednisolone, a CYP3A4 substrate, by 1.34-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was coadministered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3. The IV methylprednisolone dose should be reduced by approximately 25%, and the oral methylprednisolone dose should be reduced by approximately 50% when coadministered with EMEND (125 mg/80 mg regimen) to achieve exposures of methylprednisolone similar to those obtained when it is given without EMEND. Although the concomitant administration of methylprednisolone with the single 40 mg dose of aprepitant has not been studied, a single 40 mg dose of EMEND produces a weak inhibition of CYP3A4 (based on midazolam interaction study) and it is not expected to alter the plasma concentrations of methylprednisolone to a clinically significant degree. Therefore, no dose adjustment is recommended.
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| Chemotherapeutic agents: [see WARNINGS AND PRECAUTIONS (5.1)]
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| Docetaxel: In a pharmacokinetic study, EMEND (125 mg/80 mg regimen) did not influence the pharmacokinetics of docetaxel.
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| Vinorelbine: In a pharmacokinetic study, EMEND (125 mg/80 mg regimen) did not influence the pharmacokinetics of vinorelbine to a clinically significant degree.
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| CYP2C9 Substrates (Warfarin, Tolbutamide):
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| Aprepitant has been shown to induce the metabolism of S(-) warfarin and tolbutamide, which are metabolized through CYP2C9. Coadministration of EMEND with these drugs or other drugs that are known to be metabolized by CYP2C9, such as phenytoin, may result in lower plasma concentrations of these drugs.
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| Warfarin: A single 125-mg dose of EMEND was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilized on chronic warfarin therapy. Although there was no effect of EMEND on the plasma AUC of R(+) or S(-) warfarin determined on Day 3, there was a 34% decrease in S(-) warfarin (a CYP2C9 substrate) trough concentration accompanied by a 14% decrease in the prothrombin time (reported as International Normalized Ratio or INR) 5 days after completion of dosing with EMEND. In patients on chronic warfarin therapy, the prothrombin time (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.
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| Tolbutamide: EMEND, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 23% on Day 4, 28% on Day 8, and 15% on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15.
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| EMEND, when given as a 40-mg single oral dose on Day 1, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 8% on Day 2, 16% on Day 4, 15% on Day 8, and 10% on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of EMEND 40 mg and on Days 2, 4, 8, and 15. This effect was not considered clinically important.
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| Oral contraceptives: Aprepitant, when given once daily for 14 days as a 100-mg capsule with an oral contraceptive containing 35 mcg of ethinyl estradiol and 1 mg of norethindrone, decreased the AUC of ethinyl estradiol by 43%, and decreased the AUC of norethindrone by 8%.
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| In another study, a daily dose of an oral contraceptive containing ethinyl estradiol and norethindrone was administered on Days 1 through 21, and EMEND was given as a 3-day regimen of 125 mg on Day 8 and 80 mg/day on Days 9 and 10 with ondansetron 32 mg IV on Day 8 and oral dexamethasone given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. In the study, the AUC of ethinyl estradiol decreased by 19% on Day 10 and there was as much as a 64% decrease in ethinyl estradiol trough concentrations during Days 9 through 21. While there was no effect of EMEND on the AUC of norethindrone on Day 10, there was as much as a 60% decrease in norethindrone trough concentrations during Days 9 through 21.
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| In another study, a daily dose of an oral contraceptive containing ethinyl estradiol and norgestimate (which is converted to norelgestromin) was administered on Days 1 through 21, and EMEND 40 mg was given on Day 8. In the study, the AUC of ethinyl estradiol decreased by 4% and 29% on Day 8 and Day 12, respectively, while the AUC of norelgestromin increased by 18% on Day 8 and decreased by 10% on Day 12. In addition, the trough concentrations of ethinyl estradiol and norelgestromin on Days 8 through 21 were generally lower following coadministration of the oral contraceptive with EMEND 40 mg on Day 8 compared to the trough levels following administration of the oral contraceptive alone.
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| The coadministration of EMEND may reduce the efficacy of hormonal contraceptives (these can include birth control pills, skin patches, implants, and certain IUDs) during and for 28 days after administration of the last dose of EMEND. Alternative or back-up methods of contraception should be used during treatment with EMEND and for 1 month following the last dose of EMEND.
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| Midazolam: EMEND increased the AUC of midazolam, a sensitive CYP3A4 substrate, by 2.3-fold on Day 1 and 3.3-fold on Day 5, when a single oral dose of midazolam 2 mg was coadministered on Day 1 and Day 5 of a regimen of EMEND 125 mg on Day 1 and 80 mg/day on Days 2 through 5. The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) should be considered when coadministering these agents with EMEND (125 mg/80 mg). A single dose of EMEND (40 mg) increased the AUC of midazolam by 1.2-fold on Day 1, when a single oral dose of midazolam 2 mg was coadministered on Day 1 with EMEND 40 mg; this effect was not considered clinically important.
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| In another study with intravenous administration of midazolam, EMEND was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, and midazolam 2 mg IV was given prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15. EMEND increased the AUC of midazolam by 25% on Day 4 and decreased the AUC of midazolam by 19% on Day 8 relative to the dosing of EMEND on Days 1 through 3. These effects were not considered clinically important. The AUC of midazolam on Day 15 was similar to that observed at baseline.
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| An additional study was completed with intravenous administration of midazolam and EMEND. Intravenous midazolam 2 mg was given 1 hour after oral administration of a single dose of EMEND 125 mg. The plasma AUC of midazolam was increased by 1.5-fold. Depending on clinical situations (e.g., elderly patients) and degree of monitoring available, dosage adjustment for intravenous midazolam may be necessary when it is coadministered with EMEND for the chemotherapy induced nausea and vomiting indication (125 mg on Day 1 followed by 80 mg on Days 2 and 3).
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| 7.2 Effect of Other Agents on the Pharmacokinetics of Aprepitant
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| Aprepitant is a substrate for CYP3A4; therefore, coadministration of EMEND with drugs that inhibit CYP3A4 activity may result in increased plasma concentrations of aprepitant. Consequently, concomitant administration of EMEND with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) should be approached with caution. Because moderate CYP3A4 inhibitors (e.g., diltiazem) result in a 2-fold increase in plasma concentrations of aprepitant, concomitant administration should also be approached with caution.
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| Aprepitant is a substrate for CYP3A4; therefore, coadministration of EMEND with drugs that strongly induce CYP3A4 activity (e.g., rifampin, carbamazepine, phenytoin) may result in reduced plasma concentrations of aprepitant that may result in decreased efficacy of EMEND.
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| Ketoconazole: When a single 125-mg dose of EMEND was administered on Day 5 of a 10-day regimen of 400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold. Concomitant administration of EMEND with strong CYP3A4 inhibitors should be approached cautiously.
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| Rifampin: When a single 375-mg dose of EMEND was administered on Day 9 of a 14-day regimen of 600 mg/day of rifampin, a strong CYP3A4 inducer, the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased approximately 3-fold.
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| Coadministration of EMEND with drugs that induce CYP3A4 activity may result in reduced plasma concentrations and decreased efficacy of EMEND.
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| 7.3 Additional Interactions
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| EMEND is unlikely to interact with drugs that are substrates for the P-glycoprotein transporter, as demonstrated by the lack of interaction of EMEND with digoxin in a clinical drug interaction study.
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| Diltiazem: In patients with mild to moderate hypertension, administration of aprepitant once daily, as a tablet formulation comparable to 230 mg of the capsule formulation, with diltiazem 120 mg 3 times daily for 5 days, resulted in a 2-fold increase of aprepitant AUC and a simultaneous 1.7-fold increase of diltiazem AUC. These pharmacokinetic effects did not result in clinically meaningful changes in ECG, heart rate or blood pressure beyond those changes induced by diltiazem alone.
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| Paroxetine: Coadministration of once daily doses of aprepitant, as a tablet formulation comparable to 85 mg or 170 mg of the capsule formulation, with paroxetine 20 mg once daily, resulted in a decrease in AUC by approximately 25% and Cmax by approximately 20% of both aprepitant and paroxetine.
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| |alcohol=Alcohol-Aprepitant (patient information) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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| }}
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| {{drug header}}
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| ==Why this medication is prescribed==
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| 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.
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| ==How this medication should be used==
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| 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.
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| 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.
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| Aprepitant only works to prevent upset stomach and vomiting. If you already have these symptoms, do not take aprepitant. Call your doctor instead.
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| 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.
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| ==Other uses for this medicine==
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| This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
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| ==Special precautions==
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| '''Before taking aprepitant:'''
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| *tell your doctor and pharmacist if you are allergic to aprepitant or any other medications.
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| *do not take aprepitant if you are taking astemizole (Hismanal), cisapride (Propulsid), pimozide (Orap), or terfenadine (Seldane).
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| *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.
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| *tell your doctor what herbal products you are taking, especially St. John's Wort.
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| *tell your doctor if you have or have ever had liver disease.
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| *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.
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| ==Special dietary instructions==
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| Talk to your doctor about drinking grapefruit juice while taking this medicine.
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| ==What to do if you forget a dose==
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| 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.
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| ==Side Effects==
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| ===Minor Side Effects===
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| Aprepitant may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
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| *weakness
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| *extreme tiredness
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| *dizziness
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| *diarrhea
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| *constipation
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| *stomach pain
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| *upset stomach
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| *hiccups
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| *loss of appetite
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| ===Severe Side Effects===
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| Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately:
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| *hives
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| *skin rash
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| *difficulty breathing or swallowing
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| *swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
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| *hoarseness
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| 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.
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| Aprepitant may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
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| 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].
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| ==Storage conditions needed for this medication==
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| 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.
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| ==In case of emergency/overdose==
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| 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.
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| '''Symptoms of overdose may include:'''
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| *drowsiness
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| *headache
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| ==Other information==
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| Keep all appointments with your doctor.
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| Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
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| ==Brand names==
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| *Emend®
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|
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| [[Category:Oncology Drugs]]
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| [[Category:Gastrointestinal Drugs]]
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