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penal complex [30:<12 years (and 6 kg) and patients (any age and 6 kg) unable to swallow capsules: Oral: 3 mg/kg (maximum: 125 mg/dose) 1 hour prior to chemotherapy on day 1, followed by 2 mg/kg (maximum: 80 mg/dose) once daily on days 2 and 3 (in combination with a 5-HT 3 antagonist antiemetic on day 1 and dexamethasone on days 1 to 4 [reduce dexamethasone dose to 50% of recommended dose]) Prevention of nausea and vomiting associated with moderately-emetogenic chemotherapy: Capsules: Children 12 years, and Adolescents: Oral: 125 mg 1 hour prior to chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3 (in combination with a 5-HT 3 antagonist antiemetic and dexamethasone on day 1 [reduce dexamethasone dose to 50% of recommended dose]) Suspension: Infants 6 months (and 6 kg), Children> <12 years (and 6 kg) and patients (any age and 6 kg) unable to swallow capsules: Oral: 3 mg/kg (maximum: 125 mg/dose) 1 hour prior to chemotherapy on day 1, followed by 2 mg/kg (maximum: 80 mg/dose) once daily on days 2 and 3 (in combination with a 5-HT 3 antagonist antiemetic and dexamethasone on day 1 [reduce dexamethasone dose to 50% of recommended dose]) Pediatric Oncology Group of Ontario (POGO) guidelines: Recommended antiemetic regimen combinations in pediatric patients 6 months receiving chemotherapy agents that do not potentially interact with aprepitant (Dupuis 2013; Patel 2017): High emetogenic risk: Aprepitant, plus ondansetron or granisetron or palonosetron, plus dexamethasone. High emetogenic risk and cannot receive corticosteroids (due to contraindications): Aprepitant plus palonosetron. Moderate emetogenic risk and cannot receive corticosteroids (due to contraindications): Aprepitant plus ondansetron or granisetron or palonosetron. Infants 6 months, Children, and Adolescents: Oral: 3 mg/kg (maximum dose: 125 mg) on day 1 prior to chemotherapy, followed by 2 mg/kg (maximum dose: 80 mg) once daily on days 2 and 3. Dosing: Renal Impairment No dosage adjustment necessary. ESRD undergoing dialysis: No dosage adjustment necessary. Aprepitant is not removed by hemodialysis. Dosing: Hepatic Impairment Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary. Severe impairment (Child-Pugh class C): Use with caution; no data available; may require additional monitoring for adverse reactions. Reconstitution Suspension: Aprepitant for oral suspension is packaged as a kit, with a 1 mL and a 5 mL oral dosing dispenser, one cap, one mixing cup, and the aprepitant pouch. Fill mixing cup with room temperature drinking water, using the 5 mL dosing dispenser, measure 4.6 mL of water from the mixing cup and discard unused water from cup. Make sure no air is in the dispenser. Add the 4.6 mL water back to the empty cup. Shake content of aprepitant pouch to bottom of pouch and pour entire contents of pouch into mixing cup, add lid and snap shut. Mix suspension by gently swirling 20 times, then gently invert cup 5 times (to avoid foaming, do not shake vigorously). This results in a 25 mg/mL cloudy pink to light pink suspension. If clumps are present, repeat mixing by gently swirling 20 times and gently inverting 5 times. If foam is present, wait for foam to disappear. Measure calculated dose into oral dosing dispenser (use the 1 mL dispenser if dose is 1 mL and the 5 mL dispenser if dose is> 1 mL). If dose is <1 mL, round to nearest 0.1 mL; if dose is> 1 mL, round to the nearest 0.2 mL. Make sure all air is removed from dispenser and dispenser contains the prescribed dose. Place cap on dispenser until it clicks. Discard mixing cup and any suspension remaining in cup. Refer to manufacturer's instructions for further preparation details. Extemporaneously Prepared A suspension for oral administration is commercially available. A 20 mg/mL oral aprepitant suspension may be prepared with capsules and a 1:1 combination of Ora-Sweet and Ora-Plus (or Ora-Blend). Empty the contents of four 125 mg capsules into a mortar and reduce to a fine powder (process will take 10-15 minutes). Add small portions of vehicle and mix to a uniform paste. Add sufficient vehicle to form a liquid; transfer to a graduated cylinder, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 25 mL. Label "shake well" and "refrigerate". Stable for 90 days refrigerated. Dupuis LL, Lingertat-Walsh K, and Walker SE, "Stability of an Extemporaneous Oral Liquid Aprepitant Formulation," Support Care Cancer , 2009, 17(6):701-6.19043742 Administration Capsules: Swallow whole. Prevention of chemotherapy-induced nausea/vomiting: Administer with or without food. First dose should be given 1 hour prior to chemotherapy; subsequent doses should be given 1 hour prior to chemotherapy or in the morning (if no chemotherapy is administered on days 2 and 3). Oral suspension: Dose should be prepared by a health care provider and dispensed to patient or caregiver in an oral dispenser. Administer by placing the dispenser in the patient's mouth along the inner cheek and slowly dispensing the medicine. Prevention of postoperative nausea/vomiting: Administer within 3 hours prior to induction; follow health care provider instructions about food/drink restrictions prior to surgery. Storage Capsules: Store at room temperature of 20 C to 25 C (68 F to 77 F). Oral suspension: Store unopened pouch at 20 C to 25 C (68 F to 77 F); excursions permitted between 15 C to 30 C (59 F to 86 F). Store in the original container. Do not open pouch until ready to use. Once prepared, if suspension is not used immediately, store refrigerated (between [2 C to 8 C/36 F to 46 F]) for up to 72 hours. When ready to use, the mixture may be kept at room temperature (between [20 C to 25 C/68 F to 77 F]) for up to 3 hours. Drug Interactions Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Monitor therapy Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Consider therapy modification AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Monitor therapy Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Monitor therapy ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy Astemizole: Aprepitant may increase the serum concentration of Astemizole. Avoid combination Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Avoid combination Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects. Consider therapy modification Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Monitor therapy Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Monitor therapy Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Consider therapy modification Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Avoid combination Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Consider therapy modification Cisapride: Aprepitant may increase the serum concentration of Cisapride. Avoid combination Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily. Avoid combination Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination Corticosteroids (Systemic): Aprepitant may increase the serum concentration of Corticosteroids (Systemic). Management: No dose adjustment is needed for single 40 mg aprepitant doses. For other regimens, reduce oral dexamethasone or methylprednisolone doses by 50%, and IV methylprednisolone doses by 25%. Antiemetic regimens containing dexamethasone reflect this adjustment. Consider therapy modification CYP2C9 Substrates (High risk with Inducers): CYP2C9 Inducers (Strong) may increase the metabolism of CYP2C9 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy CYP3A4 Inducers (Strong): May decrease the serum concentration of Aprepitant. Avoid combination CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Aprepitant. Avoid combination CYP3A4 Inhibitors (Strong): May increase the serum concentration of Aprepitant. Avoid combination CYP3A4 Substrates (High risk with Inhibitors): Aprepitant may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Consider therapy modification Dasatinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Consider therapy modification Diclofenac (Systemic): CYP2C9 Inducers (Strong) may decrease the serum concentration of Diclofenac (Systemic). Monitor therapy Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Monitor therapy Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Avoid combination DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Consider therapy modification Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details. Consider therapy modification Estrogen Derivatives (Contraceptive): Aprepitant may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use of a non-hormone-based contraceptive is recommended. Consider therapy modification Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Avoid combination Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Consider therapy modification Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Management: Extreme caution, with possibly increased monitoring of cardiac status (eg, ECG), should be used with concurrent use of halofantrine with any moderate CYP3A4 inhibitor(s). Consider therapy modification HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Monitor therapy HydrOXYzine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HydrOXYzine. Management: This combination is specifically contraindicated in some non-U.S. labeling. Consider therapy modification Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 140 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Consider therapy modification Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination Ifosfamide: Aprepitant may increase the serum concentration of Ifosfamide. Specifically, concentrations of the toxic metabolites of ifosfamide may increase. Monitor therapy Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full monograph content for specific age- and weight-based recommendations. No dose adjustment is needed when using ivacaftor/lumacaftor with a moderate CYP3A4 inhibitor. Consider therapy modification Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: Lurasidone US labeling recommends reducing lurasidone dose by half with a moderate CYP3A4 inhibitor. Some non-US labeling recommends initiating lurasidone at 20 mg/day and limiting dose to 40 mg/day; avoid concurrent use of grapefruit products. Consider therapy modification Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Monitor therapy Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Monitor therapy Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Monitor therapy Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Monitor therapy Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Avoid combination Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Avoid combination NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Monitor therapy Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 200 mg twice daily. Avoid combination OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Monitor therapy Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy PARoxetine: May decrease the serum concentration of Aprepitant. Aprepitant may decrease the serum concentration of PARoxetine. Monitor therapy Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Monitor therapy Pimozide: Aprepitant may increase the serum concentration of Pimozide. Avoid combination Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification Progestins (Contraceptive): Aprepitant may decrease the serum concentration of Progestins (Contraceptive). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Monitor therapy Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Consider therapy modification Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Monitor therapy Ruxolitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib. Monitor therapy Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Monitor therapy Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Monitor therapy Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Monitor therapy Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination Sirolimus: Aprepitant may increase the serum concentration of Sirolimus. Monitor therapy Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Consider therapy modification St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Consider therapy modification Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Monitor therapy Terfenadine: Aprepitant may increase the serum concentration of Terfenadine. Avoid combination Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Monitor therapy Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy TOLBUTamide: Aprepitant may decrease the serum concentration of TOLBUTamide. Monitor therapy Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Avoid combination Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Monitor therapy Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Monitor therapy Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Monitor therapy Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Monitor therapy Warfarin: Aprepitant may decrease the serum concentration of Warfarin. Monitor therapy Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Monitor therapy Adverse Reactions Adverse reactions may be reported in combination with other antiemetic agents. As reported for highly emetogenic cancer chemotherapy or moderately emetogenic cancer chemotherapy, unless otherwise noted as reported for postoperative nausea and vomiting (PONV). >10%: Central nervous system: Fatigue (adults: 13%; children & adolescents: 5%) Hematologic & oncologic: Neutropenia (children & adolescents: 13%; adults: <3%) 0.5% to 10%: Cardiovascular: Hypotension (PONV: 6%), bradycardia (PONV:> <3%), flushing (> <3%), palpitations (> <3%), peripheral edema (> <3%), syncope (PONV:> <3%) Central nervous system: Headache (children & adolescents: 9%), dizziness (> <3% to 5%), anxiety (> <3%), hypoesthesia (PONV:> <3%), hypothermia (PONV:> <3%), malaise (> <3%), peripheral neuropathy (> <3%), abnormal behavior (children & adolescents: 2%), agitation (children & adolescents: 2%) Dermatologic: Alopecia (> <3%), hyperhidrosis (> <3%), skin rash (> <3%), urticaria (> <3%) Endocrine & metabolic: Dehydration ( 3%), decreased serum albumin (PONV:> <3%), decreased serum potassium (PONV:> <3%), decreased serum sodium (> <3%), hot flash (> <3), hypokalemia (> <3%), hypovolemia (PONV:> <3%), increased serum glucose (PONV:> <3%), weight loss (> <3%) Gastrointestinal: Constipation (PONV: 9%), diarrhea (6% to 9%), dyspepsia ( 7%), abdominal pain ( 6%), hiccups (4% to 5%), decreased appetite (> <3% to 5%), dysgeusia (> <3%), eructation (> <3%), flatulence (> <3%), gastritis (> <3%), gastroesophageal reflux disease (> <3%), nausea (> <3%), vomiting (> <3%), xerostomia (> <3%) Genitourinary: Proteinuria (> <3%) Hematologic & oncologic: Decreased hemoglobin (children & adolescents: 5%), decreased white blood cell count ( 4%), anemia (> <3%), febrile neutropenia (> <3%), hematoma (PONV:> <3%), thrombocytopenia (> <3%) Hepatic: Increased serum ALT (3%), increased serum alkaline phosphatase (> <3%), increased serum AST (> <3%), increased serum bilirubin (PONV:> <3%) Infection: Candidiasis (> <3%), postoperative infection (PONV:> <3%) Neuromuscular & skeletal: Weakness ( 7%), musculoskeletal pain (> <3%) Renal: Increased blood urea nitrogen (> <3%) Respiratory: Cough (> <3% to 5%), dyspnea (> <3%), hypoxia (PONV:> <3%), oropharyngeal pain (> <3%), pharyngitis (> <3%), respiratory depression (PONV:> <3%) Miscellaneous: Wound dehiscence (PONV:> <3%)> <0.5% (Limited to important or life-threatening): Anaphylaxis, angioedema, hypersensitivity reaction, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis Warnings/Precautions Concerns related to adverse effects: Hypersensitivity: Hypersensitivity reactions, including anaphylactic reactions have been reported. Disease-related concerns: Hepatic impairment: Use with caution in patients with severe hepatic impairment (Child-Pugh class C); has not been studied. Concurrent drug therapy issues: Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Due to a risk of significantly increased pimozide plasma concentrations and potential for QT prolongation, concurrent use with pimozide is contraindicated. Other CYP3A4-mediated drug interactions may occur. In patients receiving concurrent warfarin, a clinically significant decrease in INR or prothrombin time (PT) may occur; monitor INR/PT for 2 weeks (particularly at 7 to 10 days) following aprepitant administration. Special populations: Pediatrics: For prevention of chemotherapy-induced nausea and vomiting, use is not recommended in pediatric patients weighing> <6 kg. Not approved for prevention of postoperative nausea and vomiting in children. Monitoring Parameters In patients large


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