APREPITANT Drug Interactions: What You Need to Know
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Drug Interactions (FDA Label)
INTERACTIONS See Full Prescribing Information for a list of clinically significant drug interactions. ( 4 , 5.1 , 5.2 , 5.3 , 7.1 , 7.2 )
7.1 Effect of Aprepitant on the Pharmacokinetics of Other Drugs Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Aprepitant acts as a moderate inhibitor of CYP3A4 when administered as a 3-day regimen (125mg/80-mg/80-mg) and can increase plasma concentrations of concomitant drugs that are substrates for CYP3A4. Aprepitant acts as a weak inhibitor when administered as a single 40-mg dose and has not been shown to alter the plasma concentrations of concomitant drugs that are primarily metabolized through CYP3A4. Some substrates of CYP3A4 are contraindicated with aprepitant <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> . Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 10.
Table
10: Effects of Aprepitant on the Pharmacokinetics of Other Drugs CYP3A4 Substrates Pimozide Clinical Impact Increased pimozide exposure Intervention Aprepitant is contraindicated [see Contraindications ( 4 )] .
Benzodiazepines Clinical Impact
Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology ( 12.3 )].
Intervention
3-day aprepitant regimen Monitor for benzodiazepine-related adverse reactions. Depending on the clinical situation (e.g., elderly patients) and degree of monitoring available, reduce the dose of intravenous midazolam Single 40 mg dose of aprepitant No dosage adjustment of the benzodiazepine needed Dexamethasone Clinical Impact Increased dexamethasone exposure [see Clinical Pharmacology ( 12.3 )].
Intervention
3-day aprepitant regimen Reduce the dose of oral dexamethasone by approximately 50% [see Dosage and Administration ( 2.1 )].
Single
40 mg dose of aprepitant No dosage adjustment of oral dexamethasone needed Methylprednisolone Clinical Impact Increased methylprednisolone exposure [see Clinical Pharmacology ( 12.3 )].
Intervention
3-day aprepitant regimen Reduce the dose of intravenous methylprednisolone by approximately 25% Reduce the dose of oral methylprednisolone by approximately 50% Single 40 mg dose of aprepitant No dosage adjustment of methylprednisolone needed Chemotherapeutic agents that are metabolized by CYP3A4 Clinical Impact Increased exposure of the chemotherapeutic agent may increase the risk of adverse reactions [see Clinical Pharmacology ( 12.3 )] .
Intervention
Vinblastine, vincristine, or ifosfamide or other chemotherapeutic agents Monitor for chemotherapeutic-related adverse reactions. Etoposide, vinorelbine, paclitaxel, and docetaxel No dosage adjustment needed.
Hormonal Contraceptives Clinical Impact
Decreased hormonal exposure during administration of and for 28 days after administration of the last dose of aprepitant [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.3 ), Clinical Pharmacology ( 12.3 )] .
Intervention
Effective alternative or back-up methods of contraception (such as condoms and spermicides) should be used during treatment with aprepitant and for 1 month following the last dose of aprepitant. Examples birth control pills, skin patches, implants, and certain IUDs CYP2C9 Substrates Warfarin Clinical Impact Decreased warfarin exposure and decreased prothrombin time (INR) [see Warnings and Precautions ( 5.2 ), Clinical Pharmacology ( 12.3 )] . Intervention In patients on chronic warfarin therapy, monitor the prothrombin time (INR) in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day aprepitant regimen with each chemotherapy cycle, or following administration of a single 40-mg dose of aprepitant.
Other
5-HT 3 Antagonists Clinical Impact No change in the exposure of the 5-HT 3 antagonist [see Clinical Pharmacology ( 12.3 )] . Intervention No dosage adjustment needed Examples ondansetron, granisetron, dolasetron
7.2 Effect of Other Drugs on the Pharmacokinetics of Aprepitant Aprepitant is a CYP3A4 substrate <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Co-administration of aprepitant with drugs that are inhibitors or inducers of CYP3A4 may result in increased or decreased plasma concentrations of aprepitant, respectively, as shown in Table 11.
Table
11: Effects of Other Drugs on Pharmacokinetics of Aprepitant Moderate to Strong CYP3A4 Inhibitors Clinical Impact Significantly increased exposure of aprepitant may increase the risk of adverse reactions associated with aprepitant [see Adverse Reactions ( 6.1 ) and Clinical Pharmacology ( 12.3 )] .
Intervention
Avoid concomitant use of aprepitant Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of aprepitant [see Clinical Pharmacology ( 12.3 )] .
Intervention
Avoid concomitant use of aprepitant Examples rifampin, carbamazepine, phenytoin
7.1 Effect of Aprepitant on the Pharmacokinetics of Other Drugs Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Aprepitant acts as a moderate inhibitor of CYP3A4 when administered as a 3-day regimen (125mg/80-mg/80-mg) and can increase plasma concentrations of concomitant drugs that are substrates for CYP3A4. Aprepitant acts as a weak inhibitor when administered as a single 40-mg dose and has not been shown to alter the plasma concentrations of concomitant drugs that are primarily metabolized through CYP3A4. Some substrates of CYP3A4 are contraindicated with aprepitant <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> . Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 10.
Table
10: Effects of Aprepitant on the Pharmacokinetics of Other Drugs CYP3A4 Substrates Pimozide Clinical Impact Increased pimozide exposure Intervention Aprepitant is contraindicated [see Contraindications ( 4 )] .
Benzodiazepines Clinical Impact
Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology ( 12.3 )].
Intervention
3-day aprepitant regimen Monitor for benzodiazepine-related adverse reactions. Depending on the clinical situation (e.g., elderly patients) and degree of monitoring available, reduce the dose of intravenous midazolam Single 40 mg dose of aprepitant No dosage adjustment of the benzodiazepine needed Dexamethasone Clinical Impact Increased dexamethasone exposure [see Clinical Pharmacology ( 12.3 )].
Intervention
3-day aprepitant regimen Reduce the dose of oral dexamethasone by approximately 50% [see Dosage and Administration ( 2.1 )].
Single
40 mg dose of aprepitant No dosage adjustment of oral dexamethasone needed Methylprednisolone Clinical Impact Increased methylprednisolone exposure [see Clinical Pharmacology ( 12.3 )].
Intervention
3-day aprepitant regimen Reduce the dose of intravenous methylprednisolone by approximately 25% Reduce the dose of oral methylprednisolone by approximately 50% Single 40 mg dose of aprepitant No dosage adjustment of methylprednisolone needed Chemotherapeutic agents that are metabolized by CYP3A4 Clinical Impact Increased exposure of the chemotherapeutic agent may increase the risk of adverse reactions [see Clinical Pharmacology ( 12.3 )] .
Intervention
Vinblastine, vincristine, or ifosfamide or other chemotherapeutic agents Monitor for chemotherapeutic-related adverse reactions. Etoposide, vinorelbine, paclitaxel, and docetaxel No dosage adjustment needed.
Hormonal Contraceptives Clinical Impact
Decreased hormonal exposure during administration of and for 28 days after administration of the last dose of aprepitant [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.3 ), Clinical Pharmacology ( 12.3 )] .
Intervention
Effective alternative or back-up methods of contraception (such as condoms and spermicides) should be used during treatment with aprepitant and for 1 month following the last dose of aprepitant. Examples birth control pills, skin patches, implants, and certain IUDs CYP2C9 Substrates Warfarin Clinical Impact Decreased warfarin exposure and decreased prothrombin time (INR) [see Warnings and Precautions ( 5.2 ), Clinical Pharmacology ( 12.3 )] . Intervention In patients on chronic warfarin therapy, monitor the prothrombin time (INR) in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day aprepitant regimen with each chemotherapy cycle, or following administration of a single 40-mg dose of aprepitant.
Other
5-HT 3 Antagonists Clinical Impact No change in the exposure of the 5-HT 3 antagonist [see Clinical Pharmacology ( 12.3 )] . Intervention No dosage adjustment needed Examples ondansetron, granisetron, dolasetron
7.2 Effect of Other Drugs on the Pharmacokinetics of Aprepitant Aprepitant is a CYP3A4 substrate <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Co-administration of aprepitant with drugs that are inhibitors or inducers of CYP3A4 may result in increased or decreased plasma concentrations of aprepitant, respectively, as shown in Table 11.
Table
11: Effects of Other Drugs on Pharmacokinetics of Aprepitant Moderate to Strong CYP3A4 Inhibitors Clinical Impact Significantly increased exposure of aprepitant may increase the risk of adverse reactions associated with aprepitant [see Adverse Reactions ( 6.1 ) and Clinical Pharmacology ( 12.3 )] .
Intervention
Avoid concomitant use of aprepitant Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of aprepitant [see Clinical Pharmacology ( 12.3 )] .
Intervention
Avoid concomitant use of aprepitant Examples rifampin, carbamazepine, phenytoin
Contraindications
CINVANTI is contraindicated in patients: who are hypersensitive to any component of the product [see Description (11) ] . Hypersensitivity reactions including anaphylaxis have been reported [see Warnings and Precautions (5.2) , Adverse Reactions (6.2) ] . taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of pimozide, which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions (5.1) ] . Known hypersensitivity to any component of this drug. ( 4 , 5.2 ) Concurrent use with pimozide. ( 4 )
Related Warnings
AND PRECAUTIONS
- CYP3A4 Interactions : Aprepitant is a substrate, weak-to-moderate inhibitor and inducer of CYP3A4; See Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustments of aprepitant and concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 )
- Warfarin (a CYP2C9 substrate) : Risk of decreased INR of prothrombin time; monitor INR in 2-week period, particularly at 7 to 10 days, following initiation of aprepitant. ( 5.2 , 7.1 )
- Hormonal Contraceptives : Efficacy of contraceptives may be reduced during administration of and for 28 days following the last dose of aprepitant. Use effective alternative or back-up methods of contraception. ( 5.3 , 7.1 , 8.3 )