|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
|contraindications='''Hypersensitivity'''
=====Body as a Whole=====
* EMEND for Injection is contraindicated in patients who are [[hypersensitive]] to EMEND for Injection, aprepitant, polysorbate 80 or any other components of the product. Known [[hypersensitivity]] reactions include: [[flushing]], [[erythema]], [[dyspnea]], and [[anaphylactic reactions]].
'''Concomitant Use with Pimozide or Cisapride'''
=====Cardiovascular=====
* Aprepitant, when administered orally, is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor following the 3-day antiemetic dosing regimen for CINV. Since fosaprepitant is rapidly converted to aprepitant, do not use fosaprepitant concurrently with pimozide 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'''
* Fosaprepitant is rapidly converted to aprepitant, which is a moderate inhibitor of CYP3A4 when administered as a 3-day antiemetic dosing regimen for CINV. Fosaprepitant should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by aprepitant or fosaprepitant could result in elevated plasma concentrations of these concomitant medications. When fosaprepitant is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When aprepitant is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant.
* Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine and vincristine. In clinical studies, the oral aprepitant 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 the oral aprepitant regimen was coadministered.
=====Digestive=====
* 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 [see DRUG INTERACTIONS (7.1)].
=====Endocrine=====
=====Hematologic and Lymphatic=====
'''Hypersensitivity Reactions'''
* Isolated reports of immediate hypersensitivity reactions including [[flushing]], [[erythema]], [[dyspnea]], and [[anaphylaxis]] have occurred during infusion of fosaprepitant. These [[hypersensitivity]] reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. Reinitiation of the infusion is not recommended in patients who experience these symptoms during first-time use.
'''Coadministration with Warfarin (a CYP2C9 substrate)'''
* Coadministration of fosaprepitant or aprepitant 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 fosaprepitant with each chemotherapy cycle.
=====Metabolic and Nutritional=====
'''Coadministration with Hormonal Contraceptives'''
* Upon coadministration with fosaprepitant or aprepitant, the efficacy of hormonal contraceptives may be reduced during and for 28 days following the last dose of either fosaprepitant or aprepitant. Alternative or back-up methods of contraception should be used during treatment with and for 1 month following the last dose of fosaprepitant or aprepitant.
'''Chronic Continuous Use'''
* Chronic continuous use of EMEND for Injection 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.
|clinicalTrials='''Clinical Trials Experience'''
=====Musculoskeletal=====
* Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
* Since EMEND for Injection is converted to aprepitant, those adverse reactions associated with aprepitant might also be expected to occur with EMEND for Injection.
* The overall safety of fosaprepitant was evaluated in approximately 1100 individuals and the overall safety of aprepitant was evaluated in approximately 6500 individuals.
''Oral Aprepitant''
=====Neurologic=====
''Highly Emetogenic Chemotherapy (HEC)''
* 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. Oral aprepitant was given in combination with ondansetron and [[dexamethasone]].
* In Cycle 1, adverse reactions were reported in approximately 17% of patients treated with the aprepitant regimen compared with approximately 13% of patients treated with standard therapy. Treatment was discontinued due to adverse reactions in 0.6% of patients treated with the aprepitant regimen compared with 0.4% of patients treated with standard therapy.
* The most common adverse reactions reported in patients treated with the aprepitant regimen with an incidence ≥1% and greater than standard therapy are listed in Table 5.
=====Respiratory=====
[[File:Fosaprepitant table5.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
* A listing of adverse reactions in the aprepitant regimen (incidence <1%) that occurred at a greater incidence than standard therapy are presented in the Less Common Adverse Reactions subsection below.
* In an additional active-controlled clinical study in 1169 patients receiving aprepitant and highly emetogenic chemotherapy, the adverse experience profile was generally similar to that seen in the other HEC studies with aprepitant.
''Moderately Emetogenic Chemotherapy (MEC)''
=====Skin and Hypersensitivy Reactions=====
* In 2 well-controlled clinical trials in patients receiving moderately emetogenic cancer chemotherapy, 868 patients were treated with the aprepitant regimen during Cycle 1 of chemotherapy and 686 of these patients continued into extensions for up to 4 cycles of chemotherapy. In both studies, oral aprepitant was given in combination with ondansetron and dexamethasone (aprepitant regimen).
* In the combined analysis of Cycle 1 data for these 2 studies, adverse reactions were reported in approximately 14% of patients treated with the aprepitant regimen compared with approximately 15% of patients treated with standard therapy. Treatment was discontinued due to adverse reactions in 0.7% of patients treated with the aprepitant regimen compared with 0.2% of patients treated with standard therapy.
* The most common adverse reactions reported in patients treated with the aprepitant regimen with an incidence ≥1% and greater than standard therapy are listed in Table 6.
[[File:Fosaprepitant table6.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
=====Special Senses=====
* A listing of adverse reactions in the aprepitant regimen (incidence <1%) that occurred at a greater incidence than standard therapy are presented in the Less Common Adverse Reactions subsection below.
''Less Common Adverse Reactions''
Adverse reactions reported in either HEC or MEC studies in patients treated with the * aprepitant regimen with an incidence <1% and greater than standard therapy are listed in Table 7.
[[File:Fosaprepitant table7.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
=====Urogenital=====
* In another chemotherapy induced nausea and vomiting (CINV) study, Stevens-Johnson syndrome was reported as a serious adverse reaction in a patient receiving aprepitant with cancer chemotherapy.
* The adverse experience profiles in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were similar to that observed in Cycle 1.
''Fosaprepitant''
* In an active-controlled clinical study in patients receiving highly emetogenic chemotherapy, safety was evaluated for 1143 patients receiving the 1-day regimen of EMEND for Injection 150 mg compared to 1169 patients receiving the 3-day regimen of EMEND (aprepitant). The safety profile was generally similar to that seen in prior HEC studies with aprepitant. However, infusion-site reactions occurred at a higher incidence in patients in the fosaprepitant group (3.0%) compared to those in the aprepitant group (0.5%). The reported infusion-site reactions included infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site [[thrombophlebitis]].
=====Miscellaneous=====
* The following additional adverse reactions occurred with fosaprepitant 150 mg and were not reported with the oral aprepitant regimen in the corresponding section above.
[[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
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<!--Brand Names-->
<!--Brand Names-->
|brandNames=* EMEND ®<ref>{{Cite web | title =fosaprepitant dimeglumine injection, powder, lyophilized, for solution|url =http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=44f634f4-b794-4d55-8ab7-037fdef8ff0f }}</ref>
|brandNames=* EMEND ®<ref>{{Cite web | title =fosaprepitant dimeglumine injection, powder, lyophilized, for solution|url =http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=44f634f4-b794-4d55-8ab7-037fdef8ff0f }}</ref>
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
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Overview
Fosaprepitant is a {{{drugClass}}} that is FDA approved for the treatment of {{{indication}}}. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
EMEND® for Injection is a substance P/neurokinin-1 (NK1) receptor antagonist indicated in adults for use in combination with other antiemetic agents for the:
Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin.
Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).
Limitations of Use
EMEND for Injection has not been studied for the treatment of established nausea and vomiting.
Chronic continuous administration is not recommended
Dosage
Prevention of Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy (HEC)
EMEND for Injection 150 mg (Single Dose Regimen of EMEND):
EMEND for Injection 150 mg is administered intravenously on Day 1 only as an infusion over 20-30 minutes initiated approximately 30 minutes prior to chemotherapy. No capsules of EMEND are administered on Days 2 and 3. EMEND for Injection should be administered in conjunction with a corticosteroid and a 5-HT3 antagonist as specified in Table 1. The recommended dosage of dexamethasone with EMEND for Injection 150 mg differs from the recommended dosage of dexamethasone with EMEND for Injection 115 mg on Days 3 and 4. The package insert for the co-administered 5-HT3 antagonist must be consulted prior to initiation of treatment with EMEND for Injection.
This image is provided by the National Library of Medicine.
EMEND for Injection 115 mg (3-Day Dosing Regimen of EMEND):
EMEND for Injection 115 mg is administered on Day 1 only as an infusion over 15 minutes initiated 30 minutes prior to chemotherapy. Capsules of EMEND 80 mg should be administered on Days 2 and 3. EMEND for Injection 115 mg should be administered in conjunction with a corticosteroid and a 5-HT3 antagonist as specified in Table 2. The recommended dosage of dexamethasone with EMEND for Injection 115 mg differs from the recommended dosage of dexamethasone with EMEND for Injection 150 mg on Days 3 and 4. The package insert for the co-administered 5-HT3 antagonist must be consulted prior to initiation of treatment with EMEND for Injection.
Capsules of EMEND 125 mg may be substituted for EMEND for Injection 115 mg on Day 1.
This image is provided by the National Library of Medicine.
Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy (MEC)
EMEND for Injection 115 mg (3-Day Dosing Regimen of EMEND):
EMEND for Injection 115 mg is administered on Day 1 only as an infusion over 15 minutes initiated 30 minutes prior to chemotherapy. Capsules of EMEND 80 mg should be administered on Days 2 and 3. EMEND for Injection 115 mg should be administered in conjunction with a corticosteroid and a 5-HT3 antagonist as specified in Table 3. The recommended dosage of dexamethasone with EMEND for Injection 115 mg differs from the recommended dosage of dexamethasone with EMEND for Injection 150 mg on Days 3 and 4. The package insert for the co-administered 5-HT3 antagonist must be consulted prior to initiation of treatment with EMEND for Injection.
Capsules of EMEND 125 mg may be substituted for EMEND for Injection 115 mg on Day 1.
This image is provided by the National Library of Medicine.
Preparation of EMEND for Injection
This image is provided by the National Library of Medicine.
The reconstituted final drug solution is stable for 24 hours at ambient room temperature (at or below 25°C).
Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.
Caution: EMEND for Injection should not be mixed or reconstituted with solutions for which physical and chemical compatibility have not been established. EMEND for Injection is incompatible with any solutions containing divalent cations (e.g., Ca2+, Mg2+), including Lactated Ringer's Solution and Hartmann's Solution.
DOSAGE FORMS AND STRENGTHS
One 150-mg single dose glass vial: White to off-white lyophilized solid (Sterile lyophilized powder for intravenous use only after reconstitution and dilution).
One 115-mg single dose glass vial: White to off-white lyophilized solid (Sterile lyophilized powder for intravenous use only after reconstitution and dilution).
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Fosaprepitant in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Fosaprepitant in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Fosaprepitant in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Fosaprepitant in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Fosaprepitant in pediatric patients.
Aprepitant, when administered orally, is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor following the 3-day antiemetic dosing regimen for CINV. Since fosaprepitant is rapidly converted to aprepitant, do not use fosaprepitant concurrently with pimozide 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
Fosaprepitant is rapidly converted to aprepitant, which is a moderate inhibitor of CYP3A4 when administered as a 3-day antiemetic dosing regimen for CINV. Fosaprepitant should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by aprepitant or fosaprepitant could result in elevated plasma concentrations of these concomitant medications. When fosaprepitant is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When aprepitant is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant.
Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine and vincristine. In clinical studies, the oral aprepitant 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 the oral aprepitant regimen was coadministered.
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 [see DRUG INTERACTIONS (7.1)].
Hypersensitivity Reactions
Isolated reports of immediate hypersensitivity reactions including flushing, erythema, dyspnea, and anaphylaxis have occurred during infusion of fosaprepitant. These hypersensitivity reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. Reinitiation of the infusion is not recommended in patients who experience these symptoms during first-time use.
Coadministration with Warfarin (a CYP2C9 substrate)
Coadministration of fosaprepitant or aprepitant 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 fosaprepitant with each chemotherapy cycle.
Coadministration with Hormonal Contraceptives
Upon coadministration with fosaprepitant or aprepitant, the efficacy of hormonal contraceptives may be reduced during and for 28 days following the last dose of either fosaprepitant or aprepitant. Alternative or back-up methods of contraception should be used during treatment with and for 1 month following the last dose of fosaprepitant or aprepitant.
Chronic Continuous Use
Chronic continuous use of EMEND for Injection 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
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Since EMEND for Injection is converted to aprepitant, those adverse reactions associated with aprepitant might also be expected to occur with EMEND for Injection.
The overall safety of fosaprepitant was evaluated in approximately 1100 individuals and the overall safety of aprepitant was evaluated in approximately 6500 individuals.
Oral Aprepitant
Highly Emetogenic Chemotherapy (HEC)
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. Oral aprepitant was given in combination with ondansetron and dexamethasone.
In Cycle 1, adverse reactions were reported in approximately 17% of patients treated with the aprepitant regimen compared with approximately 13% of patients treated with standard therapy. Treatment was discontinued due to adverse reactions in 0.6% of patients treated with the aprepitant regimen compared with 0.4% of patients treated with standard therapy.
The most common adverse reactions reported in patients treated with the aprepitant regimen with an incidence ≥1% and greater than standard therapy are listed in Table 5.
This image is provided by the National Library of Medicine.
A listing of adverse reactions in the aprepitant regimen (incidence <1%) that occurred at a greater incidence than standard therapy are presented in the Less Common Adverse Reactions subsection below.
In an additional active-controlled clinical study in 1169 patients receiving aprepitant and highly emetogenic chemotherapy, the adverse experience profile was generally similar to that seen in the other HEC studies with aprepitant.
Moderately Emetogenic Chemotherapy (MEC)
In 2 well-controlled clinical trials in patients receiving moderately emetogenic cancer chemotherapy, 868 patients were treated with the aprepitant regimen during Cycle 1 of chemotherapy and 686 of these patients continued into extensions for up to 4 cycles of chemotherapy. In both studies, oral aprepitant was given in combination with ondansetron and dexamethasone (aprepitant regimen).
In the combined analysis of Cycle 1 data for these 2 studies, adverse reactions were reported in approximately 14% of patients treated with the aprepitant regimen compared with approximately 15% of patients treated with standard therapy. Treatment was discontinued due to adverse reactions in 0.7% of patients treated with the aprepitant regimen compared with 0.2% of patients treated with standard therapy.
The most common adverse reactions reported in patients treated with the aprepitant regimen with an incidence ≥1% and greater than standard therapy are listed in Table 6.
This image is provided by the National Library of Medicine.
A listing of adverse reactions in the aprepitant regimen (incidence <1%) that occurred at a greater incidence than standard therapy are presented in the Less Common Adverse Reactions subsection below.
Less Common Adverse Reactions
Adverse reactions reported in either HEC or MEC studies in patients treated with the * aprepitant regimen with an incidence <1% and greater than standard therapy are listed in Table 7.
This image is provided by the National Library of Medicine.
In another chemotherapy induced nausea and vomiting (CINV) study, Stevens-Johnson syndrome was reported as a serious adverse reaction in a patient receiving aprepitant with cancer chemotherapy.
The adverse experience profiles in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were similar to that observed in Cycle 1.
Fosaprepitant
In an active-controlled clinical study in patients receiving highly emetogenic chemotherapy, safety was evaluated for 1143 patients receiving the 1-day regimen of EMEND for Injection 150 mg compared to 1169 patients receiving the 3-day regimen of EMEND (aprepitant). The safety profile was generally similar to that seen in prior HEC studies with aprepitant. However, infusion-site reactions occurred at a higher incidence in patients in the fosaprepitant group (3.0%) compared to those in the aprepitant group (0.5%). The reported infusion-site reactions included infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site thrombophlebitis.
The following additional adverse reactions occurred with fosaprepitant 150 mg and were not reported with the oral aprepitant regimen in the corresponding section above.
File:XXXXX.pngThis image is provided by the National Library of Medicine.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Fosaprepitant in the drug label.
