aprepitant (Rx)

Brand and Other Names:Cinvanti, Emend, more...fosaprepitant
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule (aprepitant)

  • Emend
  • 40mg
  • 80mg
  • 125mg

injection, powder for reconstitution (fosaprepitant)

  • Emend
  • 150mg

oral suspension

  • Emend
  • 125mg/pouch (once pouch is mixed with 4.6 mL drinking water, resulting suspension yields 25mg/mL)

injection, emulsion (aprepitant)

  • Cinvanti
  • 7.2mg/mL (130mg/18mL)
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Chemotherapy-Induced Nausea & Vomiting

Indicated for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin; also indicated for nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)

Use in combination with other antiemetics

IV

  • HEC
    • Day 1: 150 mg IV infused over 20-30 minutes ~30 minutes before chemotherapy plus dexamethasone 12 mg PO and a 5-HT3 antagonist
    • Day 2: Dexamethasone 8 mg PO in AM
    • Days 3 and 4: Dexamethasone 8 mg PO BID (morning and evening)
    • Note: A 50% dosage reduction of dexamethasone on Days 1 and 2 is recommended to account for a drug interaction with aprepitant
  • MEC
    • Day 1: 150 mg IV infused over 20-30 minutes ~30 minutes before chemotherapy plus dexamethasone 12 mg PO and a 5-HT3 antagonist

IV emulsion

  • HEC
    • Day 1: 130 mg IV infused over 30 minutes ~30 minutes before chemotherapy plus dexamethasone 12 mg PO and a 5-HT3 antagonist
    • Day 2: Dexamethasone 8 mg PO in AM
    • Days 3 and 4: Dexamethasone 8 mg PO BID (morning and evening)
    • Note: A 50% dosage reduction of dexamethasone on Days 1 and 2 is recommended to account for a drug interaction with aprepitant
  • MEC
    • Day 1: 100 mg IV infused over 30 minutes ~30 minutes before chemotherapy plus dexamethasone 12 mg PO and a 5-HT3 antagonist
    • Days 2-3: 80 mg PO 1 hr prior to chemotherapy
    • Note: A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with aprepitant

Oral

  • Day 1: 125 mg PO 1 hr prior to chemotherapy plus dexamethasone 12 mg PO (30 minutes before chemotherapy) and a 5-HT3 antagonist
  • Days 2-3: 80 mg PO 1 hr prior to chemotherapy plus dexamethasone 8 mg PO qAM
  • Day 4: Dexamethasone 8 mg PO in AM

Postoperative Nausea & Vomiting

Indicated for prevention of PONV

40 mg PO within 3 hr prior to anesthesia induction

Dosage Modifications

Renal impairment

  • Severe (CrCl <30 mL/min): Decreased AUC of total aprepitant (unbound and protein bound) by 21% and Cmax decreased by 32%, compared to healthy subjects (CrCl >80 mL/min)
  • ESRD undergoing hemodialysis: Decreased AUC of total aprepitant by 42% and Cmax decreased by 32%

Hepatic impairment

  • Mild-to-moderate (Child Pugh score 5 to 9): No dosage adjustment necessary
  • Severe (Child Pugh score >9): Safety and efficacy has not been established

Dosing Considerations

Limitation of use

  • Cinvanti has not been studied for the treatment of established nausea and vomiting

Dosage Forms & Strengths

capsule (aprepitant)

  • 80mg
  • 125mg

oral suspension

  • 125mg/pouch (once pouch is mixed with 4.6 mL drinking water, resulting suspension yields 25mg/mL)

Chemotherapy-Induced Nausea & Vomiting

Indicated 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, and for moderately emetogenic cancer chemotherapy (MEC)

Capsule: Aged <12 years and weight <30 kg: Safety and efficacy not established

Oral suspension: Aged <6 months: Safety and efficacy not established

IV emulsion: Aged <18 years: Safety and efficacy not established

Capsule for aged ≥12 years or <12 years and weight ≥30 kg

  • Day 1: 125 mg PO 1 hr prior to chemotherapy plus dexamethasone 12 mg PO (30 minutes before chemotherapy) and a 5-HT3 antagonist
  • Days 2 and 3: 80 mg PO 1 hr prior to chemotherapy plus dexamethasone 8 mg PO qAM
  • Day 4: Dexamethasone 8 mg PO in AM

Oral suspension for aged ≥6 months to <12 years

  • Day 1: 3 mg/kg PO 1 hr prior to chemotherapy Days 2 and 3: 2 mg/kg PO 1 hr prior to chemotherapy
  • Administer with concomitant dexamethasone and 5-HT3 antagonist (eg, ondansetron)

Dosing Considerations

Children must be able to swallow capsule whole

Has not been studied for treatment of established nausea and vomiting

Chronic continuous administration 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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Interactions

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            Adverse Effects

            CINV: generally similar to standard treatments

            PONV: generally similar to ondansetron

            >10% (only seen in CINV)

            Headache

            Asthenia/fatigue

            Anorexia

            Constipation

            Diarrhea

            Nausea

            Alopecia

            Hiccups

            1-10% (selected)

            Dizziness

            Insomnia

            Bradycardia

            Hypotension

            Pharyngolargeal pain

            Mucosal inflammation

            Stomatitis

            Dyspepsia

            Anemia

            Neutropenia

            Hot flash

            Pruritus

            Dehydration

            Fever

            < 1%

            Candidiasis

            Staphylococcal infection

            Anemia

            Febrile neutropenia

            Weight gain

            Polydipsia

            Disorientation

            Euphoria

            Anxiety

            Dizziness

            Dream abnormality

            Cognitive disorder

            Lethargy

            Somnolence

            Conjunctivitis

            Tinnitus

            Bradycardia

            Palpitations

            Hot flush

            Flushing

            Pharyngitis

            Sneezing

            Cough

            Postnasal drip

            Throat irritation

            Nausea

            Acid reflux

            Dysgeusia

            Epigastric discomfort

            Edema

            Chest discomfort

            Malaise

            Thirst

            Chills

            Gait disturbance

            Postmarketing Reports

            Rash, urticaria, rarely Stevens-Johnson syndrome/toxic epidermal necrolysis; ifosfamide-induced neurotoxicity reported after aprepitant and ifosfamide coadministration, hypersensitivity reactions including anaphylaxis and anaphylactic shock

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            Warnings

            Contraindications

            Hypersensitivity

            Concomitant pimozide or cisapride (see Cautions)

            Cautions

            Monitor patients during and after infusion; if hypersensitivity reactions occur, discontinue infusion and administer appropriate medical therapy; do not reinitiate therapy in patients who experience these symptoms with first-time use

            IV: Isolated reports of immediate hypersensitivity reactions including flushing, erythema, and dyspnea during infusion of fosaprepitant; discontinuation infusion and do reinitiate

            Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate

            Drug interactions overview

            • Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4
            • Concomitant use of aprepitant and CYP3A4 substrates may result in increased plasma concentration of the CYP3A4 drugs
            • Concomitant use of pimozide with aprepitant is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, which may prolong QT interval (see Contraindications)
            • Avoid concomitant use of aprepitant with strong or moderate CYP3A4 inhibitors (eg, ketoconazole, diltiazem) may increase plasma concentrations and effects of aprepitant
            • Avoid concomitant use of aprepitant with strong CYP3A4 inducers (eg, rifampin) may result in a substantial reduction in aprepitant plasma concentrations and decreased efficacy
            • Decreased corticosteroid dose by 25% (IV) or 50% (PO) on days aprepitant is administered
            • Coadministration with benzodiazepines metabolized by CYP3A4 may increase levels and/or effects of midazolam or other benzodiazepines (alprazolam, triazolam)
            • Coadministration with warfarin may decrease warfarin exposure and prolong prothrombin time (INR); patients on chronic warfarin therapy, monitor INR for 7-10 days following administration of aprepitant IV emulsion with each chemotherapy cycle
            • Coadministration with oral contraceptives may decrease estrogen and progestin exposure during administration of and for 28 days after administration of the last dose of aprepitant (see Pregnancy)
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            Pregnancy & Lactation

            Pregnancy

            Insufficient data on use in pregnant women to inform a drug associated risk; in animal reproduction studies, no adverse developmental effects observed in rats or rabbits exposed during period of organogenesis to systemic drug levels (AUC) ~1.5 times adult human exposure at 125-mg/80-mg/80-mg regimen

            Avoid use of aprepitant IV emulsion in pregnant women due to the alcohol content

            Coadministration with aprepitant may reduce the efficacy of hormonal contraceptives; advise females of reproductive potential using hormonal contraceptives to use an effective alternative or back-up non-hormonal contraceptive (such as condoms or spermicides) during treatment and for 1 month following the last dose of aprepitant IV emulsion or oral aprepitant, whichever is administered last

            Lactation

            It is not known whether this drug is excreted in milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors; aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors

            In animal models, aprepitant has shown to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions; animal and human studies also shown aprepitant augmenting antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis

            Absorption

            Bioavailability: 60-65% (PO)

            Peak plasma time

            • 125 mg PO once: 4 hr
            • 80 mg PO twice: 4 hr
            • 40 mg PO once: 3 hr

            Peak plasma concentration

            • Emend
              • 125 mg PO once: 1.6 mcg/mL
              • 80 mg PO twice: 1.4 mcg/mL
              • 40 mg PO once: 0.7 mcg/mL
              • 150 mg IV once: 4.15 mcg/mL
            • Cinvanti
              • 130 mg IV once: 6.1 mcg/mL
              • 100 mg IV once: 4.3 mcg/mL

            AUC

            • Emend
              • 125 mg PO once: 19.6 mcg·hr/mL
              • 80 mg PO twice: 21.2 mcg·hr/mL
              • 150 mg IV once: 37.38 mcg·hr/mL
            • Cinvanti
              • 130 mg IV once: 43.9 mcg·hr/mL
              • 100 mg IV once: 27.8 mcg·hr/mL

            Distribution

            Protein bound: >95%

            Vd: 70 L

            Aprepitant crosses the blood brain barrier in humans

            Metabolism

            Hepatic CYP3A4 (major); CYP1A2, CYP2C19 (minor)

            Fosaprepitant (IV form) rapidly converted to aprepitant in vivo

            Enzymes inhibited: CYP3A4

            Enzymes induced: CYP2C9

            Elimination

            Half-life: 9-13 hr

            Total body clearance: 62-90 mL/min

            Excretion (IV admin): 57% urine; 45% feces

            Dialyzable: No

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            Administration

            IV Compatibility

            Fosaprepitant IV: 0.9% NaCl

            Aprepitant IV emulsion: 0.9% NaCl or D5W

            IV Incompatibilities

            Divalent cation-containing solutions (Ca++, Mg++, Zn++ etc), Hartmann's Solution, LR

            IV Preparation (Fosaprepitant)

            Aseptically inject 5 mL 0.9% NaCl into vial along the vial wall in order to prevent foaming; avoid jetting the 0.9% NaCl into the vial

            Gently swirl to dissolve; do not shake

            Aseptically withdraw entire volume from vial and transfer it into a prepared infusion bag of 145 mL 0.9% NaCl to yield a total volume of 150 mL and a final concentration of 1 mg/mL

            Gently invert bag 2-3 times to mix

            Stable for 24 hr at ambient room temperature (ie, ≤25°C [77°F])

            IV Preparation (Aprepitant IV Emulsion)

            MEC

            • Aseptically prepare infusion bag filled with 130 mL of 0.9% NaCl or D5W
            • Aseptically withdraw 18 mL from vial and transfer contents into the infusion bag to yield a total volume of 148 mL
            • Gently invert bag 4-5 times to mix; avoid shaking
            • Visually inspect bag for particulate matter and discoloration prior to administration
            • Discard bag if particulate and/or discoloration are observed
            • Stable for 6 hr (0.9% NaCl) or 12 hr (D5W) at ambient room temperature (≤25°C or 77°F)

            HEC

            • Aseptically prepare infusion bag filled with 100 mL of 0.9% NaCl or D5W
            • Aseptically withdraw 14 mL from vial and transfer contents into the infusion bag to yield a total volume of 114 mL
            • Gently invert bag 4-5 times to mix; avoid shaking
            • Visually inspect bag for particulate matter and discoloration prior to administration
            • Discard bag if particulate and/or discoloration are observed
            • Stable for 6 hr (0.9% NaCl) or 12 hr (D5W) at ambient room temperature (≤25°C or 77°F)

            IV Administration

            Fosaprepitant: Infuse IV over 20-30 min

            Aprepitant IV emulsion: Infuse IV over 30 min

            Do not mix with other drugs

            Oral Administration

            Take with or without food

            Capsule: Swallow capsule whole

            Oral suspension

            • Dose is prepared by a pharmacist and dispensed to the patient or caregiver in an oral dispenser/oral syringe; once pouch is mixed with 4.6 mL drinking water, the resulting concentration is 25 mg/mL
            • Keep the dispenser in the refrigerator until administered to the patient
            • The dose can be stored at room temperature for up to 3 hr before use
            • When ready to use, take the cap off the dispenser, place the dispenser in the patient’s mouth along the inner cheek on either the right or left side
            • Slowly administer the medicine along the inner cheek
            • Use dose within 72 hr of preparation
            • Discard any doses remaining after 72 hr

            Storage

            Capsules: Store at room temperature at 20-25°C (68-77°F)

            Oral suspension

            • Unopened pouch
              • 20-25°C (68-77°F); excursions permitted between 15-30°C (between 59-86°F)
              • Store in the original container
              • Do not open pouch until ready to prepare for use
            • Prepared dose
              • If the dose is not administered immediately after measuring, store filled oral dosing dispenser(s) in the refrigerator (between 36-46°F [2-8°C]) for up to 72 hr prior to use
              • When dispensing dose(s) to the patient or caregiver, instruct them to refrigerate the oral dosing dispenser(s) until they are ready to administer the dose
              • When ready to use, the mixture can be kept at room temperature (68-77°F [20°C-25°C]) for up to 3 hr

            Fosaprepitant IV

            • Unused vials: Store in refrigerator at 2-8°C (36-46°F)
            • Reconstituted vials and diluted solutions: Store at room temperature at (68-77°F [20°C-25°C]) for up to 24 hr

            Aprepitant IV emulsion

            • Vials
              • Store in refrigerator at 2-8°C (36-46°F)
              • Store at room temperature at (68-77°F [20°C-25°C]) up to 60 days
            • Diluted solutions
              • 0.9% NaCl solutions: Store at room temperature at (68-77°F [20°C-25°C]) for up to 6 hr
              • D5W solutions: Store at room temperature at (68-77°F [20°C-25°C]) for up to 12 hr
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
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