aprepitant

REMS

IV: PO: Prevention of:
- Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (in combination with other antiemetic agents) (Cinvanti and Emend);
- Nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (in combination with other antiemetic agents) (Cinvanti and Emend).
IV: Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (in combination with other antiemetic agents) (Cinvanti).
IV: Prevention of postoperative nausea and vomiting (Aponvie).

Action ⬆ ⬇

Acts as a selective antagonist at substance P/neurokinin 1 (NK₁) receptors in the brain.

Therapeutic effects:

Decreased nausea and vomiting associated with chemotherapy or surgical procedures.
Augments the antiemetic effects of dexamethasone and 5-HT₃ antagonists in patients receiving chemotherapy.

Pharmacokinetics ⬆ ⬇

Absorption: 60–65% absorbed following oral administration. IV administration results in complete bioavailability.

Distribution: Crosses the blood brain barrier; remainder of distribution unknown.

Protein Binding: 95–99%.

Metabolism/Excretion: Mostly metabolized by the liver (CYP3A4 enzyme system); not renally excreted.

Half-Life: 9–13 hr.

Time/Action Profile ⬆ ⬇

(antiemetic effect)

ROUTE	ONSET	PEAK	DURATION
PO	1 hr	4 hr*	24 hr
IV	rapid	end of infusion*	24 hr

*Plasma concentration.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use with pimozide;
OB: Pregnancy (IV only; contains alcohol).

Use Cautiously in:

OB: Safety not established in pregnancy (PO only);
Rep: Women of reproductive potential;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children 18 yr (IV) or 6 mo (PO).

Adv. Reactions/Side Effects ⬆ ⬇

CV: dizziness, fatigue, weakness

Derm: STEVENS-JOHNSON SYNDROME

GI: diarrhea

Neuro: headache

Misc: hiccups, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

May significantly ↑ levels of pimozide, which can ↑ risk of torsades de pointes; concurrent use contraindicated.
May ↑ levels of CYP3A4 substrates, including docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine, midazolam, triazolam, and alprazolam; concurrent use should be undertaken with caution.
Moderate or strong CYP3A4 inhibitors, including ketoconazole, itraconazole, nefazodone, clarithromycin, ritonavir, nelfinavir, and diltiazem) may ↑ levels and risk of adverse reactions.
Strong CYP3A4 inducers, including rifampin, carbamazepine, and phenytoin may ↓ levels and effects.
↑levels and effects of dexamethasone (regimen reflects a 50% dose ↓); a similar effect occurs with methylprednisolone (↓ IV dose by 25%, ↓ PO dose by 50% when used concurrently).
May ↓ the effects of warfarin (carefully monitor INR for 2 wk), oral contraceptives (use alternate method), and phenytoin.

Route/Dosage ⬆ ⬇

Prevention of Acute and Delayed Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy

PO (Adults and Children ≥12 yr): Capsules: 125 mg given 1 hr prior to chemotherapy (Day 1), then 80 mg once daily for 2 days (Days 2 and 3). Suspension (if unable to swallow capsules): 3 mg/kg (max dose = 125 mg) given 1 hr prior to chemotherapy (Day 1), then 2 mg/kg (max dose = 80 mg) once daily for 2 days (Days 2 and 3).
IV (Adults ): Cinvanti: 130 mg given 30 min prior to chemotherapy on Day 1 only.
PO (Children 6 mo–<12 yr and >6 kg): Suspension: 3 mg/kg (max dose = 125 mg) given 1 hr prior to chemotherapy (Day 1), then 2 mg/kg (max dose = 80 mg) once daily for 2 days (Days 2 and 3).

Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy

PO (Adults and Children ≥12 yr): Capsules: 125 mg given 1 hr prior to chemotherapy (Day 1), then 80 mg once daily for 2 days (Days 2 and 3). Suspension (if unable to swallow capsules): 3 mg/kg (max dose = 125 mg) given 1 hr prior to chemotherapy (Day 1), then 2 mg/kg (max dose = 80 mg) once daily for 2 days (Days 2 and 3).
IV (Adults ): Cinvanti (single–dose regimen for delayed nausea/vomiting): 130 mg given 30 min prior to chemotherapy on Day 1 (with dexamethasone 12 mg PO given 30 min prior to chemotherapy and a 5-HT₃ antagonist prior to chemotherapy). Cinvanti (3–day regimen): 100 mg given 30 min prior to chemotherapy on Day 1 (with dexamethasone 12 mg PO given 30 min prior to chemotherapy and a 5-HT₃ antagonist prior to chemotherapy). Continue aprepitant 80 mg PO on Days 2 and 3.
PO (Children 6 mo–<12 yr and >6 kg): Suspension: 3 mg/kg (max dose = 125 mg) given 1 hr prior to chemotherapy (Day 1), then 2 mg/kg (max dose = 80 mg) once daily for 2 days (Days 2 and 3).

Prevention of Postoperative Nausea and Vomiting

IV (Adults ): Aponvie: 32 mg as a single dose administered prior to induction of anesthesia.

Availability ⬆ ⬇

(Generic available)

Capsules (Emend): 40 mg; 80 mg; 125 mg
Powder for oral suspension (Emend): 125 mg/pouch
Emulsion for injection (Aponvie, Cinvanti) (contains alcohol): 7.2 mg/mL

Assessment ⬆ ⬇

Assess nausea, vomiting, appetite, bowel sounds, and abdominal pain prior to and following administration.
Monitor hydration, nutritional status, and intake and output. Patients with severe nausea and vomiting may require IV fluids in addition to antiemetics.
Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe rash or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, skin peeling, sores, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Monitor for signs and symptoms of infusion site reaction (erythema, edema, pain, thrombophlebitis). Treat symptomatically. Avoid infusion into small veins or through a butterfly catheter.
Monitor for signs and symptoms of hypersensitivity reactions (flushing, erythema, dyspnea, hypotension, syncope) periodically during therapy. If symptoms occur, discontinue therapy and treat symptoms; do not reinitiate therapy if symptoms occur with first use.

Lab Test Considerations:

Monitor clotting status closely during the 2 wk period, especially at 7–10 days, following aprepitant therapy in patients on chronic warfarin therapy.
- May cause mild, transient ↑ in alkaline phosphatase, AST, ALT, and BUN.
- May cause proteinuria, erythrocyturia, leukocyturia, hyperglycemia, hyponatremia, and ↑ leukocytes.
- May cause ↓ hemoglobin and WBC.

Implementation ⬆ ⬇

For chemotherapy, aprepitant is given as part of a regimen that includes a corticosteroid and a 5-HT₃ antagonist (see Route/Dosage).
PO: Administer daily for 3 days. Day 1: administer 1 hr prior to chemotherapy. Days 2 and 3: administer once in the morning. May be administered without regard to food. DNC: Swallow capsules whole; do not open, crush, or chew.
- Oral suspension may be used for pediatric patients or those with difficulty swallowing. Follow manufacture's instructions for preparing suspension. Refrigerate suspension; may be stored at room temperature for up to 3 hrs before use. To administer, take cap off, place dispenser in patient's mouth along inner cheek. Dispense slowly. Discard after 72 hrs.

IV Administration:

Cinvanti

Complete injection or infusion 30 min prior to chemotherapy.
Withdraw 18 mL for the 130 mg dose or 14 mL for the 100 mg dose from the vial. Do not dilute.
Rate: Inject over 2 min. Flush line with 0.9% NaCl before and after injection.
Intermittent Infusion: Diluent: 0.9% NaCl or D5W.For Highly-Emetogenic Chemotherapy: Using 130 mL of diluent, withdraw 18 mg aprepitant from vial and add to bag for 148 mL. For Moderately-Emetogenic Chemotherapy: Using 100 mL of diluent, withdraw 14 mL aprepitant from vial and add to bag for 114 mL. Mix by gently inverting bag 4–5 times. Solution is an opaque, off-white emulsion. Do not administer solutions that are discolored or contain particulate matter. May be stored at room temperature for 6 hrs if mixed with 0.9% NaCl or 12 hrs if mixed with D5W or in refrigerator for up to 72 hrs.
Rate: Infuse over 30 min.

Emend

Complete injection or infusion 30 min prior to chemotherapy.
Intermittent Infusion: Reconstitution: Inject 5 mL of 0.9% NaCl into vial along the vial wall to prevent foaming. Swirl vial gently. Avoid shaking and jetting 0.9% NaCl into the vial.Diluent: Withdraw entire volume from vial and transfer to infusion bag containing 145 mL of 0.9% NaCl for a volume of 150 mL.Final concentration of 1 mg/mL.Gently invert bag 2 to 3 times. Solution is stable for 24 hrs at room temperature. Discard unused portion.
Rate: Infuse over 20–30 min for adults, over 30 min for children 12–17 yrs, or over 60 min for children 6 mos to <12 yrs. For children may also be given as a 3–day regimen via central venous catheter. For children 12–17 yrs, Day 1: infuse 115 mg over 30 min; Day 2 and 3: infuse 80 mg over 30 min. For children 6 mos to <12 yrs, Day 1: infuse 3 mg/kg up to 115 mg over 60 min; Day 2 and 3: infuse 2 mg/kg up to 80 mg over 60 min.

Aponvie

Withdraw 4.4 mL from vial. Solution is opaque and off-white to amber. Do not administer solutions that are discolored or contain particulate matter. Flush the infusion line with 0.9% NaCl before and after administration.
Rate: Administer over 30 sec prior to induction of anesthesia.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take aprepitant as directed. Direct patient to read the Patient Package Insert before starting therapy and each time Rx renewed in case of changes.
Instruct patient to notify health care professional if nausea and vomiting occur prior to administration.
Advise patient to notify health care professional immediately if symptoms of hypersensitivity reaction (hives, rash, itching, redness of the face/skin, difficulty in breathing or swallowing) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient and family to use general measures to decrease nausea (begin with sips of liquids and small, non-greasy meals; provide oral hygiene; remove noxious stimuli from environment).
Rep: Caution females of reproductive potential that aprepitant may decrease efficacy of oral contraceptives. Advise patient to use effective alternate nonhormonal methods of contraception during and for 1 mo following treatment. Advise females of reproductive potential that Cinvanti contains alcohol and may cause fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Avoid use of Cinvanti during pregnancy. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇