aprepitant

Therapeutic Classification: antiemetics

Pharmacologic Classification: neurokinin antagonists

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).

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.

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 via the CYP3A4 isoenzyme.

Half-Life: 9–13 hr.

( antiemetic effect)

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

* Plasma concentration.

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 <12 yr (PO).

CV: dizziness, fatigue, weakness

Derm: STEVENS-JOHNSON SYNDROME (SJS)

GI: diarrhea

Neuro: headache

Misc: hiccups, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Drug-drug:

May significantly ↑ levels of pimozide, which can ↑ risk of torsades de pointes; concurrent use contraindicated.
May ↑ levels and risk of toxicity 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 toxicity.
Strong CYP3A4 inducers, including rifampin, carbamazepine, and phenytoin, may ↓ levels and effectiveness.
May ↑ levels and risk of toxicity 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.

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

PO (Adults and Children ≥12 yr): 125 mg given 1 hr prior to chemotherapy (Day 1); then 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.

Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Chemotherapy

PO (Adults and Children ≥12 yr): 125 mg given 1 hr prior to chemotherapy (Day 1); then 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.

Prevention of Postoperative Nausea and Vomiting

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

(Generic available)

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

Assess nausea, vomiting, appetite, bowel sounds, and abdominal pain before 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 SJS. Discontinue therapy if severe rash or if accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, skin peeling, sores, oral lesions, conjunctivitis, hepatitis, 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 (anaphylaxis, flushing, erythema, dyspnea, hypotension, syncope) periodically during therapy. If symptoms occur, discontinue therapy and implement supportive measures (epinephrine) and treat symptoms; do not reinitiate therapy if symptoms occur with 1st use.

Lab Test Considerations:

Monitor INR 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 ↓ hemoglobin and WBC.

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 before 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.

IV Administration:

Cinvanti

Complete injection or infusion 30 min before chemotherapy.
IV Push: Withdraw 18 mL for the 130-mg dose or 14 mL for the 100-mg dose from the vial. Do not dilute.
Intermittent Infusion: For 130-mg dose, withdraw 18 mL from the injection vial and transfer into diluent. For 100-mg dose, withdraw 14 mL from the aprepitant injection vial and transfer into diluent. Diluent: 100 mL of 0.9% NaCl or D5W. 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 hr if mixed with 0.9% NaCl or 12 hr if mixed with D5W or in refrigerator for up to 72 hr. Concentration: 0.88–1.1 mg/mL.
Y-Site Incompatibility:
- Solutions containing divalent cations (calcium, magnesium)

Aponvie

IV Push: 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. Do not dilute.Rate:
Y-Site Incompatibility:
- Solutions containing divalent cations (calcium, magnesium)

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed.
Advise 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 to notify health care professional if nausea and vomiting occur before administration.
Advise patient to notify health care professional immediately if signs/symptoms of hypersensitivity reactions occur.
Advise patient/caregiver to use general measures to ↓ nausea (begin with sips of liquids and small, nongreasy meals; provide oral hygiene; remove noxious stimuli from environment).
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise women of reproductive potential that aprepitant may ↓ efficacy of oral contraceptives. Advise patient to use effective alternate nonhormonal methods of contraception during and for 1 mo following treatment. Advise women of reproductive potential that Cinvanti contains alcohol and may cause fetal harm including CNS abnormalities, behavioral disorders, and impaired intellectual development. Avoid use of Cinvanti during pregnancy.

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

Aponvie, Cinvanti, Emend

NDC Code

0006- Merck Sharp & Dohme LLC
- 0006-0461- EMEND
  - 0006-0461-02- 2 CAPSULE in 1 DOSE PACK (0006-0461-02)

0006- Merck Sharp & Dohme LLC
- 0006-0461- EMEND
  - 0006-0461-12- 2 CAPSULE in 1 DOSE PACK (0006-0461-12)

0006- Merck Sharp & Dohme LLC
- 0006-3066- EMEND
  - 0006-3066-03- 1 POUCH in 1 CARTON (0006-3066-03) / 1 POWDER, FOR SUSPENSION in 1 POUCH (0006-3066-01)

0006- Merck Sharp & Dohme LLC
- 0006-3862- EMEND
  - 0006-3862-03- 1 KIT in 1 DOSE PACK (0006-3862-03) * 1 CAPSULE in 1 CAPSULE * 1 CAPSULE in 1 CAPSULE

0006- Merck Sharp & Dohme LLC
- 0006-3862- EMEND
  - 0006-3862-13- 1 KIT in 1 DOSE PACK (0006-3862-13) * 1 CAPSULE in 1 CAPSULE * 1 CAPSULE in 1 CAPSULE

0781- Sandoz Inc
- 0781-2321- Aprepitant
  - 0781-2321-06- 1 BLISTER PACK in 1 CARTON (0781-2321-06) / 1 CAPSULE in 1 BLISTER PACK

0781- Sandoz Inc
- 0781-2321- Aprepitant
  - 0781-2321-51- 5 BLISTER PACK in 1 CARTON (0781-2321-51) / 1 CAPSULE in 1 BLISTER PACK

0781- Sandoz Inc
- 0781-2322- Aprepitant
  - 0781-2322-46- 2 CAPSULE in 1 DOSE PACK (0781-2322-46)

0781- Sandoz Inc
- 0781-2322- Aprepitant
  - 0781-2322-68- 1 BLISTER PACK in 1 CARTON (0781-2322-68) / 6 CAPSULE in 1 BLISTER PACK (0781-2322-06)

0781- Sandoz Inc
- 0781-2323- Aprepitant
  - 0781-2323-68- 1 BLISTER PACK in 1 CARTON (0781-2323-68) / 6 CAPSULE in 1 BLISTER PACK (0781-2323-06)

0781- Sandoz Inc
- 0781-4063- Aprepitant
  - 0781-4063-36- 1 KIT in 1 DOSE PACK (0781-4063-36) * 1 CAPSULE in 1 BLISTER PACK * 2 CAPSULE in 1 BLISTER PACK

13612- Wisdom Pharmaceutical Co.,Ltd.
- 13612-0024-
  - 13612-0024-0- 10 kg in 1 BAG (13612-0024-0)

13668- Torrent Pharmaceuticals Limited
- 13668-591- APREPITANT
  - 13668-591-81- 1 BLISTER PACK in 1 CARTON (13668-591-81) / 1 CAPSULE in 1 BLISTER PACK (13668-591-80)

13668- Torrent Pharmaceuticals Limited
- 13668-591- APREPITANT
  - 13668-591-82- 5 BLISTER PACK in 1 CARTON (13668-591-82) / 1 CAPSULE in 1 BLISTER PACK (13668-591-80)

13668- Torrent Pharmaceuticals Limited
- 13668-592- APREPITANT
  - 13668-592-84- 2 BLISTER PACK in 1 CARTON (13668-592-84) / 1 CAPSULE in 1 BLISTER PACK (13668-592-85)

13668- Torrent Pharmaceuticals Limited
- 13668-592- APREPITANT
  - 13668-592-86- 3 BLISTER PACK in 1 CARTON (13668-592-86) / 2 CAPSULE in 1 BLISTER PACK (13668-592-83)

13668- Torrent Pharmaceuticals Limited
- 13668-593- APREPITANT
  - 13668-593-86- 6 BLISTER PACK in 1 CARTON (13668-593-86) / 1 CAPSULE in 1 BLISTER PACK (13668-593-80)

13668- Torrent Pharmaceuticals Limited
- 13668-594- APREPITANT
  - 13668-594-87- 1 KIT in 1 DOSE PACK (13668-594-87) * 2 CAPSULE in 1 BLISTER PACK * 1 CAPSULE in 1 BLISTER PACK

47426- Heron Therapeutics, Inc.
- 47426-201- CINVANTI
  - 47426-201-01- 1 VIAL, GLASS in 1 CARTON (47426-201-01) / 18 mL in 1 VIAL, GLASS

47426- Heron Therapeutics, Inc.
- 47426-401- APONVIE
  - 47426-401-10- 10 VIAL, GLASS in 1 CARTON (47426-401-10) / 4.4 mL in 1 VIAL, GLASS (47426-401-01)

50370- MSN Pharmachem Private Limited
- 50370-0022-
  - 50370-0022-1- 60 kg in 1 DRUM (50370-0022-1)

50370- MSN Pharmachem Private Limited
- 50370-0038-
  - 50370-0038-1- 60 kg in 1 DRUM (50370-0038-1)

50370- MSN Pharmachem Private Limited
- 50370-0048-
  50370-0048-1- 60 kg in 1 DRUM (50370-0048-1)

51407- Golden State Medical Supply, Inc.
- 51407-701- APREPITANT
  51407-701-01- 1 BLISTER PACK in 1 CARTON (51407-701-01) / 1 CAPSULE in 1 BLISTER PACK (51407-701-11)

51407- Golden State Medical Supply, Inc.
- 51407-701- APREPITANT
  - 51407-701-05- 5 BLISTER PACK in 1 CARTON (51407-701-05) / 1 CAPSULE in 1 BLISTER PACK (51407-701-11)

51407- Golden State Medical Supply, Inc.
- 51407-702- APREPITANT
  - 51407-702-02- 2 BLISTER PACK in 1 CARTON (51407-702-02) / 1 CAPSULE in 1 BLISTER PACK (51407-702-11)

51407- Golden State Medical Supply, Inc.
- 51407-702- APREPITANT
  - 51407-702-06- 3 BLISTER PACK in 1 CARTON (51407-702-06) / 2 CAPSULE in 1 BLISTER PACK (51407-702-22)

51407- Golden State Medical Supply, Inc.
- 51407-703- APREPITANT
  - 51407-703-06- 6 BLISTER PACK in 1 CARTON (51407-703-06) / 1 CAPSULE in 1 BLISTER PACK (51407-703-66)

51407- Golden State Medical Supply, Inc.
- 51407-704- APREPITANT
  - 51407-704-03- 1 KIT in 1 DOSE PACK (51407-704-03) * 2 CAPSULE in 1 BLISTER PACK * 1 CAPSULE in 1 BLISTER PACK

55111- Dr. Reddy's Laboratories Limited
- 55111-892-
  - 55111-892-00- 1 kg in 1 DRUM (55111-892-00)

56125- Novo Nordisk Production Ireland Limited
- 56125-632-
  56125-632-02- 1 BAG in 1 DRUM (56125-632-02) / 40000 CAPSULE in 1 BAG

56125- Novo Nordisk Production Ireland Limited
- 56125-633-
  56125-633-03- 1 BAG in 1 DRUM (56125-633-03) / 28000 CAPSULE in 1 BAG

56125- Novo Nordisk Production Ireland Limited
- 56125-634-
  56125-634-01- 22 kg in 1 DRUM (56125-634-01)

59285- Optimus Drugs Private Limited
- 59285-015-
  59285-015-01- 50 kg in 1 DRUM (59285-015-01)

64567- Inke SA
- 64567-0021-
  64567-0021-0- 25 kg in 1 DRUM (64567-0021-0)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-1- 2 kg in 1 DRUM (65085-0043-1)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-2- 5 kg in 1 DRUM (65085-0043-2)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-3- 10 kg in 1 DRUM (65085-0043-3)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-4- 20 kg in 1 DRUM (65085-0043-4)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-5- 2 kg in 1 DRUM (65085-0043-5)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-6- 5 kg in 1 DRUM (65085-0043-6)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-7- 2 kg in 1 DRUM (65085-0043-7)

65085- Piramal Pharma Limited
- 65085-0043-
  65085-0043-8- 5 kg in 1 DRUM (65085-0043-8)

65372- Jubilant Pharmova Limited
- 65372-1169-
  65372-1169-2- 20 kg in 1 DRUM (65372-1169-2)

65977- Hetero Drugs Limited
- 65977-0024-
  65977-0024-1- 5 kg in 1 DRUM (65977-0024-1)

66039- Glenmark Life Sciences Limited
- 66039-851-
  66039-851-03- 50 kg in 1 DRUM (66039-851-03)

66039- Glenmark Life Sciences Limited
- 66039-880-
  66039-880-03- 50 kg in 1 DRUM (66039-880-03)

68462- Glenmark Pharmaceuticals Inc., USA
- 68462-112- Aprepitant
  68462-112-33- 1 KIT in 1 DOSE PACK (68462-112-33) * 2 CAPSULE in 1 BLISTER PACK * 1 CAPSULE in 1 BLISTER PACK

68462- Glenmark Pharmaceuticals Inc., USA
- 68462-583- Aprepitant
  - 68462-583-11- 1 BLISTER PACK in 1 CARTON (68462-583-11) / 10 CAPSULE in 1 BLISTER PACK

68462- Glenmark Pharmaceuticals Inc., USA
- 68462-583- Aprepitant
  - 68462-583-40- 1 BLISTER PACK in 1 CARTON (68462-583-40) / 1 CAPSULE in 1 BLISTER PACK

68462- Glenmark Pharmaceuticals Inc., USA
- 68462-583- Aprepitant
  - 68462-583-85- 5 BLISTER PACK in 1 CARTON (68462-583-85) / 1 CAPSULE in 1 BLISTER PACK

68462- Glenmark Pharmaceuticals Inc., USA
- 68462-584- Aprepitant
  - 68462-584-58- 2 CAPSULE in 1 DOSE PACK (68462-584-58)

68462- Glenmark Pharmaceuticals Inc., USA
- 68462-584- Aprepitant
  - 68462-584-76- 1 BLISTER PACK in 1 CARTON (68462-584-76) / 6 CAPSULE in 1 BLISTER PACK (68462-584-40)

68462- Glenmark Pharmaceuticals Inc., USA
- 68462-585- Aprepitant
  - 68462-585-76- 1 BLISTER PACK in 1 CARTON (68462-585-76) / 6 CAPSULE in 1 BLISTER PACK (68462-585-40)

72643- SOLARA ACTIVE PHARMA SCIENCES LIMITED
- 72643-020-
  - 72643-020-02- 5 kg in 1 DRUM (72643-020-02)

72643- SOLARA ACTIVE PHARMA SCIENCES LIMITED
- 72643-020-
  72643-020-04- 25 kg in 1 DRUM (72643-020-04)

72643- SOLARA ACTIVE PHARMA SCIENCES LIMITED
- 72643-020-
  72643-020-05- 50 kg in 1 DRUM (72643-020-05)

73005- OLON ACTIVE PHARMACEUTICAL INGREDIENTS INDIA PRIVATE LIMITED
- 73005-0009-
  73005-0009-1- 1 BAG in 1 DRUM (73005-0009-1) / 1 BAG in 1 BAG / 25 kg in 1 BAG

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Code ⬆