Indications
PO: Prevention of nausea and vomiting due to emetogenic
chemotherapy or radiation therapy. Prevention
and treatment of postoperative nausea and vomiting.
Subcut: Prevention of acute and delayed nausea and
vomiting due to moderately emetogenic chemotherapy
or anthacycline/cyclophosphamide combination
chemotherapy (with dexamethasone). Transdermal:
Prevention of nausea and vomiting due to moderately/
highly emetogenic chemotherapy.
Action
Blocks the effects of serotonin at receptor sites (selective
antagonist) located in vagal nerve terminals and in
the chemoreceptor trigger zone in the CNS. Therapeutic
Effects: Decreased incidence and severity of
nausea and vomiting following emetogenic chemotherapy,
radiation therapy, or surgery.
Pharmacokinetics
Absorption: 50% absorbed following oral administration;
transdermal enters systemic circulation via passive
diffusion through intact skin.
Distribution: Distributes into erythrocytes; remainder
of distribution is unknown.
Protein Binding: 65%.
Metabolism and Excretion: Mostly metabolized
by the liver; 12% excreted unchanged in urine.
Half-life: Patients with cancer—10–12 hr (range
0.9–31.1 hr); healthy volunteers —3–4 hr (range
0.9–15.2 hr); geriatric patients—7.7 hr (range
2.6–17.7 hr); subcutaneous—24 hr.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
PO rapid 60 min 24 hr
IV 1–3 min 30 min up to 24 hr
TD* unknown 48 hr unknown
Subcut* unknown 12 hr 7 days
*Blood levels.
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Some products
contain benzyl alcohol; avoid use in neonates; Severe
renal impairment (subcut).
Use Cautiously in: History of arrhythmias or conduction
disorders; Recent abdominal surgery (subcutaneous);
Moderate renal impairment (pfrequency of
administration); OB, Lactation: Safety not established;
Pedi: Safety and effectiveness not established in children
18 yr (oral, subcut, or transdermal) or 2 yr
(IV).
Adverse Reactions/Side Effects
CNS: headache, agitation, anxiety, CNS stimulation,
dizziness, drowsiness, headache, insomnia, weakness.
CV: hypertension, QT interval prolongation. GI: constipation,
abdominal pain, diarrhea, dyspepsia,qliver
enzymes, taste disorder. Derm: Topical—application
site reactions, photosensitivity. Misc: HYPERSENSITIVITY
REACTIONS (including anaphylaxis), SEROTONIN SYNDROME,
injection site reactions (subcutaneous) (including
infection, bruising, hematoma, bleeding, pain,
or nodules), fever.
Interactions
Drug-Drug:qrisk of extrapyramidal reactions with
other agents causing extrapyramidal reactions.q
risk of QT interval prolongation with other agents
causing QT interval prolongation. Drugs that affect
serotonergic neurotransmitter systems, including
SSRIs, SNRIs, tricyclic antidepressants, MAOIs,
fentanyl, lithium, buspirone, tramadol, methylene
blue, and triptansqrisk of serotonin syndrome.
Route/Dosage
Prevention of Nausea and Vomiting Due
to Emetogenic Chemotherapy
PO (Adults): 1 mg twice daily; 1st dose given at least
60 min prior to chemotherapy and 2nd dose 12 hr later
only on days when chemotherapy is administered; may
also be given as 2 mg once daily at least 60 min prior to
chemotherapy.
IV (Adults and Children 2–16 yr): 10 mcg/kg given
within 30 min prior to chemotherapy or 20–40 mcg/
kg/day divided once or twice daily (maximum: 3 mg/
dose or 9 mg/day).
Transdermal (Adults): One 34.3-mg patch (delivers
3.1 mg/24 hr) applied up to 48 hr prior to chemotherapy,
leave in place for at least 24 hr following chemotherapy,
may be left in place for a total of 7 days.
Prevention of Nausea and Vomiting Associated
with Radiation Therapy
PO (Adults): 2 mg taken once daily within 1 hr of radiation
therapy.
Prevention and Treatment of Postoperative
Nausea and Vomiting
IV (Adults): Prevention—1 mg prior to induction of
anesthesia or just prior to reversal of anesthesia; Treatment—
1 mg.
IV (Children 4 yr): 20–40 mcg/kg as a single dose
(maximum: 1 mg).
Prevention of Acute and Delayed Nausea
and Vomiting Due to Emetogenic Chemotherapy
Subcut (Adults): 10 mg given at least 30 min prior to
chemotherapy (with dexamethasone) on Day 1 of
chemotherapy; do not administer more frequently than
every 7 days.
Renal Impairment
Subcut (Adults): CCr 30–59 mL/min—Do not administer
more frequently than every 14 days.
Availability (generic available)
Tablets: 1 mg. Solution for intravenous injection:
0.1 mg/mL, 1 mg/mL. Solution for subcutaneous
injection (in prefilled syringes): 10 mg/0.4 mL.
Transdermal patch: 3.1 mg/24 hr.
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