Aprepitant by is a Prescription medication manufactured, distributed, or labeled by Sandoz Inc. Drug facts, warnings, and ingredients follow.
Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist, indicated:
Limitations of Use (1.3)
Recommended Dosage for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) (2.1)
Recommended Dosage for PONV (2.2)
Administration (2.4)
Aprepitant Capsules, USP: 40 mg; 80 mg; 125 mg (3)
Most common adverse reactions are (6.1):
Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)
PONV
To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc., at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See Full Prescribing Information for a list of clinically significant drug interactions. (4, 5.1, 5.2, 5.3, 7.1, 7.2)
Pediatric use information is approved for Merck Sharp & Dohme Corp.’s EMEND® (aprepitant) capsules. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that information.
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 6/2017
Aprepitant capsules, in combination with other antiemetic agents, are indicated for the prevention of:
Pediatric use information is approved for Merck Sharp & Dohme Corp.’s EMEND® (aprepitant) capsules. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that information.
Aprepitant capsules are indicated in adults for the prevention of postoperative nausea and vomiting.
Adults
The recommended oral dosage of aprepitant capsules, dexamethasone, and a 5-HT3 antagonist in adults for the prevention of nausea and vomiting associated with administration of HEC or MEC is shown in Table 1 or Table 2, respectively.
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Population |
Day1 |
Day 2 |
Day 3 |
Day 4 |
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Aprepitant capsules* |
Adults |
125 mg orally |
80 mg orally |
80 mg orally |
none |
Dexamethasone† |
Adults |
12 mg orally |
8 mg orally |
8 mg orally |
8 mg orally |
5-HT3 antagonist |
Adults |
See selected 5-HT3 antagonist prescribing information for the recommended dosage |
none |
none |
none |
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Population |
Day1 |
Day 2 |
Day 3 |
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Aprepitant capsules* |
Adults |
125 mg orally |
80 mg orally |
80 mg orally |
Dexamethasone† |
Adults |
12 mg orally |
none |
none |
5-HT3 antagonist |
Adults |
See the selected 5-HT3 antagonist prescribing information for recommended dosage |
none |
none |
Pediatric use information is approved for Merck Sharp & Dohme Corp.’s EMEND® (aprepitant) capsules. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that information.
Aprepitant Capsules, USP:
Aprepitant is contraindicated in patients:
Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4.
See Table 10 and Table 11 for a listing of potentially significant drug interactions [see Drug Interactions (7.1, 7.2)].
Coadministration of aprepitant with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in International Normalized Ratio (INR) of prothrombin time [see Clinical Pharmacology (12.3)]. Monitor the INR in patients on chronic warfarin therapy in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of aprepitant with each chemotherapy cycle, or following administration of a single 40-mg dose of aprepitant for the prevention of postoperative nausea and vomiting [see Drug Interactions (7.1)].
Upon coadministration with aprepitant, the efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of aprepitant [see Clinical Pharmacology (12.3)]. Advise patients to use alternative or back-up methods of contraception during treatment with aprepitant and for 1 month following the last dose of aprepitant [see Drug Interactions (7.1), Use in Specific Populations (8.3)].].
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.
The overall safety of aprepitant was evaluated in approximately 6,800 individuals.
Adverse Reactions in Adults in the Prevention of Nausea and Vomiting Associated with HEC and MEC
In 2 active-controlled, double-blind clinical trials in patients receiving highly emetogenic chemotherapy (HEC) (Studies 1 and 2), aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) was compared to ondansetron and dexamethasone alone (standard therapy) [see Clinical Studies (14.1)].
In 2 active-controlled clinical trials in patients receiving moderately emetogenic chemotherapy (MEC) (Studies 3 and 4), aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) was compared to ondansetron and dexamethasone alone (standard therapy) [see Clinical Studies (14.2)].The most common adverse reaction reported in patients who received MEC in pooled Studies 3 and 4 was dyspepsia (6% versus 4%).
Across these 4 studies there were 1412 patients treated with the aprepitant regimen during Cycle 1 of chemotherapy and 1099 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy. The most common adverse reactions reported in patients who received HEC and MEC in pooled Studies 1, 2, 3 and 4 are listed in Table 5.
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Aprepitant, ondansetron, and dexamethasone† (N=1412) |
Ondansetron and dexamethasone‡ (N=1396) |
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fatigue |
13% |
12% |
diarrhea |
9% |
8% |
asthenia |
7% |
6% |
dyspepsia |
7% |
5% |
abdominal pain |
6% |
5% |
hiccups |
5% |
3% |
white blood cell count decreased |
4% |
3% |
dehydration |
3% |
2% |
alanine aminotransferase increased |
3% |
2% |
In a pooled analysis of the HEC and MEC studies, less common adverse reactions reported in patients treated with the aprepitant regimen are listed in Table 6.
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Infection and Infestations |
oral candidiasis, pharyngitis |
Blood and the Lymphatic System Disorders |
anemia, febrile neutropenia, neutropenia, thrombocytopenia |
Metabolism and Nutrition Disorders |
decreased appetite, hypokalemia |
Psychiatric Disorders |
anxiety |
Nervous System Disorders |
dizziness, dysgeusia, peripheral neuropathy |
Cardiac Disorders |
palpitations |
Vascular Disorders |
flushing, hot flush |
Respiratory, Thoracic and Mediastinal Disorders |
cough, dyspnea, oropharyngeal pain |
Gastrointestinal Disorders |
dry mouth, eructation, flatulence, gastritis, gastroesophageal reflux disease, nausea, vomiting |
Skin and Subcutaneous Tissue Disorders |
alopecia, hyperhidrosis, rash |
Musculoskeletal and Connective Tissue Disorders |
musculoskeletal pain |
General Disorders and Administration Site Condition |
edema peripheral, malaise |
Investigations |
aspartate aminotransferase increased, blood alkaline phosphatase increased, blood sodium decreased, blood urea increased, proteinuria, weight decreased |
In an additional active-controlled clinical study in 1169 patients receiving aprepitant and HEC, the adverse reactions were generally similar to that seen in the other HEC studies with aprepitant.
In another CINV study, Stevens-Johnson syndrome was reported as a serious adverse reaction in a patient receiving the aprepitant regimen with cancer chemotherapy.
Adverse reactions in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were generally similar to that observed in Cycle 1.
Adverse Reactions in Adult Patients in the Prevention of PONV
In 2 active-controlled, double-blind clinical studies in patients receiving general anesthesia (Studies 7 and 8), 40-mg oral aprepitant was compared to 4-mg intravenous ondansetron [see Clinical Studies (14.4)].
There were 564 patients treated with aprepitant and 538 patients treated with ondansetron.
The most common adverse reactions reported in patients treated with aprepitant for PONV in pooled Studies 7 and 8 are listed in Table 8.
Aprepitant 40 mg (N = 564) |
Ondansetron (N = 538) |
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*Reported in ≥3% of patients treated with the Aprepitant 40 mg and at a greater incidence than ondansetron.
In a pooled analysis of PONV studies, less common adverse reactions reported in patients treated with aprepitant are listed in Table 9.
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*Reported in >0.5% of patients treated with aprepitant and at a greater incidence than ondansetron
In addition, two serious adverse reactions were reported in PONV clinical studies in patients taking a higher than recommended dose of aprepitant: one case of constipation, and one case of sub-ileus.
Other Studies
Angioedema and urticaria were reported as serious adverse reactions in a patient receiving aprepitant in a non-CINV/non-PONV study (aprepitant is only approved in the CINV and PONV populations).
The following adverse reactions have been identified during post-approval use of aprepitant. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and subcutaneous tissue disorders
Pruritus, rash, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis.
Immune system disorders
Hypersensitivity reactions including anaphylactic reactions [seeContraindications (4)].
Nervous system disorders
Ifosfamide-induced neurotoxicity reported after aprepitant and ifosfamide coadministration.
Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 [see Clinical Pharmacology (12.3)].
Aprepitant acts as a moderate inhibitor of CYP3A4 when administered as a 3-day regimen (125-mg/80-mg/80-mg) and can increase plasma concentrations of concomitant drugs that are substrates for CYP3A4. Aprepitant acts as a weak inhibitor when administered as a single 40-mg dose and has not been shown to alter the plasma concentrations of concomitant drugs that are primarily metabolized through CYP3A4. Some substrates of CYP3A4 are contraindicated with aprepitant [see Contraindications (4)]. Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 10.
Table 10 Effects of Aprepitant on the Pharmacokinetics of Other Drugs
CYP3A4 Substrates |
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Table 11 Effects of Other Drugs on Pharmacokinetics of Aprepitant
Moderate to Strong CYP3A4 Inhibitors |
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Risk Summary
There are insufficient data on use of aprepitant in pregnant women to inform a drug associated risk. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug levels (AUC) approximately 1.5 times the adult human exposure at the 125-mg/80-mg/80-mg aprepitant regimen [see Data].
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
In embryofetal development studies in rats and rabbits, aprepitant was administered during the period of organogenesis at oral doses up to 1000 mg/kg twice daily in rats and up to the maximum tolerated dose of 25 mg/kg/day in rabbits. No embryofetal lethality or malformations were observed at any dose levels in either species. The exposures (AUC) in pregnant rats at 1000 mg/kg twice daily and in pregnant rabbits at 125 mg/kg/day were approximately 1.5 times the adult exposure at the 125-mg/80‑mg/80-mg aprepitant regimen. Aprepitant crosses the placenta in rats and rabbits.
Lactation studies have not been conducted to assess the presence of aprepitant in human milk, the effects on the breastfed infant, or the effects on milk production. Aprepitant is present in rat milk. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for aprepitant and any potential adverse effects on the breastfed infant from aprepitant or from the underlying maternal condition.
Contraception
Upon administration of aprepitant, the efficacy of hormonal contraceptives may be reduced. Advise females of reproductive potential using hormonal contraceptives to use an effective alternative or back-up non-hormonal contraceptive (such as condoms and spermicides) during treatment with aprepitant and for 1 month following the last dose [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Prevention of Nausea and Vomiting Associated with HEC or MEC
The safety and effectiveness of aprepitant for the prevention of nausea and vomiting associated with HEC or MEC have not been established in patients less than 6 months.
Prevention of Postoperative Nausea and Vomiting (PONV)
The safety and effectiveness of aprepitant have not been established for the prevention of postoperative nausea and vomiting in pediatric patients.
Juvenile Animal Study
A study was conducted in young rats to evaluate the effects of aprepitant on growth and on neurobehavioral and sexual development. Rats were treated at oral doses up to the maximum feasible dose of 1000 mg/kg twice daily from the early postnatal period (Postnatal Day 10) through Postnatal Day 58. Slight changes in the onset of sexual maturation were observed in female and male rats; however, there were no effects on mating, fertility, embryonic-fetal survival, or histomorphology of the reproductive organs. There were no effects in neurobehavioral tests of sensory function, motor function, and learning and memory.
Pediatric use information is approved for Merck Sharp & Dohme Corp.’s EMEND® (aprepitant) capsules. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that information.
Of the 544 adult cancer patients treated with aprepitant in CINV clinical studies, 31% were aged 65 and over, while 5% were aged 75 and over. Of the 1120 adult cancer patients treated with aprepitant in PONV clinical studies, 7% were aged 65 and over, while 2% were aged 75 and over. Other reported clinical experience with aprepitant has not identified differences in responses between elderly and younger patients. In general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)].
The pharmacokinetics of aprepitant in patients with severe renal impairment and those with end stage renal disease (ESRD) requiring hemodialysis were similar to those of healthy subjects with normal renal function. No dosage adjustment is necessary for patients with any degree of renal impairment or for patients with ESRD undergoing hemodialysis.
The pharmacokinetics of aprepitant in patients with mild and moderate hepatic impairment were similar to those of healthy subjects with normal hepatic function. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 9). There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9). Therefore, additional monitoring for adverse reactions in these patients may be warranted when aprepitant is administered [see Clinical Pharmacology (12.3)].
No specific information is available on the treatment of overdosage.
Drowsiness and headache were reported in one patient who ingested 1440 mg of aprepitant (approximately 11 times the maximum recommended single dose).
In the event of overdose, aprepitant should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of aprepitant, drug-induced emesis may not be effective in cases of aprepitant overdosage.
Aprepitant is not removed by hemodialysis.
Aprepitant capsules, USP contain the active ingredient, aprepitant. Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist, an antiemetic agent, chemically described as 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one.
Its molecular formula is C23H21F7N4O3, and its structural formula is:
Aprepitant is a white to off-white crystalline solid, with a molecular weight of 534.43. It is practically insoluble in water. Aprepitant is sparingly soluble in ethanol and isopropyl acetate and slightly soluble in acetonitrile.
Each aprepitant capsule, USP for oral administration contains either 40 mg, 80 mg or 125 mg of aprepitant and the following inactive ingredients: hydroxypropyl cellulose, microcrystalline cellulose, sodium lauryl sulfate and sucrose.
The aprepitant capsule shell for 40 mg and 80 mg consists of gelatin and titanium dioxide.
The aprepitant capsule shell for 125 mg consists of FD&C Blue # 1, gelatin and titanium dioxide.
The capsule is printed with edible black pharmaceutical ink. The printing ink contains black iron oxide, propylene glycol and shellac.
Dissolution Test 2 is used.
Aprepitant is a 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, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).
Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that aprepitant augments the 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.
NK1 Receptor Occupancy
In two single-blind, multiple-dose, randomized, and placebo-controlled studies, healthy young men received oral aprepitant doses of 10 mg (N=2), 30 mg (N=3), 100 mg (N=3) or 300 mg (N=5) once daily (0.08, 0.24, 0.8, and 2.4 times the maximum recommended single dose, respectively) for 14 days with 2 or 3 subjects on placebo. Both plasma aprepitant concentration and NK1 receptor occupancy in the corpus striatum by positron emission tomography were evaluated, at predose and 24 hours after the last dose. At aprepitant plasma concentrations of ~10 ng/mL and ~100 ng/mL, the NK1 receptor occupancies were ~50% and ~90%, respectively. The oral aprepitant regimen for CINV produced mean trough plasma aprepitant concentrations greater than 500 ng/mL in adults, which would be expected to, based on the fitted curve with the Hill equation, result in greater than 95% brain NK1 receptor occupancy. However, the receptor occupancy for either CINV or PONV dosing regimen has not been determined. In addition, the relationship between NK1 receptor occupancy and the clinical efficacy of aprepitant has not been established.
Cardiac Electrophysiology
In a randomized, double-blind, positive-controlled, thorough QTc study, a single 200-mg dose of fosaprepitant had no effect on the QTc interval. Maximum aprepitant concentrations after a single 200-mg dose of fosaprepitant were 4- and 9-fold higher than that achieved with oral aprepitant 125 mg and 40 mg, respectively. QT prolongation with the oral aprepitant dosing regimens for CINV and PONV is not expected.
Absorption
Following oral administration of a single 40-mg dose of aprepitant in the fasted state, mean area under the plasma concentration-time curve (AUC0-∞) was 7.8 mcghr/mL and mean peak plasma concentration (Cmax) was 0.7 mcg/mL, occurring at approximately 3 hours postdose (Tmax). The absolute bioavailability at the 40-mg dose has not been determined.
Following oral administration of a single 125-mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 and 3, the AUC0-24hr was approximately 19.6 mcghr/mL and 21.2 mcghr/mL on Day 1 and Day 3, respectively. The Cmax of 1.6 mcg/mL and 1.4 mcg/mL were reached in approximately 4 hours (Tmax) on Day 1 and Day 3, respectively. At the dose range of 80 to 125 mg, the mean absolute oral bioavailability of aprepitant is approximately 60 to 65%. Oral administration of the capsule with a standard high-fat breakfast had no clinically meaningful effect on the bioavailability of aprepitant.
The pharmacokinetics of aprepitant were non-linear across the clinical dose range. In healthy young adults, the increase in AUC0-∞ was 26% greater than dose proportional between 80-mg and 125-mg single doses administered in the fed state.
Distribution
Aprepitant is greater than 95% bound to plasma proteins. The mean apparent volume of distribution at steady state (Vdss) was approximately 70 L in humans.
Aprepitant crosses the blood brain barrier in humans [see Clinical Pharmacology (12.1)].
Elimination
Metabolism
Aprepitant undergoes extensive metabolism. In vitro studies using human liver microsomes indicate that aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19. Metabolism is largely via oxidation at the morpholine ring and its side chains. No metabolism by CYP2D6, CYP2C9, or CYP2E1 was detected. In healthy young adults, aprepitant accounts for approximately 24% of the radioactivity in plasma over 72 hours following a single oral 300-mg dose of [14C]-aprepitant (2.4 times the maximum recommended dose), indicating a substantial presence of metabolites in the plasma. Seven metabolites of aprepitant, which are only weakly active, have been identified in human plasma.
Excretion
Following administration of a single intravenous 100-mg dose of [14C]-aprepitant prodrug to healthy subjects, 57% of the radioactivity was recovered in urine and 45% in feces. A study was not conducted with radiolabeled capsule formulation. The results after oral administration may differ.
Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted. The apparent plasma clearance of aprepitant ranged from approximately 62 to 90 mL/min. The apparent terminal half-life ranged from approximately 9 to 13 hours.
Specific Populations
Age: Geriatric Population
Following oral administration of a single 125-mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 through 5 (2 additional days of dosing compared to the recommended duration), the AUC0-24hr of aprepitant was 21% higher on Day 1 and 36% higher on Day 5 in elderly (65 years and older) relative to younger adults. The Cmax was 10% higher on Day 1 and 24% higher on Day 5 in elderly relative to younger adults. These differences are not considered clinically meaningful [see Use in Specific Populations (8.5)].
Sex
Following oral administration of a single dose of aprepitant ranging from 40 mg to 375 mg (3 times the maximum recommended dose), the AUC0-24hr and Cmax are 9% and 17% higher in females as compared with males. The half-life of aprepitant is 25% lower in females as compared with males and Tmax occurs at approximately the same time. These differences are not considered clinically meaningful.
Race/Ethnicity
Following oral administration of a single dose of aprepitant ranging from 40 mg to 375 mg (3 times the maximum recommended dose), the AUC0-24hr and Cmax are approximately 27% and 19% higher in Hispanics as compared with Caucasians. The AUC0-24hr and Cmax were 74% and 47% higher in Asians as compared to Caucasians. There was no difference in AUC0-24hr or Cmax between Caucasians and Blacks. These differences are not considered clinically meaningful.
Renal Impairment
A single 240-mg dose of aprepitant (approximately 1.9 times the maximum recommended dose) was administered to patients with severe renal impairment (creatinine clearance less than 30 mL/min/1.73 m2 as measured by 24-hour urinary creatinine clearance) and to patients with end stage renal disease (ESRD) requiring hemodialysis.
In patients with severe renal impairment, the AUC0-∞ of total aprepitant (unbound and protein bound) decreased by 21% and Cmax decreased by 32%, relative to healthy subjects (creatinine clearance greater than 80 mL/min estimated by Cockcroft-Gault method). In patients with ESRD undergoing hemodialysis, the AUC0-∞ of total aprepitant decreased by 42% and Cmax decreased by 32%. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC of pharmacologically active unbound drug was not significantly affected in patients with renal impairment compared with healthy subjects. Hemodialysis conducted 4 or 48 hours after dosing had no significant effect on the pharmacokinetics of aprepitant; less than 0.2% of the dose was recovered in the dialysate [see Use in Specific Populations (8.6)].
Hepatic Impairment
Following administration of a single 125-mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 and 3 to patients with mild hepatic impairment (Child-Pugh score 5 to 6), the AUC0-24hr of aprepitant was 11 % lower on Day 1 and 36% lower on Day 3, as compared with healthy subjects given the same regimen. In patients with moderate hepatic impairment (Child-Pugh score 7 to 9), the AUC0-24hr of aprepitant was 10% higher on Day 1 and 18% higher on Day 3, as compared with healthy subjects given the same regimen. These differences in AUC0-24hr are not considered clinically meaningful .There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9) [see Use in Specific Populations(8.7)].
Body Mass Index (BMI)
For every 5 kg/m2 increase in BMI, AUC0-24hr and Cmax of aprepitant decrease by 9% and 10%. BMI of subjects in the analysis ranged from 18 kg/m2 to 36 kg/m2 . This change is not considered clinically meaningful.
Pediatric use information is approved for Merck Sharp & Dohme Corp.’s EMEND® (aprepitant) capsules. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that information.
Drug Interactions Studies
Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Aprepitant is unlikely to interact with drugs that are substrates for the P-glycoprotein transporter.
Effects of Aprepitant on the Pharmacokinetics of Other Drugs
CYP3A4 substrates (i.e., midazolam)
Interactions between aprepitant and coadministered midazolam are listed in Table 12 (increase is indicated as “↑”, decrease as “↓”, no change as “↔”).
Table 12 Pharmacokinetic Interaction Data for Aprepitant and Coadministered Midazolam
Dosage of Aprepitant |
Dosage of Midazolam |
Observed Drug Interactions |
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A difference of less than 2-fold increase of midazolam AUC is not considered clinically important.
Corticosteroids
Dexamethasone
Aprepitant, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 through 5, coadministered with 20-mg dexamethasone on Day 1 and 8-mg dexamethasone on Days 2 through 5, increased the AUC of dexamethasone by 2.2-fold on Days 1 and 5 [see Dosage and Administration (2.1)]. A single dose of aprepitant (40 mg) when coadministered with a single dose of dexamethasone 20 mg, increased the AUC of dexamethasone by 1.45-fold, which is not considered clinically significant.
Methylprednisolone
Aprepitant, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of methylprednisolone by 1.34-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was coadministered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3. Although the concomitant administration of methylprednisolone with the single 40-mg dose of aprepitant has not been studied, a single 40-mg dose of aprepitant produces a weak inhibition of CYP3A4 (based on midazolam interaction study) and it is not expected to alter the plasma concentrations of methylprednisolone to a clinically significant degree.
Chemotherapeutic agents
Docetaxel
In a pharmacokinetic study, aprepitant (125-mg/80-mg regimen) did not influence the pharmacokinetics of docetaxel.
Vinorelbine
In a pharmacokinetic study, aprepitant (125-mg/80-mg regimen) did not influence the pharmacokinetics of vinorelbine to a clinically significant degree.
Oral contraceptives
When aprepitant was administered as a 3-day regimen (125-mg/80-mg/80-mg) with ondansetron and dexamethasone, and coadministered with an oral contraceptive containing ethinyl estradiol and norethindrone, the trough concentrations of both ethinyl estradiol and norethindrone were reduced by as much as 64% for 3 weeks post-treatment [see Warnings and Precautions (5.3)].
When a daily dosage of an oral contraceptive containing ethinyl estradiol and norgestimate was administered on Days 1 through 21, and aprepitant 40 mg was given on Day 8, the AUC of ethinyl estradiol decreased by 4% and by 29% on Day 8 and Day 12, respectively, while the AUC of norelgestromin increased by 18% on Day 8 and decreased by 10% on Day 12. In addition, the trough concentrations of ethinyl estradiol and norelgestromin on Days 8 through 21 were generally lower following coadministration of the oral contraceptive with aprepitant 40 mg on Day 8 compared to the trough levels following administration of the oral contraceptive alone [see Drug Interactions(7.1)].
CYP2C9 substrates (e.g., warfarin)
A single 125-mg dose of aprepitant was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilized on chronic warfarin therapy. Although there was no effect of aprepitant on the plasma AUC of R(+) or S(-) warfarin determined on Day 3, there was a 34% decrease in S(-) warfarin trough concentration accompanied by a 14% decrease in the prothrombin time (reported as International Normalized Ratio or INR) 5 days after completion of dosing with aprepitant [see Drug Interactions(7.1)].
Tolbutamide
Aprepitant, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of tolbutamide by 23% on Day 4, 28% on Day 8, and 15% on Day 15, when a single dose of tolbutamide 500 mg was administered prior to the administration of the 3-day regimen of aprepitant and on Days 4, 8, and 15. This effect was not considered clinically important.
Aprepitant, when given as a 40-mg single dose on Day 1, decreased the AUC of tolbutamide by 8% on Day 2, 16% on Day 4, 15% on Day 8, and 10% on Day 15, when a single dose of tolbutamide 500 mg was administered prior to the administration of aprepitant 40 mg and on Days 2, 4, 8, and 15. This effect was not considered significant.
P-glycoprotein substrates
Aprepitant is unlikely to interact with drugs that are substrates for the P‑glycoprotein transporter, as demonstrated by the lack of interaction of aprepitant with digoxin in a clinical drug interaction study.
5-HT3 antagonists
In clinical drug interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of dolasetron).
Effect of Other Drugs on the Pharmacokinetics of Aprepitant
Ketoconazole
When a single 125-mg dose of aprepitant was administered on Day 5 of a 10-day regimen of 400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold [see Drug Interactions (7.2)].
Rifampin
When a single 375-mg dose of aprepitant (3 times the maximum recommended dose) was administered on Day 9 of a 14-day regimen of 600 mg/day of rifampin, a strong CYP3A4 inducer, the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased approximately 3-fold [see Drug Interactions (7.2)].
Diltiazem
In patients with mild to moderate hypertension, administration of aprepitant once daily, as a tablet formulation comparable to 230 mg of the capsule formulation (approximately 1.8 times the recommended dose), with diltiazem 120 mg 3 times daily for 5 days, resulted in a 2-fold increase of aprepitant AUC and a simultaneous 1.7-fold increase of diltiazem AUC. These pharmacokinetic effects did not result in clinically meaningful changes in ECG, heart rate or blood pressure beyond those changes induced by diltiazem alone [see Drug Interactions (7.2)].
Paroxetine
Coadministration of once daily doses of aprepitant, as a tablet formulation comparable to 85 mg or 170 mg of the capsule formulation (approximately 0.7 and 1.4 times the maximum recommended dose), with paroxetine 20 mg once daily, resulted in a decrease in AUC by approximately 25% and Cmax by approximately 20% of both aprepitant and paroxetine. This effect was not considered clinically important.
Carcinogenesis
Carcinogenicity studies were conducted in Sprague-Dawley rats and in CD-1 mice for 2 years. In the rat carcinogenicity studies, animals were treated with oral doses ranging from 0.05 to 1000 mg/kg twice daily. The highest dose produced a systemic exposure to aprepitant (AUC) of 0.7 to 1.6 times the adult human exposure at the 125-mg/80-mg/80-mg aprepitant regimen. Treatment with aprepitant at doses of 5 to 1000 mg/kg twice daily caused an increase in the incidences of thyroid follicular cell adenomas and carcinomas in male rats. In female rats, it produced hepatocellular adenomas at 5 to 1000 mg/kg twice daily and hepatocellular carcinomas and thyroid follicular cell adenomas at 125 to 1000 mg/kg twice daily. In the mouse carcinogenicity studies, the animals were treated with oral doses ranging from 2.5 to 2000 mg/kg/day. The highest dose produced a systemic exposure of about 2.8 to 3.6 times the adult human exposure at the 125-mg/80-mg/80-mg aprepitant regimen. Treatment with aprepitant produced skin fibrosarcomas at 125 and 500 mg/kg/day doses in male mice.
Mutagenesis
Aprepitant was not genotoxic in the Ames test, the human lymphoblastoid cell (TK6) mutagenesis test, the rat hepatocyte DNA strand break test, the Chinese hamster ovary (CHO) cell chromosome aberration test and the mouse micronucleus test.
Impairment of Fertility
Aprepitant did not affect the fertility or general reproductive performance of male or female rats at doses up to the maximum feasible dose of 1000 mg/kg twice daily (providing exposure in male rats lower than the exposure at the recommended adult human dose and exposure in female rats at about 1.6 times the adult human exposure at the 125-mg/80-mg/80-mg aprepitant regimen).
Oral administration of aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) has been shown to prevent acute and delayed nausea and vomiting associated with HEC including high-dose cisplatin, and nausea and vomiting associated with MEC.
In Studies 1 and 2, both multicenter, randomized, parallel, double-blind, controlled clinical studies in adults, aprepitant in combination with ondansetron and dexamethasone was compared with standard therapy (ondansetron and dexamethasone alone) in patients receiving a chemotherapy regimen that included cisplatin greater than 50 mg/m2 (mean cisplatin dose = 80.2 mg/m2). See Table 13.
In these studies, 95% of the patients in the aprepitant group received a concomitant chemotherapeutic agent in addition to protocol-mandated cisplatin. The most common chemotherapeutic agents and the number of aprepitant patients exposed follows: etoposide (106), fluorouracil (100), gemcitabine (89), vinorelbine (82), paclitaxel (52), cyclophosphamide (50), doxorubicin (38), docetaxel (11).
Of the 550 patients who were randomized to receive the aprepitant regimen, 42% were women, 58% men, 59% White, 3% Asian, 5% Black, 12% Hispanic American, and 21% Multi-Racial. The aprepitant-treated patients in these clinical studies ranged from 14 to 84 years of age, with a mean age of 56 years. A total of 170 patients were 65 years or older, with 29 patients being 75 years or older.
Table 13 HEC Treatment Regimens – Studies 1 and 2**
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5-HT3 antagonist‡ |
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5-HT3 antagonist‡ |
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The antiemetic activity of aprepitant was evaluated during the acute phase (0 to 24 hours post-cisplatin treatment), the delayed phase (25 to 120 hours post-cisplatin treatment) and overall (0 to 120 hours post-cisplatin treatment) in Cycle 1. Efficacy was based on evaluation of the following endpoints in which emetic episodes included vomiting, retching, or dry heaves:
Primary endpoint
Other prespecified endpoints
A summary of the key study results from each individual study analysis is shown in Table 14. In both studies, a statistically significantly higher proportion of patients receiving the aprepitant regimen in Cycle 1 had a complete response in the overall phase (primary endpoint), compared with patients receiving standard therapy. A statistically significant difference in complete response in favor of the aprepitant regimen was also observed when the acute phase and the delayed phase were analyzed separately.
Table 14 Percent of Patients Receiving HEC Responding by Treatment Group and Phase — Cycle 1
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Aprepitant Regimen (N=260)* % |
Standard Therapy (N=261)*
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Aprepitant Regimen (N=261)*
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Standard Therapy (N=263)*
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p-Value |
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PRIMARY ENDPOINT |
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Visual analogue scale (VAS) score range: 0 mm=no nausea; 100 mm=nausea as bad as it could be. |
In both studies, the estimated time to first emesis after initiation of cisplatin treatment was longer with the aprepitant regimen, and the incidence of first emesis was reduced in the aprepitant regimen group compared with standard therapy group as depicted in the Kaplan-Meier curves in Figure 1.
Figure 1 Percent of Patients Receiving HEC Who Remain Emesis Free Over Time – Cycle 1
Additional Patient-Reported Outcomes
The impact of nausea and vomiting on patients’ daily lives was assessed in Cycle 1 of both studies using the Functional Living Index–Emesis (FLIE), a validated nausea- and vomiting-specific patient-reported outcome measure. Minimal or no impact of nausea and vomiting on patients’ daily lives is defined as a FLIE total score greater than 108. In each of the 2 studies, a higher proportion of patients receiving the aprepitant regimen reported minimal or no impact of nausea and vomiting on daily life (Study 1: 74% versus 64%; Study 2: 75% versus 64%).
Multiple-Cycle Extension
In the same 2 clinical studies, patients continued into the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy. The proportion of patients with no emesis and no significant nausea by treatment group at each cycle is depicted in Figure 2. Antiemetic effectiveness for the patients receiving the aprepitant regimen was maintained throughout repeat cycles for those patients continuing in each of the multiple cycles.
Aprepitant was studied in two randomized, double-blind, parallel-group studies (Studies 3 and 4) in adult patients receiving MEC.
In Study 3, in breast cancer patients, aprepitant in combination with ondansetron and dexamethasone was compared with standard therapy (ondansetron and dexamethasone) in patients receiving a MEC regimen that included cyclophosphamide 750 to 1500 mg/m2; or cyclophosphamide 500 to 1500 mg/m2 and doxorubicin (less than or equal to 60 mg/m2) or epirubicin (less than or equal to 100 mg/m2). See Table 15.
In this study, the most common combinations were cyclophosphamide + doxorubicin (61%); and cyclophosphamide + epirubicin + fluorouracil (22%).
Of the 438 patients who were randomized to receive the aprepitant regimen, 99.5% were women. Of these, approximately 80% were White, 8% Black, 8% Asian, 4% Hispanic, and less than 1% Other. The aprepitant-treated patients in this clinical study ranged from 25 to 78 years of age, with a mean age of 53 years; 70 patients were 65 years or older, with 12 patients being over 74 years.
Table 15 MEC Treatment Regimens – Studies 3 and 4**
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CINV Aprepitant Regimen |
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12 mg† |
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8 mg x 2 doses‡ |
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CINV Standard Therapy |
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20 mg† |
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8 mg x 2 doses‡ |
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The antiemetic activity of aprepitant was evaluated based on the following endpoints in which emetic episodes included vomiting, retching, or dry heaves:
Primary endpoint
Other prespecified endpoints
A summary of the key results from Study 3 is shown in Table 16. In Study 3, a statistically significantly (p=0.015) higher proportion of patients receiving the aprepitant regimen (51%) in Cycle 1 had a complete response (primary endpoint) during the overall phase compared with patients receiving standard therapy (42%). The difference between treatment groups was primarily driven by the “No Emesis Endpoint”, a principal component of this composite primary endpoint. In addition, a higher proportion of patients receiving the aprepitant regimen in Cycle 1 had a complete response during the acute (0-24 hours) and delayed (25 to 120 hours) phases compared with patients receiving standard therapy; however, the treatment group differences failed to reach statistical significance, after multiplicity adjustments.
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ENDPOINTS |
Aprepitant Regimen (N=433)* % |
Standard Therapy (N=424)* % |
p-Value |
PRIMARY ENDPOINT† |
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Complete Response |
51 |
42 |
0.015 |
OTHER PRESPECIFIED ENDPOINTS† |
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No Emesis |
76 |
59 |
NS‡ |
No Nausea |
33 |
33 |
NS |
No Significant Nausea |
61 |
56 |
NS |
No Rescue Therapy |
59 |
56 |
NS |
Complete Protection |
43 |
37 |
NS |
Additional Patient-Reported Outcomes
In Study 3, in patients receiving MEC, the impact of nausea and vomiting on patients’ daily lives was assessed in Cycle 1 using the FLIE. A higher proportion of patients receiving the aprepitant regimen reported minimal or no impact on daily life (64% versus 56%). This difference between treatment groups was primarily driven by the “No Vomiting Domain” of this composite endpoint.
Multiple-Cycle Extension
In Study 3, patients receiving MEC were permitted to continue into the Multiple-Cycle extension of the study for up to 3 additional cycles of chemotherapy. The antiemetic effect for patients receiving the aprepitant regimen was maintained during all cycles.
In Study 4, aprepitant in combination with ondansetron and dexamethasone was compared with a standard therapy (ondansetron and dexamethasone alone) in patients receiving a MEC regimen that included any intravenous dose of oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin; cyclophosphamide intravenous (less than 1500 mg/m2); or cytarabine intravenous (greater than 1 g/m2). See Table 15. Patients receiving the aprepitant regimen were receiving chemotherapy for a variety of tumor types including 50% with breast cancer, 21% with gastrointestinal cancers including colorectal cancer, 13% with lung cancer and 6% with gynecological cancers.
Of the 430 patients who were randomized to receive the aprepitant regimen, 76% were women and 24% were men. The distribution by race was 67% White, 6% Black or African American, 11% Asian, and 12% multiracial. Classified by ethnicity, 36% were Hispanic and 64% were non-Hispanic. The aprepitant-treated patients in this clinical study ranged from 22 to 85 years of age, with a mean age of 57 years; approximately 59% of the patients were 55 years or older with 32 patients being over 74 years.
The antiemetic activity of aprepitant was evaluated based on no vomiting (with or without rescue therapy) in the overall period (0 to 120 hours post-chemotherapy) and complete response (defined as no vomiting and no use of rescue therapy) in the overall period.
A summary of the key results from Study 4 is shown in Table 17. In Study 4, a statistically significantly higher proportion of patients receiving the aprepitant regimen (76%) in Cycle 1 had no vomiting during the overall phase compared with patients receiving standard therapy (62%). In addition, a higher proportion of patients receiving the aprepitant regimen (69%) in Cycle 1 had a complete response in the overall phase (0-120 hours) compared with patients receiving standard therapy (56%). In the acute phase (0 to 24 hours following initiation of chemotherapy), a higher proportion of patients receiving aprepitant compared to patients receiving standard therapy were observed to have no vomiting (92% and 84%, respectively) and complete response (89% and 80%, respectively). In the delayed phase (25 to 120 hours following initiation of chemotherapy), a higher proportion of patients receiving aprepitant compared to patients receiving standard therapy were observed to have no vomiting (78% and 67%, respectively) and complete response (71% and 61%, respectively).
In a subgroup analysis by tumor type, a numerically higher proportion of patients receiving aprepitant were observed to have no vomiting and complete response compared to patients receiving standard therapy. For sex, the difference in complete response rates between the aprepitant and standard regimen groups was 14% in females (64.5% and 50.3%, respectively) and 4% in males (82.2% and 78.2%, respectively) during the overall phase. A similar difference for sex was observed for the no vomiting endpoint.
Table 17 Percent of Patients Receiving MEC Responding by Treatment Group — Cycle 1 of Study 4
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Pediatric use information is approved for Merck Sharp & Dohme Corp.’s EMEND® (aprepitant) capsules. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that information.
In two multicenter, randomized, double-blind, active comparator-controlled, parallel-group clinical studies (Studies 7 and 8), aprepitant was compared with ondansetron for the prevention of postoperative nausea and vomiting in 1,658 patients undergoing open abdominal surgery. These two studies were of similar design; however, they differed in terms of study hypothesis, efficacy analyses and geographic location. Study 7 was a multinational study including the U.S., whereas, Study 8 was conducted entirely in the U.S.
In the two studies, patients were randomized to receive 40-mg aprepitant, 125-mg aprepitant, or 4-mg ondansetron as a single dose. Aprepitant was given orally with 50 mL of water 1 to 3 hours before anesthesia. Ondansetron was given intravenously immediately before induction of anesthesia. A comparison between the aprepitant 125-mg dose did not demonstrate any additional clinical benefit over the 40-mg dose and is not a recommended dosage regimen [see Dosage and Administration (2.2)].
Of the 564 patients who received 40-mg aprepitant, 92% were women and 8% were men; of these, 58% were White, 13% Hispanic American, 7% Multi-Racial, 14% Black, 6% Asian, and 2% Other. The age of patients treated with 40-mg aprepitant ranged from 19 to 84 years, with a mean age of 46.1 years. 46 patients were 65 years or older, with 13 patients being 75 years or older.
The antiemetic activity of aprepitant was evaluated during the 0 to 48 hour period following the end of surgery.
Efficacy measures in Study 7 included
A closed testing procedure was applied to control the type I error for the primary endpoints.
The results of the primary and secondary endpoints for 40-mg aprepitant and 4-mg ondansetron are described in Table 20:
Table 20 Response Rates for Select Efficacy Endpoints (Modified-Intention-to-Treat Population) – Study 7
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Δ |
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12.6% |
2.1 |
P<0.001† |
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8.8% |
1.4 |
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8.8% |
1.4 |
LB=1.02‡ |
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15.2% |
2.3 |
P<0.001§ |
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In Study 7, the use of aprepitant did not affect the time to first use of rescue medication when compared to ondansetron. However, compared to the ondansetron group, use of aprepitant delayed the time to first vomiting, as depicted in Figure 3.
Efficacy measures in Study 8 included:
Study 8 failed to satisfy its primary hypothesis that aprepitant is superior to ondansetron in the prevention of PONV as measured by the proportion of patients with complete response in the 24 hours following end of surgery.
The study demonstrated that 40-mg aprepitant had a clinically meaningful effect with respect to the secondary endpoint "no vomiting" during the first 24 hours after surgery and was associated with a 16% improvement over ondansetron for the no vomiting endpoint.
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Analysis |
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111/248 (44.8) |
2.5% |
1.1 |
0.61 |
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104/246 (42.3) | |||
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223/248 (89.9) |
16.3% |
3.2 |
<0.001† |
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181/246 (73.6) | |||
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112/248 (45.2) |
-0.7% |
1 |
0.83 |
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113/246 (45.9) | |||
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209/247 (84.6) |
17.7% |
2.7 |
<0.001* |
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164/245 (66.9) | |||
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Aprepitant capsules, USP 40 mg, are hard gelatin capsules with opaque white cap and opaque white body containing white to off white colored pellets. The cap is imprinted with ‘SZ’ and the body is imprinted with ‘525’ in black ink
Aprepitant capsules, USP 80 mg, are hard gelatin capsules with opaque white cap and clear transparent body containing white to off white colored pellets. The cap is imprinted with ‘SZ’ and the body is imprinted with ‘528’ in black ink.
Aprepitant capsules, USP 125 mg, are hard gelatin capsules with opaque light blue cap and opaque white body containing white to off white colored pellets. The cap is imprinted with ‘SZ’ and the body is imprinted with ‘529’ in black ink.
Storage
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Advise the patient to read the FDA-Approved patient labeling (Patient Information).
Hypersensitivity Reactions
Advise patients that hypersensitivity reactions, including anaphylaxis, have been reported in patients taking aprepitant. Advise patients to stop taking aprepitant and seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction, such as hives, rash and itching, skin peeling or sores, or difficulty in breathing or swallowing.
Drug Interactions
Advise patients to discuss all medications they are taking, including other prescription, non‑prescription medication or herbal products [see Contraindications (4), Warnings and Precautions (5.1)].
Warfarin
Instruct patients on chronic warfarin therapy to follow instructions from their healthcare provider regarding blood draws to monitor their INR during the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of aprepitant with each chemotherapy cycle, or following administration of a single 40-mg dose of aprepitant for the prevention of postoperative nausea and vomiting [see Warnings and Precautions (5.2)].
Hormonal Contraceptives
Advise patients that administration of aprepitant may reduce the efficacy of hormonal contraceptives. Instruct patients to use effective alternative or back-up methods of contraception (such as condoms and spermicides) during treatment with aprepitant and for 1 month following the last dose of aprepitant [see Warnings and Precautions (5.3), Use in Specific Populations (8.3)].
The brands listed are the registered trademarks of their respective owners and are not trademarks of Sandoz Inc.
Finished Drug Product Manufactured by
Lek Pharmaceuticals d.d.,
SI-1526 Ljubljana, Slovenia for
Sandoz Inc., Princeton, NJ 08540
Product of India
Rev.: June 2017
Aprepitant Capsules
(a-PRE-pi-tant)
Read this Patient Information before you start taking aprepitant and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.
What are aprepitant capsules?
Aprepitant is not used to treat nausea and vomiting that you already have. Aprepitant should not be used continuously for a long time (chronic use).
Who should not take aprepitant capsules?
Do not take aprepitant capsules if you:
Aprepitant capsules may affect the way other medicines work, and other medicines may affect how aprepitant works causing serious side effects.
Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of aprepitant capsules. For more information ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to Sandoz Inc., at 1-800-525-8747 or FDA at 1-800-FDA-1088.
Keep aprepitant capsules and all medicines out of the reach of children.
General information about the safe and effective use of aprepitant capsules
Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use aprepitant capsules for a condition for which it was not prescribed. Do not give aprepitant capsules to other people, even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for information about aprepitant capsules that is written for health professionals. For more information about aprepitant capsules call Sandoz Inc., at 1-800-525-8747.
What are the ingredients in aprepitant capsules?
Active ingredient: aprepitant
Inactive ingredients: hydroxypropyl cellulose, microcrystalline cellulose, sodium lauryl sulfate and sucrose.
The capsule shell for 40 mg and 80 mg contains gelatin and titanium dioxide. The capsule shell for 125 mg contains FD&C Blue # 1, gelatin and titanium dioxide. The capsule is printed with edible black pharmaceutical ink. The printing ink contains black iron oxide, propylene glycol and shellac.
Pediatric use information is approved for Merck Sharp & Dohme Corp.’s EMEND® (aprepitant) capsules. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that information.
The brands listed are the registered trademarks of their respective owners and are not trademarks of Sandoz Inc.
Finished Drug Product Manufactured by
Lek Pharmaceuticals d.d.,
Sl-1526 Ljubljana, Slovenia for
Sandoz Inc., Princeton, NJ 08540
Product of India
Rev.: June 2017
APREPITANT
aprepitant capsule |
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APREPITANT
aprepitant capsule |
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APREPITANT
aprepitant kit |
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APREPITANT
aprepitant capsule |
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Labeler - Sandoz Inc (005387188) |