1. Name Of The Medicinal Product
IVEMEND 115 mg powder for solution for infusion.
2. Qualitative And Quantitative Composition
Each vial contains fosaprepitant dimeglumine equivalent to 115 mg fosaprepitant. After reconstitution and dilution 1 ml of solution contains 1 mg fosaprepitant (see section 6.6).
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Powder for solution for infusion.
White to off-white amorphous powder.
4. Clinical Particulars
4.1 Therapeutic Indications
Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy in adults.
Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy in adults.
IVEMEND 115mg is given as part of a combination therapy (see section 4.2).
4.2 Posology And Method Of Administration
IVEMEND is a lyophilized prodrug of aprepitant containing polysorbate 80 (PS80) for intravenous administration. Aprepitant is available as capsules for oral administration.
Posology
IVEMEND (115 mg) may be substituted for aprepitant (125 mg) prior to chemotherapy, on Day 1 only of the chemotherapy induced nausea and vomiting (CINV) regimen as an infusion administered over 15 minutes (see section 6.6).
The 3-day CINV regimen includes IVEMEND (115 mg) 30 minutes prior to chemotherapy treatment or aprepitant (125 mg) PO once daily one hour prior to chemotherapy treatment on Day 1; aprepitant (80 mg) PO on Days 2 and 3; in addition to a corticosteroid and a 5-HT3 antagonist.
The following regimen is recommended, based on clinical studies with aprepitant, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy.
Highly Emetogenic Chemotherapy Regimen
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In clinical studies:
Aprepitant was administered orally 1 hour prior to chemotherapy treatment on Day 1 and in the morning on Days 2 and 3.
Dexamethasone was administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 to 4. The dose of dexamethasone was chosen to account for active substance interactions.
Ondansetron was administered intravenously 30 minutes prior to chemotherapy treatment on Day 1.
Moderately Emetogenic Chemotherapy Regimen
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In clinical studies:
Aprepitant was administered orally 1 hour prior to chemotherapy treatment on Day 1 and in the morning on Days 2 and 3.
Dexamethasone was administered 30 minutes prior to chemotherapy treatment on Day 1. The dose of dexamethasone was chosen to account for active substance interactions.
One 8 mg capsule of ondansetron was administered 30 to 60 minutes prior to chemotherapy treatment and one 8 mg capsule was administered 8 hours after first dose on Day 1.
Efficacy data on combination with other corticosteroids and 5-HT3 antagonists are limited. For additional information on the co-administration with corticosteroids, see section 4.5.
Refer to the Summary of Product Characteristics of co-administered antiemetic agents.
Elderly(
No dose adjustment is necessary for the elderly (see section 5.2)
Gender.
No dose adjustment is necessary based on gender (see section 5.2)
Renal Impairment
No dose adjustment is necessary for patients with renal impairment or for patients with end stage renal disease undergoing haemodialysis (see section 5.2).
Hepatic Impairment
No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment (see sections 4.4 and 5.2).
Children and adolescents
IVEMEND is not recommended for use in children below the age of 18 years of age due to insufficient data on safety and efficacy.
Method of Administration
IVEMEND should be administered intravenously and should not be given by the intramuscular or subcutaneous route. Intravenous administration occurs preferably through a running intravenous infusion over 15 minutes (see section 6.6). Do not administer IVEMEND as a bolus injection or undiluted solution.
4.3 Contraindications
Hypersensitivity to the active substance, aprepitant, or to polysorbate 80 or any of the other excipients.
Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).
4.4 Special Warnings And Precautions For Use
There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. IVEMEND should be used with caution inthese patients (see section 5.2).
IVEMEND and oral aprepitant should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such as ciclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, and quinidine (see section 4.5). Additionally, concomitant administration with irinotecan should be approached with particular caution as the combination might result in increased toxicity.
Co-administration of fosaprepitant with ergot alkaloid derivatives, which are CYP3A4 substrates, may result in elevated plasma concentrations of these active substances. Therefore, caution is advised due to the potential risk of ergot-related toxicity.
Co-administration of oral aprepitant with warfarin results in decreased prothrombin time, reported as International Normalised Ratio (INR). In patients on chronic warfarin therapy, the INR should be monitored closely during treatment with oral aprepitant and for 2 weeks following each 3-day regimen of fosaprepitant followed by oral aprepitant for chemotherapy induced nausea and vomiting (see section 4.5).
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of aprepitant. Alternative or back-up methods of contraception should be used during treatment with fosaprepitant or aprepitant and for 2 months following the last dose of aprepitant (see section 4.5).
Concomitant administration of fosaprepitant with active substances that strongly induce CYP3A4 activity (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination results in reductions of the plasma concentrations of aprepitant (see section 4.5). Concomitant administration of fosaprepitant with herbal preparations containing St. John's Wort (Hypericum perforatum) is not recommended.
Concomitant administration of fosaprepitant with active substances that inhibit CYP3A4 activity (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, and protease inhibitors) should be approached cautiously as the combination is expected to result in increased plasma concentrations of aprepitant (see section 4.5).
Isolated reports of immediate hypersensitivity reactions including flushing, erythema, and dyspnea have occurred during infusion of fosaprepitant. These hypersensitivity reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. It is not recommended to reinitiate the infusion in patients who experience hypersensitivity reactions.
IVEMEND should not be given as a bolus injection, but should always be diluted and given as a slow intravenous infusion (see section 4.2). IVEMEND should not be administered intramuscularly or subcutaneously. Mild injection site thrombosis has been observed at higher doses (see section 4.9). If signs or symptoms of local irritation occur, the injection or infusion should be terminated and restarted in another vein.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
When administered intravenously fosaprepitant is rapidly converted to aprepitant.
Drug interactions following administration of fosaprepitant are likely to occur with active substances that interact with oral aprepitant. The following information was derived from data with oral aprepitant and studies conducted with fosaprepitant and midazolam or diltiazem.
Aprepitant (125mg/80mg) is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. During treatment with oral aprepitant, CYP3A4 is inhibited. After the end of treatment, oral aprepitant causes a transient mild induction of CYP2C9, CYP3A4 and glucuronidation. Fosaprepitant or aprepitant does not seem to interact with the P-glycoprotein transporter, as demonstrated by the lack of interaction of oral aprepitant with digoxin.
Effect of aprepitant on the pharmacokinetics of active substances.
CYP3A4 inhibition
As a moderate inhibitor of CYP3A4, aprepitant can increase plasma concentrations of orally co-administered active substances that are metabolised through CYP3A4. The total exposure of orally administered CYP3A4 substrates may increase up to approximately 3-fold during the 3-day treatment with fosaprepitant followed by oral aprepitant; the effect of aprepitant on the plasma concentrations of intravenously administered CYP3A4 substrates is expected to be smaller. Fosaprepitant must not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these active substances, potentially causing serious or life-threatening reactions. (see section 4.3).Caution is advised during concomitant administration of fosaprepitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such as ciclosporin, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, and quinidine (see section 4.4).
Corticosteroids:
Dexamethasone: The usual oral dexamethasone dose should be reduced by approximately 50 % when co
Methylprednisolone: The usual intravenously administered methylprednisolone dose should be reduced approximately 25 %, and the usual oral methylprednisolone dose should be reduced approximately 50 % when co-administered with a regimen of fosaprepitant followed by aprepitant. Oral 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, a CYP3A4 substrate, by 1.3-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was co-administered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3.
During continuous treatment with methylprednisolone, the AUC of methylprednisolone may decrease at later time points within 2 weeks following initiation of dosing with oral aprepitant, due to the inducing effect of aprepitant on CYP3A4. This effect may be expected to be more pronounced for orally administered methylprednisolone.
Chemotherapeutic agents: In pharmacokinetic studies, oral aprepitant, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, did not influence the pharmacokinetics of docetaxel administered intravenously on Day 1 or vinorelbine administered intravenously on Day 1 or Day 8. Because the effect of aprepitant on the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of aprepitant on the pharmacokinetics of intravenously administered CYP3A4 substrates, an interaction with orally administered chemotherapeutic agents metabolised primarily or in part by CYP3A4 (e.g., etoposide, vinorelbine) cannot be excluded. Caution is advised and additional monitoring may be appropriate in patients receiving such agents (see section 4.4).
Immunosuppressants:
During the 3 day CINV regimen, a transient moderate increase followed by a mild decrease in exposure of immunosuppressants metabolised by CYP3A4 (e.g. ciclosporin, tacrolimus, everolimus and sirolimus) is expected. Given the short duration of the 3-day regimen and the time-dependent limited changes in exposure, dose reduction of the immunosuppressants is not recommended during the 3 days of co-administration with EMEND.
Midazolam: The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolised via CYP3A4 (alprazolam, triazolam) should be considered when co
Fosaprepitant given at a dose of 100 mg over 15 minutes with a single dose of midazolam 2 mg increased the AUC of midazolam 1.6-fold. This effect was not considered clinically important.
Oral aprepitant increased the AUC of midazolam 2.3-fold on Day 1 and 3.3-fold on Day 5, when a single oral dose of midazolam 2 mg was co-administered on Days 1 and 5 of a regimen of oral aprepitant 125 mg on Day 1 and 80 mg/day on Days 2 to 5.
In another study with intravenous administration of midazolam, oral aprepitant was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, and midazolam 2 mg was given intravenously prior to the administration of the 3-day regimen of oral aprepitant and on Days 4, 8, and 15. Oral aprepitant increased the AUC of midazolam 25 % on Day 4 and decreased the AUC of midazolam 19 % on Day 8 and 4 % on Day 15. These effects were not considered clinically important.
In a third study with intravenous and oral administration of midazolam, oral aprepitant was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, together with ondansetron 32 mg Day 1, dexamethasone, 12 mg Day 1 and 8 mg Days 2-4. This combination (i.e. oral aprepitant, ondansetron and dexamethasone)decreased the AUC of oral midazolam 16 % on Day 6, 9 % on Day 8, 7 % on Day 15 and 17 % on Day 22. These effects were not considered clinically important.
A fourth study was completed with intravenous administration of midazolam and oral aprepitant. Intravenous midazolam 2 mg was given 1 hour after oral administration of a single dose of oral aprepitant 125 mg. The plasma AUC of midazolam was increased by 1.5
Diltiazem: In patients with mild to moderate hypertension, infusion of 100 mg fosaprepitant over 15 minutes with diltiazem 120 mg 3 times daily, resulted in a 1.4-fold increase in diltiazem AUC and a small but clinically meaningful decrease in blood pressure, but did not result in a clinically meaningful change in heart rate, or PR interval.
Induction
As a mild inducer of CYP2C9, CYP3A4 and glucuronidation, aprepitant can decrease plasma concentrations of substrates eliminated by these routes within two weeks following initiation of dosing regimen. This effect may become apparent only after the end of a 3 day regimen of fosaprepitant followed by aprepitant. For CYP2C9 and CYP3A4 substrates, the induction is transient with a maximum effect reached 3-5 days after end of the oral aprepitant 3-day treatment. The effect is maintained for a few days, thereafter slowly declines and is clinically insignificant by two weeks after end of oral aprepitant treatment. Mild induction of glucuronidation is also seen with 80 mg oral aprepitant given for 7 days. Data are lacking regarding effects on CYP2C8 and CYP2C19. Caution is advised when warfarin, acenocoumarol, tolbutamide, phenytoin or other active substances that are known to be metabolised by CYP2C9 are administered during this time period.
Warfarin: In patients on chronic warfarin therapy, the prothrombin time (INR) should be monitored closely during treatment with fosaprepitant or aprepitant and for 2 weeks following each 3-day regimen for chemotherapy induced nausea and vomiting (see section 4.4). When a single 125 mg dose of oral aprepitant was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilised on chronic warfarin therapy, there was no effect of oral aprepitant on the plasma AUC of R(+) or S(-) warfarin determined on Day 3; however, there was a 34 % decrease in S(-) warfarin (a CYP2C9 substrate) trough concentration accompanied by a 14 % decrease in INR 5 days after completion of dosing with oral aprepitant.
Tolbutamide: Oral aprepitant, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 23 % on Day 4, 28 % on Day 8, and 15 % on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day regimen of oral aprepitant and on Days 4, 8, and 15.
Hormonal contraceptives: The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of oral aprepitant. Alternative or back-up methods of contraception should be used during treatment with fosaprepitant or oral aprepitant and for 2 months following the last dose of aprepitant.
In a clinical study, single doses of an oral contraceptive containing ethinyl estradiol and norethindrone were administered on Days 1 through 21 with oral aprepitant, given as a regimen of 125 mg on Day 8 and 80 mg/day on Days 9 and 10 with ondansetron 32 mg intravenously on Day 8 and oral dexamethasone given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. During days 9 through 21 in this study, there was as much as a 64 % decrease in ethinyl estradiol trough concentrations and as much as a 60 % decrease in norethindrone trough concentrations.
5-HT3 antagonists: In clinical 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 agents on the pharmacokinetics of aprepitant
Concomitant administration of fosaprepitant or aprepitant with active substances that inhibit CYP3A4 activity (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin nefazodone, and protease inhibitors) should be approached cautiously, as the combination is expected to result in increased plasma concentrations of aprepitant (see section 4.4).
Concomitant administration of fosaprepitant or aprepitant with active substances that strongly induce CYP3A4 activity (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy. Concomitant administration of fosaprepitant with herbal preparations containing St. John's Wort Hypericum perforatum) is not recommended.
Ketoconazole: When a single 125 mg dose of oral 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.
Diltiazem: Infusion of 100 mg fosaprepitant over 15 minutes with diltiazem 120 mg 3 times daily, resulted in a 1.5-fold increase of aprepitant AUC. This effect was not considered clinically important.
Rifampicin: When a single 375 mg dose of oral aprepitant was administered on Day 9 of a 14-day regimen of 600 mg/day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased 91 % and the mean terminal half-life decreased 68 %.
4.6 Pregnancy And Lactation
For fosaprepitant and aprepitant no clinical data on exposed pregnancies are available.
The potential for reproductive toxicities of fosaprepitant and aprepitant have not been fully characterized, since exposure levels above the therapeutic exposure in humans were not attained in animal studies. These studies did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The potential effects on reproduction of alterations in neurokinin regulation are unknown. IVEMEND should not be used during pregnancy unless clearly necessary.
Aprepitant is excreted in the milk of lactating rats after intravenous administration of fosaprepitant as well as after oral administration of aprepitant. It is not known whether aprepitant is excreted in human milk. Therefore, breast-feeding is not recommended during treatment with IVEMEND and oral aprepitant.
4.7 Effects On Ability To Drive And Use Machines
No studies on the effects of IVEMEND on the ability to drive and use machines have been performed. However, when driving vehicles or operating machines, it should be taken into account that dizziness and fatigue have been reported after using IVEMEND (see section 4.8).
4.8 Undesirable Effects
Since fosaprepitant is converted to aprepitant, those adverse reactions associated with aprepitant are expected to occur with fosaprepitant. The safety profile of fosaprepitant was evaluated in approximately 1100 individuals The safety profile of aprepitant was evaluated in approximately 6100 individuals. Various formulations of fosaprepitant have been administered to a total of 2183 individuals including 371 healthy subjects and 1579 patients with CINV.
Oral aprepitant
Adverse reactions considered as drug-related by the investigator were reported in approximately 17 % of patients treated with the aprepitant regimen compared with approximately 13 % of patients treated with standard therapy in patients receiving highly emetogenic chemotherapy (HEC). Aprepitant was discontinued due to adverse reactions in 0.6 % of patients treated with the aprepitant regimen compared with 0.4 % of patients treated with standard therapy. In a combined analysis of 2 clinical studies of patients receiving moderately emetogenic chemotherapy (MEC), clinical adverse reactions were reported in approximately 14 % of patients treated with the aprepitant regimen compared with approximately 15 % of patients treated with standard therapy. Aprepitant was discontinued due to adverse reactions in 0.7 % of patients treated with the aprepitant regimen compared with 0.2 % of patients treated with standard therapy.
The most common adverse reactions reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving highly emetogenic chemotherapy were: hiccups (4.6 % versus 2.9%), asthenia/fatigue (2.9 % versus 1.6%), alanine transferase (ALT) increased (2.8 % versus 1.5%), constipation (2.2 % versus 2.0% ), headache (2.2 % versus 1.8%), and anorexia (2.0 % versus 0.5%). The most common adverse reaction reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving moderately emetogenic chemotherapy was fatigue (1.4 % versus 0.9%).
The following adverse reactions were observed in either HEC or MEC studies in patients treated with the aprepitant regimen and at a greater incidence than with standard therapy:
Frequencies are defined as: very common (
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*Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were reported as adverse reactions only thereafter.
The adverse reactions profiles in the Multiple-Cycle extension of HEC and MEC studies for up to 6 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.
In an additional active-controlled clinical study in 1169 patients receiving aprepitant and highly emetogenic chemotherapy, the adverse reactions profile was generally similar to that seen in the other HEC studies with aprepitant.
Additional adverse reactions were observed in patients treated with aprepitant (40 mg) for postoperative nausea and vomiting and a greater incidence than with ondansetron: abdominal pain upper, bowel sounds abnormal, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, sensory disturbance, stomach discomfort, visual acuity reduced, wheezing.
In addition, two serious adverse reactions were reported in clinical studies in postoperative nausea and vomiting (PONV) in patients taking a higher dose of aprepitant: one case of constipation, and one case of sub
One case of Stevens-Johnson syndrome was reported as a serious adverse event in a patient receiving aprepitant with cancer chemotherapy.
One case of angioedema and urticaria was reported as a serious adverse event in a patient receiving aprepitant in a non-CINV/non-PONV study.
IVEMEND (fosaprepitant)
In an active-controlled clinical study in patients receiving highly emetogenic chemotherapy, safety was evaluated for 1143 patients receiving the 1-day regimen of fosaprepitant 150 mg compared to 1169 patients receiving the 3-day regimen of aprepitant. The safety profile was generally similar to that seen in the aprepitant table above.
The following are clinically important adverse reactions reported in patients receiving fosaprepitant that have not been reported with aprepitant as described above. Frequencies are defined as: very common (
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Post-marketing experience
During post-marketing experience, the following side effects have been reported (frequency not known):
Skin and subcutaneous tissue disorders: pruritus, rash, urticaria
Immune system disorders: hypersensitivity reactions including anaphylactic reactions
Immediate hypersensitivity reactions have been observed during the infusion of fosaprepitant which may include the following: flushing, erythema, dyspnea (see section 4.4).
4.9 Overdose
No specific information is available on the treatment of overdose.
Drowsiness and headache were reported in one patient who ingested 1,440 mg of aprepitant.
Single doses up to 200 mg of fosaprepitant were generally well tolerated in healthy subjects.
Three out of 33 subjects receiving 200 mg of fosaprepitant experienced mild injection site thrombosis.
In the event of overdose, fosaprepitant 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.
Aprepitant cannot be removed by haemodialysis.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04A D12
Fosaprepitant is the prodrug of aprepitant and when administered intravenously is converted rapidly to aprepitant (see section 5.2). The contribution of fosaprepitant to the overall antiemetic effect has not fully been characterized, but a transient contribution during the initial phase cannot be ruled out. Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors. The pharmacological effect of fosaprepitant is attributed to aprepitant.
In 2 randomised, double-blind studies encompassing a total of 1,094 patients receiving chemotherapy that included cisplatin 2, aprepitant in combination with an ondansetron/dexamethasone regimen (see section 4.2) was compared with a standard regimen (placebo plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on Day 1 and 8 mg orally twice daily on Days 2 to 4).
Efficacy was based on evaluation of the following composite measure: complete response (defined as no emetic episodes and no use of rescue therapy) primarily during Cycle 1. The results were evaluated for each individual study and for the 2 studies combined.
A summary of the key study results from the combined analysis is shown in Table 1.
Table 1
Percent of Patients Receiving Highly Emetogenic Chemotherapy Responding by Treatment Group and Phase — Cycle 1
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* The confidence intervals were calculated with no adjustment for gender and concomitant chemotherapy, which were included in the primary analysis of odds ratios and logistic models.
† One patient in the Aprepitant Regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses; one patient in the Standard Regimen only had data in the delayed phase and was excluded from the overall and acute phase analyses.
The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in Figure 1.
Figure 1
Percent of Patients Receiving Highly Emetogenic Chemotherapy Who Remain Emesis Free Over Time – Cycle 1
Statistically significant differences in efficacy were also observed in each of the 2 individual studies.
In the same 2 clinical studies, 851 patients continued into the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy. The efficacy
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