Apretero 125mg/80mg Capsule

Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist. Aprepitant capsules are indicated - in combination with other antiemetic agents, in patients 12 years of age and older for prevention of: o acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin o nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) - for prevention of postoperative nausea and vomiting (PONV) in adults Limitations of Use: - Aprepitant has not been studied for treatment of established nausea and vomiting. - Chronic continuous administration of Aprepitant is not recommended.

---

Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

• CYP3A4 Interactions: Aprepitant is a substrate, weak-to-moderate inhibitor and inducer of CYP3A4; See Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustments of Aprepitant and concomitant drugs. - Warfarin (a CYP2C9 substrate): Risk of decreased INR of prothrombin time; monitor INR in 2-week period, particularly at 7 to 10 days, following initiation of Aprepitant. - Hormonal Contraceptives: Efficacy of contraceptives may be reduced during administration of and for 28 days following the last dose of Aprepitant. Use effective alternative or back-up methods of contraception. Clinically Significant CYP3A4 Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Use of Aprepitant with other drugs that are CYP3A4 substrates, may result in increased plasma concentration of the concomitant drug. Use of pimozide with Aprepitant is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide. Use of Aprepitant with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma conentrations of Aprepitant and result in an increased risk of adverse reactions related to Aprepitant. Use of Aprepitant with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in Aprepitant plasma concentrations and decreased efficacy of Aprepitant. See table 10 and 11 for a listing of potentially significant drug interactions. Decrease in INR with Concomitant Warfarin Coadministration of Aprepitant with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in International Normalized Ratio (INR) of prothrombin time. 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. Risk of Reduced Efficacy of Hormonal Contraceptives 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. Advise patients to use effective alternative or back-up methods of contraception during treatment with Aprepitant and for 1 month following the last dose of Aprepitant.

---

Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

Most common adverse reactions (≥3%) are: Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) - Adults: fatigue, diarrhea, asthenia, dyspepsia, abdominal pain, hiccups, white blood cell count decreased, dehydration, and alanine aminotransferase increased. - Pediatrics: neutropenia, headache, diarrhea, decreased appetite, cough, fatigue, hemoglobin decreased, dizziness, and hiccups. PONV - Adults: constipation and hypotension. Clinical Trials Experience 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. In 2 active-controlled clinical trials in patients receiving moderately emetogenic chemotherapy (MEC) (Studies 3 and 4), Aprepitant in combination with ondasetron and dexamethasone (Aprepitant regimen) was compared to ondansetron and dexamethasone alone (standard therapy). 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 1,412 patients treated with the Aprepitant regimen during Cycle 1 of chemotherapy and 1,099 of these patients continued into the Mutliplwe-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. Table 5: Most Common Adverse Reactions in Patients Receiving HEC and MEC from a Pooled Analysis of HEC and MEC Studies* Aprepitant, ondansetron, and dexamethasone † (N=1,412) Ondansetron and dexamethasone ‡ (N=1,396) 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 with the Aprepitant regimen are listed in Table 6. Abridged from the full prescribing information.

---

Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.