akynzeo

Recommended Dosage AKYNZEO capsules: The recommended dosage is one AKYNZEO capsule administered 1 hour prior to the start of chemotherapy, with or without food. ( 2.1 ) Preparation and Administration AKYNZEO injection is supplied either as a Ready-to-Use (with hanger) vial or a To-be-Diluted vial. (2.2) AKYNZEO for injection requires dilution prior to administration. ( 2.3 ) See full prescribing information for information on preparation, administration, and incompatibilities for each product. (2.2, 2.3, 2.4 ) 2.1 Recommended Dosage The recommended dosages of AKYNZEO and dexamethasone in adults for the prevention of nausea and vomiting associated with administration of emetogenic chemotherapy are shown in Table 1. AKYNZEO capsules can be taken with or without food. Table 1: Antiemetic Treatment Regimen Treatment Regimen Day 1 Days 2 to 4 Highly Emetogenic Chemotherapy, including Cisplatin-Based Chemotherapy AKYNZEO capsules 1 capsule of AKYNZEO 1 hour before chemotherapy Dexamethasone 8 mg once a day Dexamethasone 12 mg 30 minutes before chemotherapy AKYNZEO for injection and AKYNZEO injection 1 vial of AKYNZEO Infuse over 30 minutes starting 30 minutes before chemotherapy [see Dosage and Administration (2.2)] Dexamethasone 8 mg once a day Dexamethasone 12 mg 30 minutes before chemotherapy Anthracyclines and Cyclophosphamide-Based Chemotherapy and Chemotherapy Not Considered…

The following clinically significant adverse reactions are found elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (≥3%) for AKYNZEO capsules are headache, asthenia, dyspepsia, fatigue, constipation and erythema ( 6.1 ) The safety profile of AKYNZEO for injection was generally similar to that seen with AKYNZEO capsules. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact HELSINN at 1-844-357-4668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 practice. AKYNZEO Capsules The overall safety of AKYNZEO capsules was evaluated in 1538 cancer patients and healthy subjects in clinical trials. The data described below reflect exposure to AKYNZEO in 1169 cancer patients, receiving at least one cycle of cancer chemotherapy in 3 active-controlled trials [see Clinical Studies ( 14 .1 )] , including 782 exposed to AKYNZEO for at least 4 cycles and 321 exposed for at least 6 cycles, up to a maximum of 12 cycles of chemotherapy. The median age was 55, 79% were female, 83% were…

None. None ( 4 )

In the event of overdose, AKYNZEO should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of AKYNZEO, drug- induced emesis may not be effective. Dialysis studies have not been performed; due to the large volume of distribution, dialysis is unlikely to be an effective treatment for AKYNZEO overdose. A total of 33 adult cancer patients were administered oral palonosetron at a dose of 90 mcg/kg (approximately 12 times the recommended dose in AKYNZEO capsules), as part of a dose ranging study and had a similar incidence of adverse reactions compared to lower doses. A single dose of 600 mg (2 times the recommended dose in AKYNZEO capsules) of oral netupitant was administered to 49 healthy subjects and a similar incidence of adverse reactions was observed when compared to lower doses of netupitant in cancer patients and healthy subjects.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

CYP3A4 Substrates: inhibition of CYP3A4 by netupitant can result in increased plasma concentrations of the concomitant drug for 6 days after single dosage administration of AKYNZEO; avoid concomitant CYP3A4 substrates for one week, if feasible. If not avoidable, consider dose reduction of the CYP3A4 substrate ( 7.1 ) CYP3A4 Inducers (e.g., rifampin): decreased plasma concentrations of netupitant; avoid use ( 7.2 ) 7.1 Effects of AKYNZEO on Other Drugs Interaction with CYP3A4 Substrates Netupitant is a moderate inhibitor of CYP3A4. AKYNZEO should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. A single oral dose of netupitant 300 mg significantly inhibits CYP3A4 for 6 days. Avoid concomitant use of drugs that are CYP3A4 substrates for one week, if feasible. If not avoidable, consider dose reduction of CYP3A4 substrates. Dexamethasone A single oral dose of netupitant 300 mg or a single fosnetupitant infusion of 235 mg increased the systemic exposure of concomitant dexamethasone more than 2-fold on Days 2 and 4. Administer a reduced dose of dexamethasone with AKYNZEO [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.3 )] . Midazolam When administered with netupitant, the systemic exposure to midazolam was significantly increased. Consider the potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) when administering these drugs with AKYNZEO [see Clinical Pharmacology ( 12.3 )] . Chemotherapeutic Agents The systemic exposure of chemotherapy agents metabolized by CYP3A4 can increase when administered with AKYNZEO. Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, cyclophosphamide, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine [see Clinical Pharmacology ( 12.3 )] . Caution and monitoring for chemotherapeutic related adverse reactions are advised in patients receiving chemotherapy agents metabolized primarily by CYP3A4. Oral Contraceptives There is no clinically significant effect of AKYNZEO on the efficacy of oral contraceptives containing levonorgestrel and ethinyl estradiol [see Clinical Pharmacology ( 12.3 )] . Warfarin Although it was predicted that co-administration of intravenous AKYNZEO with warfarin would not substantially increase the systemic exposure to S-warfarin (CYP2C9 substrate), the active enantiomer, the effects of AKYNZEO for injection and AKYNZEO capsules on INR and prothrombin time have not been studied. Monitor INR and adjust the dosage of warfarin, as needed with concomitant use of AKYNZEO, to maintain the target INR range. 7.2 Effects of Other Drugs on AKYNZEO Netupitant is mainly metabolized by CYP3A4. Palonosetron is mainly metabolized by CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2. CYP3A4 Inducers Avoid concomitant use of AKYNZEO in patients who are chronically using a strong CYP3A4 inducer such as rifampin. A strong CYP3A inducer can decrease the efficacy of AKYNZEO by substantially reducing plasma concentrations of the netupitant component [see Clinical Pharmacology ( 12.3 )] . CYP3A4 Inhibitors Concomitant use of AKYNZEO with a strong CYP3A4 inhibitor (e.g., ketoconazole) can increase the systemic exposure to the netupitant component of AKYNZEO. However, no dosage adjustment is necessary for single dose administration of AKYNZEO [see Clinical Pharmacology ( 12.3 )] . 7.3 Serotonergic Drugs Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). If symptoms occur, discontinue AKYNZEO and initiate supportive treatment [see Warnings and Precautions ( 5.2 )].