openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS CYP2D6 Substrates : Rolapitant is a moderate inhibitor of CYP2D6 and significantly increases the plasma concentrations of CYP2D6 substrates for at least 28 days following single dose administration of VARUBI. Before starting VARUBI, consider if patients require: thioridazine or pimozide; if so, use an alternative antiemetic to VARUBI or an alternative to thioridazine or pimozide that is not metabolized by CYP2D6. other CYP2D6 substrates; if so, consult the prescribing information for the CYP2D6 substrate for additional information about interactions with CYP2D6 inhibitors. ( 4 , 5.1 , 7 ) 5.1 Interaction with CYP2D6 Substrates Rolapitant is a moderate inhibitor of CYP2D6. Exposure to dextromethorphan, a CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in dextromethorphan (CYP2D6 substrate) concentrations, the last time point measured. The inhibitory effect of rolapitant on CYP2D6 is expected to persist beyond 28 days for an unknown duration following administration of VARUBI [see Drug Interactions (7) , Clinical Pharmacology (12.3) ] . Narrow Therapeutic Index Drugs (Thioridazine and Pimozide) VARUBI is contraindicated in patients taking CYP2D6 substrates with a narrow therapeutic index such as thioridazine and pimozide. Increased plasma concentrations of thioridazine and pimozide are associated with serious and/or life-threatening events of QT prolongation and Torsades de Pointes [see Contraindications (4) ] . Before starting treatment with VARUBI, consider whether patients require treatment with thioridazine or pimozide. If patients require these drugs, use an alternative antiemetic to VARUBI or an alternative to thioridazine or pimozide that is not metabolized by CYP2D6. Other Drugs VARUBI can also increase plasma concentrations of other CYP2D6 substrates for at least 28 days following administration of VARUBI and may result in adverse reactions. Before starting treatment with VARUBI, consult the prescribing information for CYP2D6 substrates to obtain additional information about interactions with CYP2D6 inhibitors.
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Interaction with CYP2D6 Substrates [see Contraindications (4) , Warnings and Precautions (5.1) ] Most common adverse reactions (≥3%) are: Cisplatin Based Highly Emetogenic Chemotherapy: neutropenia, hiccups and abdominal pain. ( 6.1 ) Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide: decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TerSera Therapeutics at 1-844-334-4035 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 clinical practice. In 4 controlled clinical trials in patients receiving emetogenic cancer chemotherapy, VARUBI was given in combination with a 5-HT 3 receptor antagonist and dexamethasone. On Day 1 of Cycle 1 of chemotherapy, 1567 patients were treated with VARUBI and 1198 of these patients continued into the optional multiple cycle extension for up to 6 cycles of chemotherapy. The median number of cycles administered 180 mg of VARUBI was four. VARUBI 180 mg was administered to 1294 patients. In Cycle 1 adverse reactions were reported in approximately 7% of patients treated with VARUBI compared with approximately 6% of patients treated with control therapy. The most common adverse reactions reported with an incidence of ≥3% and greater than control are listed in Table 2 and Table 3 . Table 2: Most Common Adverse Reactions in Patients Receiving Cisplatin-Based Highly Emetogenic Chemotherapy (Cycle 1)* * all reactions occurring at ≥3% in the VARUBI group and for which the rate for VARUBI exceeds the rate for control VARUBI Regimen (VARUBI, Dexamethasone, and 5-HT 3 Receptor Antagonist) N = 624 Control (Placebo, Dexamethasone, and 5-HT 3 Receptor Antagonist) N = 627 Neutropenia 9% 8% Hiccups 5% 4% Abdominal Pain 3% 2% Table 3: Most Common Adverse Reactions in Patients Receiving Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide (Cycle 1)* *all reactions occurring at ≥3% in the VARUBI group and for which the rate for VARUBI exceeds the rate for control. VARUBI Regimen (VARUBI, Dexamethasone, and 5-HT 3 Receptor Antagonist) N = 670 Control (Placebo, Dexamethasone, and 5-HT 3 Receptor Antagonist) N = 674 Decreased appetite 9% 7% Neutropenia 7% 6% Dizziness 6% 4% Dyspepsia 4% 2% Urinary tract infection 4% 3% Stomatitis 4% 2% Anemia 3% 2% Adverse reactions in the multiple-cycle extensions of highly and moderately emetogenic chemotherapy studies for up to 6 cycles of chemotherapy were generally similar to that observed in Cycle 1.
adverse reactions table
<table ID="t2" width="100%" styleCode="Noautorules"><caption>Table 2: Most Common Adverse Reactions in Patients Receiving Cisplatin-Based Highly Emetogenic Chemotherapy (Cycle 1)* </caption><col width="19.200%" align="left"/><col width="39.467%" align="left"/><col width="41.333%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">* all reactions occurring at ≥3% in the VARUBI group and for which the rate for VARUBI exceeds the rate for control </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Toprule Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">VARUBI Regimen</content> <content styleCode="bold">(VARUBI, Dexamethasone, and 5-HT</content><content styleCode="bold"><sub>3 </sub></content><content styleCode="bold">Receptor Antagonist)</content> <content styleCode="bold">N = 624</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Control</content> <content styleCode="bold">(Placebo, Dexamethasone, and 5-HT</content><content styleCode="bold"><sub>3 </sub></content><content styleCode="bold">Receptor Antagonist)</content> <content styleCode="bold">N = 627</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Neutropenia </td><td align="center" valign="top" styleCode="Botrule Rrule">9% </td><td align="center" valign="top" styleCode="Botrule Rrule">8% </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Hiccups </td><td align="center" valign="top" styleCode="Botrule Rrule">5% </td><td align="center" valign="top" styleCode="Botrule Rrule">4% </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Abdominal Pain </td><td align="center" valign="top" styleCode="Botrule Rrule">3% </td><td align="center" valign="top" styleCode="Botrule Rrule">2% </td></tr></tbody></table>