Several things patients must know when taking the drug: What are the warnings and precautions for ixazomib?

In clinical studies of ixazomib, warnings and precautions such as thrombocytopenia, gastrointestinal toxicity, peripheral neuropathy, peripheral edema, skin reactions, thrombotic microangiopathy, hepatotoxicity, and embryo-fetal toxicity have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Thrombocytopenia: The lowest value of platelets in the study usually occurs on days 14-21 of each 28-day cycle and returns to baseline at the beginning of the next cycle. Monitor platelet counts at least monthly during treatment with ixazomib. Consider more frequent monitoring during the first three cycles. Control thrombocytopenia with dose adjustments and platelet transfusions according to standard medical guidelines.

2. Gastrointestinal toxicity: Diarrhea, constipation, nausea and vomiting may occur, occasionally requiring the use of antidiarrheal and antiemetics and supportive care.

3. Peripheral neuropathy: The most commonly reported reaction is peripheral sensory neuropathy. Peripheral motor neuropathy is uncommon in either regimen. Four percent of patients in the ixazomib regimen discontinued one or more of the three drugs due to peripheral neuropathy. Patients should be monitored for symptoms of neuropathy. Dosage adjustments may be required in patients who develop new or worsening peripheral neuropathy.

4. Peripheral edema: According to reports, grade 3 peripheral edema occurred in 2% of patients in the ixazomib regimen. In both regimens, peripheral edema resulted in discontinuation of one or more of the three drugs in less than 1% of patients. Assess potential causes and provide supportive care if necessary.

5. Skin reaction: The most common types of rash include maculopapular rash and macular rash. In both regimens, rash led to discontinuation of one or more of the three drugs in less than 1% of patients. Control rash with supportive care or dose adjustment (Grade 2 or higher). Stevens-Johnson syndrome has also been reported, including one death. If Stevens-Johnson syndrome occurs, discontinue ixazomib and manage as clinically indicated. Consider antiviral prophylaxis in patients receiving treatment to reduce the risk of recurrence of herpes zoster.

6. Thrombotic microangiopathy: Including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Monitor for signs and symptoms of TTP/HUS disease. If the diagnosis is in doubt, discontinueuseixazomib and obtain an evaluation. If the diagnosis of TTP/HUS is ruled out, consider restarting ixazomib. The safety of restarting ixazomib therapy in patients with preexisting TTP/HUS is unknown.

7. Liver poisoning: The incidence of drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestasis, and hepatotoxicity has been reported to be less than 1% in patients treated with ixazomib. Hepatotoxicity has been reported (10% in the ixazomib regimen). Monitor liver enzymes regularly and adjust dose for Grade 3 or 4 symptoms.

8. Embryonic-Fetal Toxicity: Based on mechanism of action and animal studies, ixazomib has been found to cause fetal harm when administered to pregnant rats and in pregnant rats and rabbits, resulting in exposures slightly higher than those observed in patients receiving recommended doses. Inform pregnant women of potential risks to the fetus. Advise women of childbearing potential to use an effective non-hormonal method of contraception during treatment with the drug and for 90 days after the last dose. It is recommended that men with female partners use effective contraception during treatment and for 90 days after the last dose.