Ninlaro Special Precautions

As IXAZOMIB (NINLARO) is administered in combination with lenalidomide and dexamethasone, refer to the SmPC for these medicinal products for additional special warnings and precautions for use.
Thrombocytopenia: Thrombocytopenia has been reported with IXAZOMIB (NINLARO) (see Adverse Reactions) with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle (see Adverse Reactions).
Platelet counts should be monitored at least monthly during IXAZOMIB (NINLARO) treatment.
More frequent monitoring should be considered during the first three cycles as per the lenalidomide SmPC. Thrombocytopenia can be managed with dose modifications (see Dosage & Administration) and platelet transfusions as per standard medical guidelines.
Gastrointestinal toxicities: Diarrhoea, constipation, nausea and vomiting have been reported with IXAZOMIB (NINLARO), occasionally requiring use of antiemetic and antidiarrhoeal medicinal products and supportive care (see Adverse Reactions). The dose should be adjusted for severe (Grade 3-4) symptoms (see Dosage & Administration). In case of severe gastrointestinal events, monitoring of serum potassium level is recommended.
Peripheral neuropathy: Peripheral neuropathy has been reported with IXAZOMIB (NINLARO) (see Adverse Reactions). The patient should be monitored for symptoms of peripheral neuropathy. Patients experiencing new or worsening peripheral neuropathy may require dose modification (see Dosage & Administration).
Peripheral oedema: Peripheral oedema has been reported with IXAZOMIB (NINLARO) (see Adverse Reactions). The patient should be evaluated for underlying causes and provide supportive care, as necessary. The dose of dexamethasone should be adjusted per its prescribing information or IXAZOMIB (NINLARO) for Grade 3 or 4 symptoms (see Dosage & Administration).
Cutaneous reactions: Rash has been reported with IXAZOMIB (NINLARO) (see Adverse Reactions). Rash should be managed with supportive care or with dose modification if Grade 2 or higher (see Dosage & Administration). Stevens-Johnson syndrome has also been reported with ixazomib (see Adverse Reactions). If Stevens-Johnson syndrome occurs, discontinue ixazomib.
Thrombotic microangiopathy: Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP), have been reported in patients who received ixazomib. Some of these events have been fatal. Signs and symptoms of TMA should be monitored for. If the diagnosis is suspected, stop ixazomib and evaluate patients for possible TMA. If the diagnosis of TMA is excluded, ixazomib can be restarted. The safety of reinitiating ixazomib therapy in patients previously experiencing TMA is not known.
Hepatotoxicity: Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have been uncommonly reported with IXAZOMIB (NINLARO) (see Adverse Reactions).
Hepatic enzymes should be monitored regularly and the dose should be adjusted for Grade 3 or 4 symptoms (see Dosage & Administration).
Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has occurred in patients receiving IXAZOMIB (NINLARO). PRES is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, altered consciousness, and visual disturbances. Brain imaging, preferably Magnetic Resonance Imaging, is used to confirm the diagnosis. In patients developing PRES, discontinue IXAZOMIB (NINLARO).
Strong CYP3A inducers: Strong inducers may reduce the efficacy of IXAZOMIB (NINLARO), therefore the concomitant use of strong CYP3A inducers such as carbamazepine, phenytoin, rifampicin and St. John's Wort (Hypericum perforatum), should be avoided (see Interactions and Pharmacology: Pharmacokinetics under Actions). Closely monitor patients for disease control if co-administration with a strong CYP3A inducer cannot be avoided.
Effects on ability to drive and use machines: IXAZOMIB (NINLARO) has minor influence on the ability to drive or use machines. Fatigue and dizziness have been observed in clinical trials. Patients should be advised not to drive or operate machines if they experience any of these symptoms.
Use in Pregnancy: Women should avoid becoming pregnant while being treated with IXAZOMIB (NINLARO). If IXAZOMIB (NINLARO) is used during pregnancy or if the patient becomes pregnant while taking IXAZOMIB (NINLARO), the patient should be apprised of the potential hazard to the foetus. Women of childbearing potential must use highly effective contraception while taking IXAZOMIB (NINLARO) and for 90 days after stopping treatment (see Interactions and Use in Pregnancy & Lactation).
Women using hormonal contraceptives should additionally use a barrier method of contraception.