Ninlaro Dosage/Direction for Use

Treatment must be initiated and monitored under the supervision of a physician experienced in the management of multiple myeloma.
In combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy: The recommended starting dose of IXAZOMIB (NINLARO) is 4 mg administered orally once a week on Days 1, 8, and 15 of a 28-day treatment cycle.
The recommended starting dose of lenalidomide is 25 mg administered daily on Days 1 to 21 of a 28-day treatment cycle.
The recommended starting dose of dexamethasone is 40 mg administered on Days 1, 8, 15, and 22 of a 28-day treatment cycle. (See Table 4.)

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For additional information regarding lenalidomide and dexamethasone, refer to the Summary of Product Characteristics (SmPC) for these medicinal products.
Prior to initiating a new cycle of therapy: Absolute neutrophil count should be ≥ 1,000/mm³; Platelet count should be ≥ 75,000/mm³; Non haematologic toxicities should, at the physician's discretion, generally be recovered to patient's baseline condition or ≤ Grade 1 Treatment should be continued until disease progression or unacceptable toxicity. Treatment with IXAZOMIB (NINLARO) in combination with lenalidomide and dexamethasone for longer than 24 cycles should be based on an individual benefit risk assessment, as the data on the tolerability and toxicity beyond 24 cycles are limited (see Pharmacology: Pharmacodynamics under Actions).
Delayed or missed doses: In the event that a IXAZOMIB (NINLARO) dose is delayed or missed, the dose should be taken only if the next scheduled dose is ≥ 72 hours away. A missed dose should not be taken within 72 hours of the next scheduled dose. A double dose should not be taken to make up for a missed dose.
If a patient vomits after taking a dose, the patient should not repeat the dose but should resume dosing at the time of the next scheduled dose.
Dose modifications: The IXAZOMIB (NINLARO) dose reduction steps are presented in Table 5 and the dose modification guidelines are provided in Table 6. (See Table 5.)

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An alternating dose modification approach is recommended for IXAZOMIB (NINLARO) and lenalidomide for overlapping toxicities of thrombocytopenia, neutropenia and rash. For these toxicities, the first dose modification step is to withhold/reduce lenalidomide. Refer to the lenalidomide SmPC, under Dosage & Administration for the dose reduction steps for these toxicities. (See Table 6.)

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Maintenance therapy with multiple myeloma following autologous stem cell transplant and for those who had not been treated with stem cell transplantation: This drug is administered orally to adult patients usually in a fasted state, once a week for three weeks (Days 1, 8, and 15), followed by 13 days rest period (Days 16 - 28). This four-week treatment cycle is repeated. For cycle 1 - 4, the dose is 3 mg. For cycle 5 or later, the dose is 4 mg. The dosage may be reduced depending on the condition of the individual patient.
The efficacy and safety of this drug given in combination with other antineoplastic drugs other than lenalidomide and dexamethasone have not been established.
The efficacy and safety of this drug as dosing more than 24 months have not been established.
When an adverse reaction occurs with this drug, administration of this drug should be withheld, reduced, or discontinued referring to the following criteria.
Dose Reduction Steps for this Drug: (see Table 7).

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Criteria for Withholding, Dose Reduction, or Discontinuation: (see Table 8).

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Concomitant medicinal products: Antiviral prophylaxis should be considered in patients being treated with IXAZOMIB (NINLARO) to decrease the risk of herpes zoster reactivation. Patients included in studies with IXAZOMIB (NINLARO) who received antiviral prophylaxis had a lower incidence of herpes zoster infection compared to patients who did not receive prophylaxis.
Thromboprophylaxis is recommended in patients being treated with IXAZOMIB (NINLARO) in combination with lenalidomide and dexamethasone and should be based on an assessment of the patient's underlying risks and clinical status.
For other concomitant medicinal products that may be required, refer to the current lenalidomide and dexamethasone SmPC.
Special patient populations: Elderly: No dose adjustment of IXAZOMIB (NINLARO) is required for patients over 65 years of age. Discontinuations in patients > 75 years of age were reported in 13 patients (28%) in the IXAZOMIB (NINLARO) regimen and 10 patients (16%) in the placebo regimen. Cardiac arrhythmias in patients > 75 years of age were observed in 10 patients (21%) in the IXAZOMIB (NINLARO) regimen and 9 patients (15%) in the placebo regimen.
Hepatic impairment: No dose adjustment of IXAZOMIB (NINLARO) is required for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin > 1-1.5 x ULN and any AST). The reduced dose of 3 mg is recommended in patients with moderate (total bilirubin > 1.5-3 x ULN) or severe (total bilirubin > 3 x ULN) hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Renal impairment: No dose adjustment of IXAZOMIB (NINLARO) is required for patients with mild or moderate renal impairment (creatinine clearance ≥ 30 mL/min). The reduced dose of 3 mg is recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease (ESRD) requiring dialysis. IXAZOMIB (NINLARO) is not dialyzable and, therefore, can be administered without regard to the timing of dialysis (see Pharmacology: Pharmacokinetics under Actions). Refer to the lenalidomide SmPC for dosing recommendations in patients with renal impairment.
Paediatric population: The safety and efficacy of IXAZOMIB (NINLARO) in children below 18 years of age have not been established. No data are available.
Method of administration: IXAZOMIB (NINLARO) is for oral use.
IXAZOMIB (NINLARO) should be taken at approximately the same time on days 1, 8, and 15 of each treatment cycle at least 1 hour before or at least 2 hours after food (see Pharmacology: Pharmacokinetics under Actions).
The capsule should be swallowed whole with water. It should not be crushed, chewed, or opened (see Special precautions for disposal and other handling under Cautions for Usage).