NINLARO Hard capsule Ref.[9136] Active ingredients: Ixazomib

Treatment must be initiated and monitored under the supervision of a physician experienced in the management of multiple myeloma.

Posology

The recommended starting dose of ixazomib 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.

Dosing schedule. Ixazomib taken with lenalidomide and dexamethasone:

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 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 section 5.1).

Delayed or missed doses

In the event that a ixazomib 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 dose reduction steps are presented in Table 1 and the dose modification guidelines are provided in Table 2.

Table 1. Ixazomib dose reduction steps:

* Recommended reduced dose of 3 mg in the presence of moderate or severe hepatic impairment, severe renal impairment or end-stage renal disease (ESRD) requiring dialysis.

An alternating dose modification approach is recommended for ixazomib 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, section 4.2 for the dose reduction steps for these toxicities.

Table 2. Dose modifications guidelines for ixazomib in combination with lenalidomide and dexamethasone:

Concomitant medicinal products

Antiviral prophylaxis should be considered in patients being treated with ixazomib to decrease the risk of herpes zoster reactivation. Patients included in studies with ixazomib 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 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 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 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 regimen and 9 patients (15%) in the placebo regimen.

Hepatic impairment

No dose adjustment of ixazomib 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 section 5.2).

Renal impairment

No dose adjustment of ixazomib 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 is not dialyzable and, therefore, can be administered without regard to the timing of dialysis (see section 5.2).

Refer to the lenalidomide SmPC for dosing recommendations in patients with renal impairment.

Paediatric population

The safety and efficacy of ixazomib in children below 18 years of age have not been established. No data are available.

Method of administration

Ixazomib is for oral use.

Ixazomib 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 section 5.2). The capsule should be swallowed whole with water. It should not be crushed, chewed, or opened (see section 6.6).

There is no known specific antidote for ixazomib overdose. Clinical data is limited but doses up to 12 mg have been reported in the randomised controlled trial. In the event of an overdose, monitor the patient for adverse reactions (section 4.8) and provide appropriate supportive care.

Shelf life: 3 years.

Do not store above 30°C. Do not freeze.

Store in the original package in order to protect from moisture.

PVC-Aluminium/Aluminium blister sealed inside a wallet pack containing one capsule.

Three single blister wallet packs are packaged in one carton.