This section is intended for UK healthcare professionals. If you are a member of the public click here. If you have been prescribed Ninlaro click here.

Prescribing NINLARO

Oral NINLARO is a novel approach to proteasome inhibition, designed to deliver sustained efficacy in RRMM1,2

NINLARO is the first and only oral PI licensed in combination with Rd for the treatment of adult patients with MM who have received at least 1 prior therapy1

NINLARO + Rd significantly extends PFS vs Rd alone and offers a manageable side effect profile with the convenience of an all-oral regimen1,2

NINLARO ordering process for UK Healthcare Professionals

NINLARO is available in 3 strengths:

Name Strength Pack Size EAN Code PIP Code
Ninlaro (ixazomib) 4 mg 3 capsules 5035382000022 404-0960
Ninlaro (ixazomib) 3 mg 3 capsules 5035382000015 404-0952
Ninlaro (ixazomib) 2.3 mg 3 capsules 5035382000008 404-0945

Takeda is partnering with SpringMed Solutions to distribute NINLARO in the UK.
Customer Services and Lead Times:

SpringMed Solutions 4 Petre Road, Clayton Business Park, Clayton Le Moors, Accrington, Lancashire, BB5 5JB Email: orders@springmedsolutions.com Tel: 08455 240047 Fax: 01254 238605

  • Orders received by SpringMed on Monday to Thursday by 15:30 for delivery to the UK mainland will be shipped the same day and delivered the next day.*
  • Orders received on Friday before 15:30 will be processed that day and delivered on Monday. If the Monday is a bank holiday then the order will be shipped on Tuesday and delivered by Wednesday at the latest.

*There are certain geographical locations where there will be a 48 hour delivery lead time. These will be notified upon receipt of the order.

Before prescribing NINLARO

Therapeutic indication1

  • NINLARO (ixazomib capsules) in combination with lenalidomide and dexamethasone (Rd) is indicated for the treatment of adult patients with MM who have received at least one prior therapy

Contraindications1

  • Hypersensitivity to the active substance or to any of the excipients listed below:

NINLARO 4 mg capsule

NINLARO 4mg capsule
  • Microcrystalline cellulose
  • Magnesium stearate
  • Talc
  • Gelatin
  • Titanium dioxide (E171)
  • Yellow iron oxide (E172)
  • Red iron oxide (E172)
  • Shellac
  • Propylene glycol
  • Potassium hydroxide
  • Black iron oxide (E172)

NINLARO 3 mg capsule

NINLARO 3mg capsule
  • Microcrystalline cellulose
  • Magnesium stearate
  • Talc
  • Gelatin
  • Titanium dioxide (E171)
  • Black iron oxide (E172)
  • Shellac
  • Propylene glycol
  • Potassium hydroxide

NINLARO 2.3 mg capsule

NINLARO 2.3mg capsule
  • Microcrystalline cellulose
  • Magnesium stearate
  • Talc
  • Gelatin
  • Titanium dioxide (E171)
  • Red iron oxide (E172)
  • Shellac
  • Propylene glycol
  • Potassium hydroxide
  • Black iron oxide (E172)
  • As NINLARO is administered in combination with lenalidomide and dexamethasone, refer to the SmPC for these medicinal products for additional contraindications

Special warnings and precautions for use1

Thrombocytopenia

Thrombocytopenia has been reported with NINLARO, with platelet nadirs typically occurring between days 14 and 21 of each 28‑day cycle and recovery to baseline by the start of the next cycle (click here for guidance)

Gastrointestinal toxicities

Diarrhoea, constipation, nausea and vomiting have been reported with NINLARO, occasionally requiring use of antiemetic and antidiarrhoeal medicinal products and supportive care (click here for guidance)

Peripheral neuropathy

Peripheral neuropathy has been reported with NINLARO. Patient should be monitored for symptoms of peripheral neuropathy. Patients experiencing new or worsening peripheral neuropathy may require dose modification (click here for guidance)

Peripheral oedema

Peripheral oedema has been reported with NINLARO. 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 NINLARO for Grade 3 or 4 symptoms ( click here for guidance)

Cutaneous reactions/rash

Rash has been reported with NINLARO. Rash should be managed with supportive care or with dose modification (click here for guidance)

Hepatotoxicity

Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have been uncommonly reported with NINLARO. Hepatic enzymes should be monitored regularly and the dose should be adjusted for Grade 3 or 4 symptoms (click here for guidance)

Pregnancy

Women should avoid becoming pregnant while being treated with NINLARO. Male and female patients who are able to have children must use effective contraceptive measures while taking NINLARO and for 90 days after stopping treatment. Women using hormonal contraceptives should additionally use a barrier method of contraception

Posterior Reversible Encephalopathy Syndrome (PRES)

PRES has occurred in patients receiving 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 NINLARO

Strong CYP3A inducers

Strong inducers may reduce the efficacy of NINLARO, therefore the concomitant use of strong CYP3A inducers such as carbamazepine, phenytoin, rifampicin and St. John's Wort (hypericum perforatum) should be avoided. Closely monitor patients for disease control if co-administration with a strong CYP3A inducer cannot be avoided

  • As 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

Oral NINLARO is administered once a week for 3 weeks of a 4‑week cycle1

The usual recommended starting dose of NINLARO is one 4 mg capsule taken once a week based on the following schedule:1

NINLARO + Rd 28‑day dosing schedule1

Dosing Schedule

* The recommended starting dose of dexamethasone is 40 mg - each tablet contains 2 mg dexamethasone

Treatment with NINLARO in combination with Rd for longer than 24 cycles should be based on an individual benefit risk assessment1

  • The recommended starting dose of oral NINLARO is 3 mg for patients with moderate or severe hepatic impairment, severe renal impairment or end-stage renal disease requiring dialysis1
  • NINLARO should be taken with lenalidomide and dexamethasone at standard dosing1
    • 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
  • Prior to initiating a new cycle of therapy:1
    • Absolute neutrophil count should be ≥1000/mm3
    • Platelet count should be ≥75,000/mm3
    • Non-haematological 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
  • Antiviral prophylaxis should be considered to reduce the risk of herpes zoster reactivation
  • For additional information regarding lenalidomide or dexamethasone, please refer to each respective SmPC

Treatment with NINLARO in combination with lenalidomide and dexamethasone for longer than 24 cycles should be based on an individual benefit risk assessment1

How to administer NINLARO1

The usual recommended starting dose of oral NINLARO is one 4 mg capsule taken once a week with lenalidomide and dexamethasone at standard dosing1

Each dose of NINLARO should be taken approximately the same time each day on an empty stomach (at least 1 hour before or at least 2 hours after food)1 ‡

  • Because dexamethasone should be taken with food, NINLARO and dexamethasone should not be taken at the same time

NINLARO should be swallowed whole with a glass of water - the capsule should not be crushed, chewed or opened1

  • 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§

If a dose of NINLARO is delayed or missed, the dose should be taken only if the next scheduled dose is ≥72 hours away1

  • 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

NINLARO should be stored in the original packaging in order to protect from moisture¤ and the capsules should be removed just prior to dosing1 - this means they cannot be transferred to a pill box

Do not store above 30°C. Do not freeze1

NINLARO is cytotoxic - direct contact with the capsule contents should be avoided

Administration with a high-fat meal decreased ixazomib AUC by 28% compared with administration after an overnight fast

§ After oral administration, peak plasma concentrations of ixazomib were achieved at approximately one hour after dosing

¤ Ixazomib citrate, a prodrug, is a substance that rapidly hydrolyses under physiological conditions to its biologically active form, ixazomib

Oral NINLARO is available in several strengths to allow for dose modification1

NINLARO dose reduction steps1

  • 4 mg is the usual recommended starting dose1
  • No dose adjustment is required for:1
    • Body surface area or weight
    • Elderly patients older than 65 years
    • Patients with mild or moderate renal impairment (creatinine clearance ≥ 30mL/min)
    • Patients with mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 x ULN and any AST)
  • Use the recommended starting dose of 3 mg in patients with:1
    • moderate (total bilirubin > 1.5-3 x ULN) or severe (total bilirubin > 3 x ULN) hepatic impairment
    • severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease requiring dialysis#

#NINLARO is not dialyzable and, therefore, can be administered without regard to the timing of dialysis

Concomitant medicinal products1

  • Antiviral prophylaxis should be considered in patients being treated with NINLARO to decrease the risk of herpes zoster reactivation
  • Patients included in studies with 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 NINLARO in combination with lenalidomide and dexamethasone, and should be based on an assessment of the patient's underlying risks and clinical status
  • As NINLARO is administered in combination with lenalidomide and dexamethasone, refer to the SmPC for these medicinal products for additional concomitant medicinal products that may be required

Using NINLARO in special patient populations1

Elderly

  • No dose adjustment of NINLARO is required for patients over 65 years of age
  • Discontinuations in patients less than 75 years of age were reported in 13 patients (28%) in the NINLARO regimen and 10 patients (16%) in the placebo regimen
  • Discontinuations in patients over 75 years of age were observed in 10 patients (21%) in the NINLARO regimen and 9 patients (15%) in the placebo regimen

Paediatric population

  • NINLARO in combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with MM who have received at least one prior therapy
  • The safety and efficacy of NINLARO in children below 18 years of age have not been established - no data are available

Hepatic impairment

  • No dose adjustment of NINLARO is required for patients with mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 x ULN and any AST)
  • A lower starting dose of 3 mg is recommended for patients with moderate (total bilirubin >1.5 to 3 x ULN) or severe (total bilirubin >3 x ULN) hepatic impairment

Renal impairment

  • No dose adjustment of NINLARO is required for patients with mild or moderate renal impairment (creatinine clearance ≥30 mL/min)
  • A lower starting dose of 3 mg is recommended for patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease requiring dialysis
  • NINLARO is not dialysable and therefore can be administered without regard to the timing of dialysis
  • Refer to the lenalidomide SmPC for dosing recommendations in patients with renal impairment

NINLARO + Rd adverse events were generally Grade 1 or 2 and were manageable with supportive care1

For overlapping toxicities (thrombocytopenia, neutropenia and rash), the first dose reduction step is to reduce lenalidomide

For full dose modification recommendations please refer to the NINLARO Summary of Product Characteristics

Myelosuppression
  • Platelet counts should be monitored at least monthly during treatment with NINLARO - more frequent monitoring should be considered during the first three cycles as per the lenalidomide SmPC1,3
  • Manage thrombocytopenia and neutropenia with dose modification and platelet transfusions or G-CSF respectively, as per standard medical guidelines1
  • An alternating dose modification approach is recommended for NINLARO and lenalidomide for overlapping toxicities of thrombocytopenia and neutropenia
    Adverse Event Recommended Action1
    Thrombocytopenia (platelet count <30,000/mm3)

    and/or

    Neutropenia (absolute neutrophil count < 500/mm3)
    • Withhold NINLARO and lenalidomide until platelet or absolute neutrophil counts are ≥30,000/mm3 or ≥ 500/mm3, respectively
    • Following recovery, resume lenalidomide at the next lower dose according to its SmPC and resume NINLARO at the most recent dose
    • If platelet or absolute neutrophil counts drops again to <30,000/mm3 or < 500/mm3 respectively, withhold NINLARO and lenalidomide until recovery
    • Following recovery, resume NINLARO at the next lower dose, and resume lenalidomide at the most recent dose*

    * For additional occurrences, alternate dose modification of lenalidomide and NINLARO

Peripheral neuropathy
  • Patients on NINLARO should be monitored for symptoms of neuropathy, such as a burning sensation, hyperaesthesia, hypoaesthesia, paraesthesia, discomfort, neuropathic pain or weakness1
  • Patients experiencing new or worsening PN may require dose modification (see table below)1
  • Withhold treatment or adjust dosing for Grade 1 to 3 symptoms1
  • Discontinue treatment for Grade 4 symptoms1
    Adverse Event Recommended Action1
    Grade 1 PN with pain
    Grade 2 PN
    • Withhold NINLARO until PN recovers to ≤Grade 1 without pain or patient's baseline condition
    • Following recovery, resume NINLARO at the most recent dose
    Grade 2 PN with pain
    Grade 3 PN
    • Withhold NINLARO - toxicities should, at the physician's discretion, generally recover to patient's baseline condition or ≤Grade 1 prior to resuming NINLARO
    • Following recovery, resume NINLARO at the next lower dose
    Grade 4 PN
    • Discontinue treatment regimen
Rash
  • Rash has been most commonly characterised as maculo-papular or macular and is most commonly reported within the first 3 cycles of therapy1,5
  • Symptomatic measures such as antihistamines or corticosteroids (oral or topical) have been used successfully to manage rash and have been used prophylactically in subsequent cycles during NINLARO clinical studies6
  • The use of a topical, IV or oral steroid (e.g. prednisolone ≤10 mg per day or equivalent) was permitted within the TOURMALINE‑MM1 study6
  • Manage rash with supportive care and/or with dose modification if Grade 2 or 31
  • Discontinue treatment if Grade 4 symptoms1
    Adverse Event Recommended Action1
    Grade 2 or 3 rash
    • Withhold lenalidomide until rash recovers to ≤Grade 1
    • Following recovery, resume lenalidomide at the next lower dose according to its SmPC
    • If Grade 2 or 3 rash occurs again, withhold NINLARO and lenalidomide until rash recovers to ≤Grade 1
    • Following recovery, resume NINLARO at the next lower dose and resume lenalidomide at its most recent dose
    Grade 4
    • Discontinue treatment regimen

    Grading based on National Cancer Institute Common Terminology Criteria (CTCAE) Version 4.03

    For additional occurrences, alternate dose modification of lenalidomide and NINLARO

Gastrointestinal toxicities
  • Reversible diarrhoea, nausea, vomiting, decreased appetite and constipation have been reported in clinical studies1,2
  • Patients should be monitored for gastrointestinal toxicity and should be given appropriate supportive care1,2
  • Standard anti-emetics including 5‑HT 3 antagonists are recommended according to clinical practice for emesis if it occurs once treatment is initiated - prophylactic anti-emetics may also be considered at the physician's discretion6
  • Dexamethasone should not be administered as an anti-emetic6
  • Prophylactic antidiarrhoeals are not recommended; however diarrhoea should be managed according to standard clinical practice, including the administration of antidiarrhoeals once infectious causes are excluded6
  • Fluid deficits should be corrected before initiation of NINLARO and as needed during treatment to avoid dehydration6
    Adverse Event Recommended Action1
    Grade 3 or 4 gastrointestinal toxicities
    • Withhold NINLARO - toxicities should, at the physician's discretion, generally recover to patient's baseline condition or ≤Grade 1 prior to resuming NINLARO
    • If attributable to NINLARO, resume NINLARO at the next lower dose following recovery
  • In the case of severe gastrointestinal events, monitoring of serum potassium level is recommended1
  • For lenalidomide-related toxicity, refer to the lenalidomide SmPC for dose adjustments
Other non-haematological toxicities
Adverse Event Recommended Action1
Other Grade 3 or 4 non haematological toxicities
  • Withhold NINLARO - toxicities should, at the physician's discretion, generally recover to patient's baseline condition or ≤Grade 1 prior to resuming NINLARO
  • If attributable to NINLARO, resume NINLARO at the next lower dose following recovery
  • For lenalidomide- and dexamethasone-related toxicities, refer to the lenalidomide or dexamethasone SmPCs for dose adjustments

NINLARO Patient Support Programme (PSP)

This NINLARO Patient Support Programme (PSP) has been designed to help patient familiarise themselves with the NINLARO based triplet regimen. The programme is intended for patients that are currently receiving or are about to initiate treatment with the NINLARO regimen.

To download a copy of the booklet, which provides further information on the programme for Healthcare Professional click here