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Ninlaro is a brand name for Ixazomib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: NINLARO 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.
Verbatim from this product's EMA label. Tap a section to expand.
Treatment must be initiated and monitored under the supervision of a physician experienced in the management of multiple myeloma. 3 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 = intake of medicinal product 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.
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.
3 mg *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. 28-day cycle (a 4-week cycle) Week 1 Week 2 Week 3 Week 4 Day 1 Days 2 to 7 Day 8 Days 9 to 14 Day 15 Days 16 to 21 Day 22 Days 23 to 28 Ixazomib Lenalidomide Daily Daily Daily Dexamethasone 4 An alternating dose modification approach is recommended for ixazomib and lenalidomide for overlapping toxicities of thrombocytopenia, neutropenia and rash.
As ixazomib is administered in combination with lenalidomide and dexamethasone, refer to the SmPC for these medicinal products for additional undesirable effects. Summary of the safety profile The safety profile of NINLARO is based on available clinical trial data and post-marketing experience to date.
Frequencies of adverse reactions described below and in Table 3 have been determined based on data generated from clinical studies. Unless otherwise noted, the data presented below is the pooled safety data from the pivotal, Phase 3, global C16010 study (n = 720) and the double-blind, placebo-controlled C16010 China Continuation Study (n = 115).
The most frequently reported adverse reactions (≥ 20%) across 418 patients treated within the ixazomib regimen and 417 patients within the placebo regimen were diarrhoea (47% vs. 38%), thrombocytopenia (41% vs. 24%), neutropenia (37% vs.
36%), constipation (31% vs. 24%), upper respiratory tract infection (28% vs. 24%), peripheral neuropathy (28% vs. 22%), nausea (28% vs. 20%), back pain (25% vs. 21%), rash (25% vs. 15%), peripheral oedema (24% vs. 19%), vomiting 10 (23% vs.
12%) and bronchitis (20% vs. 15%). Serious adverse reactions reported in ≥ 2% of patients included diarrhoea (3%), thrombocytopenia (2%) and bronchitis (2%). Tabulated list of adverse reactions The following convention is used for the classification of the frequency of an adverse drug reaction (ADR): very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Within each system organ class, the ADRs are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
As ixazomib is administered in combination with lenalidomide and dexamethasone, refer to the SmPC for these medicinal products for additional special warnings and precautions for use. 8). Platelet counts should be monitored at least monthly during ixazomib treatment.
More frequent monitoring should be considered during the first three cycles as per the lenalidomide SmPC. 2) and platelet transfusions as per standard medical guidelines. 8). 2). In case of severe gastrointestinal events, monitoring of serum potassium level is recommended.
8). The patient should be monitored for symptoms of peripheral neuropathy. 2). 8). The patient should be evaluated for underlying causes and provide supportive care, as necessary. 2). 8). 2). 8). At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions.
If signs and symptoms suggestive of these reactions appear, ixazomib should be withdrawn immediately and an alternative treatment considered (as appropriate). If the patient has developed a serious reaction such as SJS or TEN with the use of ixazomib, treatment with ixazomib must not be restarted in this patient at any time.
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.
8). 2). Pregnancy Women should avoid becoming pregnant while being treated with ixazomib. If ixazomib is used during pregnancy or if the patient becomes pregnant while taking ixazomib, the patient should be apprised of the potential hazard to the foetus.
1. As ixazomib is administered in combination with lenalidomide and dexamethasone, refer to the SmPC for these medicinal products for additional contraindications.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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For these toxicities, the first dose modification step is to withhold/reduce lenalidomide. 2 for the dose reduction steps for these toxicities.
Table 2:
Dose modifications guidelines for ixazomib in combination with lenalidomide and dexamethasone Haematological toxicities Recommended actions Thrombocytopenia (platelet count) Platelet count < 30 000/mm3 • Withhold ixazomib and lenalidomide until platelet count ≥ 30 000/mm3.
• Following recovery, resume lenalidomide at the next lower dose according to its SmPC and resume ixazomib at its most recent dose. • If platelet count falls to < 30 000/mm3 again, withhold ixazomib and lenalidomide until platelet count ≥ 30 000/mm3.
* Neutropenia (absolute neutrophil count) Absolute neutrophil count < 500/mm3 • Withhold ixazomib and lenalidomide until absolute neutrophil count is ≥ 500/mm3. Consider adding G-CSF as per clinical guidelines. • Following recovery, resume lenalidomide at the next lower dose according to its prescribing information and resume ixazomib at its most recent dose.
• If absolute neutrophil count falls to < 500/mm3 again, withhold ixazomib and lenalidomide until absolute neutrophil count is ≥ 500/mm3. * Non-haematological toxicities Recommended actions Rash Grade† 2 or 3 • 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 ixazomib and lenalidomide until rash recovers to ≤ Grade 1. * Grade 4 Discontinue treatment regimen.
Peripheral neuropathy Grade 1 peripheral neuropathy with pain or Grade 2 peripheral neuropathy • Withhold ixazomib until peripheral neuropathy recovers to ≤ Grade 1 without pain or patient's baseline. • Following recovery, resume ixazomib at its most recent dose.
Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy • Withhold ixazomib. Toxicities should, at the physician’s discretion, generally recover to patient’s baseline condition or ≤ Grade 1 prior to resuming ixazomib.
• Following recovery, resume ixazomib at the next lower dose. Grade 4 peripheral neuropathy Discontinue treatment regimen. 5 Table 2: Dose modifications guidelines for ixazomib in combination with lenalidomide and dexamethasone Other non-haematological toxicities Other Grade 3 or 4 non-haematological toxicities • Withhold ixazomib.
Toxicities should, at the physician’s discretion, generally recover to patient’s baseline condition or at most Grade 1 prior to resuming ixazomib. • If attributable to ixazomib, resume ixazomib at the next lower dose following recovery.
03 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 […]
Table 3:
Adverse reactions in patients treated with ixazomib in combination with lenalidomide and dexamethasone (all grades, grade 3 and grade 4) System organ class / Adverse reaction Adverse reactions (all grades) Grade 3 adverse reactions Grade 4 adverse reactions Infections and infestations Upper respiratory tract infection Very common Common Bronchitis Very common Common Herpes zoster Common Common Blood and lymphatic system disorders Thrombocytopenia* Very common Very common Common Neutropenia* Very common Very common Common Thrombotic microangiopathy Rare Rare Thrombotic thrombocytopenic purpura† Rare Rare Rare Immune system disorders Anaphylactic reaction† Rare Very rare Very rare Angioedema† Rare Rare Metabolism and nutrition disorders Tumour lysis syndrome† Rare Rare Rare Nervous system disorders Peripheral neuropathies* Very common Common Posterior reversible encephalopathy disorders*† Rare Rare Rare Transverse myelitis† Rare Rare Gastrointestinal disorders Diarrhoea Very common Common Constipation Very common Uncommon Nausea Very common Common Vomiting Very common Uncommon Skin and subcutaneous tissue disorders Rash* Very common Common Stevens-Johnson syndrome† Rare Rare Acute febrile neutrophilic dermatosis Rare Rare Toxic epidermal necrolysis† Rare Rare Musculoskeletal and connective tissue disorders Back pain Very common Uncommon Arthralgia Very common Common 11 System organ class / Adverse reaction Adverse reactions (all grades) Grade 3 adverse reactions Grade 4 adverse reactions General disorders and administration site conditions Oedema peripheral Very common Common Pyrexia Very common Uncommon *Represents a pooling of preferred terms †Reported outside of the Phase 3 studies Description of selected adverse reactions Discontinuations For each adverse reaction, one or more of the three medicinal products was discontinued in ≤ 3% of patients in the ixazomib regimen.
Thrombocytopenia Two percent of patients in both the ixazomib regimen and the placebo regimen had a platelet count ≤ 10 000/mm3 during treatment. Less than 1% of patients in both regimens had a platelet count ≤ 5 000/mm3 during treatment.
Thrombocytopenia resulted in discontinuation of one or more of the three medicinal products in 2% of patients in the ixazomib regimen and 3% of patients in the placebo regimen. Thrombocytopenia did not result in an increase in haemorrhagic events or platelet transfusions.
Gastrointestinal toxicities Diarrhoea resulted in discontinuation of one or more of the three medicinal products in 2% of patients in the ixazomib regimen and 1% of patients in the placebo regimen. Rash Rash occurred in 25% of patients in the ixazomib regimen compared to 15% of patients in the placebo regimen.
The most common type of rash reported in both regimens was maculo-papular and macular rash. Grade 3 rash was reported in 3% of patients in the ixazomib regimen compared to 2% of patients in the placebo regimen. Rash resulted in discontinuation of one or more of the three medicinal products in < 1% of patients in both regimens.
Peripheral neuropathy Peripheral neuropathy occurred in 28% of patients in the ixazomib regimen compared to 22% of patients in the placebo regimen. Grade 3 adverse reactions of peripheral neuropathy were reported in 2% of patients in the ixazomib regimen compared to 1% in the placebo regimen.
The most commonly reported reaction was peripheral sensory neuropathy (21% and 15% in the ixazomib and placebo regimen, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three medicinal products in 3% of patients in the ixazomib regimen compared to < 1% of patients in the placebo regimen.
Eye disorders Eye disorders were reported with many different preferred terms but in aggregate, the frequency was 34% in patients in the ixazomib regimen and 28% of patients in the placebo regimen. The most common adverse reactions were blurred vision (6% in the ixazomib regimen and 5% in the placebo regimen), dry eye (6% in the ixazomib regimen and 1% in the placebo regimen), conjunctivitis […]
6). Women using hormonal contraceptives should additionally use a barrier method of contraception. Posterior reversible encephalopathy syndrome Posterior reversible encephalopathy syndrome (PRES) has occurred in patients receiving ixazomib.
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. Strong CYP3A inducers Strong inducers may reduce the efficacy of ixazomib, therefore the concomitant use of strong CYP3A inducers such as carbamazepine, phenytoin, rifampicin and St.
2). Closely monitor patients for disease control if co-administration with a strong CYP3A inducer cannot be avoided. 8