NINLARO SIDE EFFECTS
SIDE EFFECTS
The following adverse reactions are described in detail in other sections of the prescribing information:
- Thrombocytopenia
- Gastrointestinal Toxicities
- Peripheral Neuropathy
- Peripheral Edema
- Cutaneous Reactions
- Thrombotic Microangiopathy
- Hepatotoxicity
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety population from the randomized, double-blind, placebo-controlled clinical study included 720 patients with relapsed and/or refractory multiple myeloma, who received NINLARO in combination with lenalidomide and dexamethasone (NINLARO regimen; N=360) or placebo in combination with lenalidomide and dexamethasone (placebo regimen; N=360).
The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen and greater than the placebo regimen were diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, and back pain. Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.
Table 1 summarizes the adverse reactions occurring in at least 5% of patients with at least a 5% difference between the NINLARO regimen and the placebo regimen.
Table 1: Non-Hematologic Adverse Reactions Occurring in ≥ 5% of Patients with a ≥ 5% Difference Between the NINLARO Regimen and the Placebo Regimen (All Grades, Grade 3 and Grade 4)
| System Organ Class / Preferred Term | NINLARO + Lenalidomide and Dexamethasone N=360 |
Placebo + Lenalidomide and Dexamethasone N=360 |
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| N (%) | N (%) | |||||
| All | Grade 3 | Grade 4 | All | Grade 3 | Grade 4 | |
| Infections and infestations | ||||||
| Upper respiratory tract infection | 69 (19) | 1 (< 1) | 0 | 52 (14) | 2 (< 1) | 0 |
| Nervous system disorders | ||||||
| Peripheral neuropathies* | 100 (28) | 7 (2) | 0 | 77 (21) | 7 (2) | 0 |
| Gastrointestinal disorders | ||||||
| Diarrhea | 151 (42) | 22 (6) | 0 | 130 (36) | 8 (2) | 0 |
| Constipation | 122 (34) | 1 (< 1) | 0 | 90 (25) | 1 (< 1) | 0 |
| Nausea | 92 (26) | 6 (2) | 0 | 74 (21) | 0 | 0 |
| Vomiting | 79 (22) | 4 (1) | 0 | 38 (11) | 2 (< 1) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Rash* | 68 (19) | 9 (3) | 0 | 38 (11) | 5 (1) | 0 |
| usculoskeletal and connective tissue disorders | ||||||
| Back pain | 74 (21) | 2 (< 1) | 0 | 57 (16) | 9 (3) | 0 |
| General disorders and administration site conditions | ||||||
| Edema peripheral | 91 (25) | 8 (2) | 0 | 66 (18) | 4 (1) | 0 |
| Note: Adverse reactions included as preferred terms are based on MedDRA version 16.0. *Represents a pooling of preferred terms |
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Table 2 represents pooled information from adverse event and laboratory data.
Table 2: Thrombocytopenia and Neutropenia
| NINLARO + Lenalidomide and Dexamethasone N=360 |
Placebo + Lenalidomide and Dexamethasone N=360 |
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| N (%) | N (%) | |||
| Any Grade | Grade 3-4 | Any Grade | Grade 3-4 | |
| Thrombocytopenia | 281 (78) | 93 (26) | 196 (54) | 39 (11) |
| Neutropenia | 240 (67) | 93 (26) | 239 (66) | 107 (30) |
Herpes Zoster
Herpes zoster was reported in 4% of patients in the NINLARO regimen and 2% of patients in the placebo regimen. Antiviral prophylaxis was allowed at the healthcare provider’s discretion. Patients treated in the NINLARO regimen who received antiviral prophylaxis had a lower incidence (< 1%) of herpes zoster infection compared to patients who did not receive prophylaxis (6%).
Eye Disorders
Eye disorders were reported with many different preferred terms but in aggregate, the frequency was 26% in patients in the NINLARO regimen and 16% of patients in the placebo regimen. The most common adverse reactions were blurred vision (6% in the NINLARO regimen and 3% in the placebo regimen), dry eye (5% in the NINLARO regimen and 1% in the placebo regimen), and conjunctivitis (6% in the NINLARO regimen and 1% in the placebo regimen). Grade 3 adverse reactions were reported in 2% of patients in the NINLARO regimen and 1% in the placebo regimen.
Adverse Reactions Reported Outside Of The Randomized Controlled Trial
The following serious adverse reactions have each been reported at a frequency of < 1%: acute febrile neutrophilic dermatosis (Sweet’s syndrome), Stevens-Johnson syndrome, transverse myelitis, posterior reversible encephalopathy syndrome, tumor lysis syndrome, and thrombotic thrombocytopenic purpura.
SRC: NLM .