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Soliris

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Soliris

Side Effects
Interactions

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

  • Serious Meningococcal Infections [See WARNINGS AND PRECAUTIONS]
  • Other Infections [See WARNINGS AND PRECAUTIONS]
  • Monitoring Disease Manifestations After Soliris Discontinuation [See WARNINGS AND PRECAUTIONS]
  • Thrombosis Prevention and Management [See WARNINGS AND PRECAUTIONS]
  • Infusion Reactions [See WARNINGS AND PRECAUTIONS]

Clinical Trial 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.

Meningococcal infections are the most important adverse reactions experienced by patients receiving Soliris. In PNH clinical studies, two patients experienced meningococcal sepsis. Both patients had previously received a meningococcal vaccine. In clinical studies among patients without PNH, meningococcal meningitis occurred in one unvaccinated patient. Meningococcal sepsis occurred in one previously vaccinated patient enrolled in the retrospective aHUS study during the post-study follow-up period [see WARNINGS AND PRECAUTIONS].

PNH

The data described below reflect exposure to Soliris in 196 adult patients with PNH, age 18-85, of whom 55% were female. All had signs or symptoms of intravascular hemolysis. Soliris was studied in a placebo-controlled clinical study (in which 43 patients received Soliris and 44, placebo); a single arm clinical study and a long term extension study. 182 patients were exposed for greater than one year. All patients received the recommended Soliris dose regimen. Table 4 summarizes the adverse reactions that occurred at a numerically higher rate in the Soliris group than the placebo group and at a rate of 5% or more among patients treated with Soliris.

Table 4: Adverse Reactions Reported in 5% or More of Soliris Treated Patients and Greater than Placebo in the Controlled Clinical Study

Reaction Soliris
N = 43
N (%)
Placebo
N = 44
N (%)
Headache 19 (44) 12 (27)
Nasopharyngitis 10 (23) 8 (18)
Back pain 8 (19) 4 (9)
Nausea 7 (16) 5 (11)
Fatigue 5 (12) 1 (2)
Cough 5 (12) 4 (9)
Herpes simplex infections 3 (7) 0
Sinusitis 3 (7) 0
Respiratory tract infection 3 (7) 1 (2)
Constipation 3 (7) 2 (5)
Myalgia 3 (7) 1 (2)
Pain in extremity 3 (7) 1 (2)
Influenza-like illness 2 (5) 1 (2)

In the placebo-controlled clinical study, serious adverse reactions occurred among 4 (9%) patients receiving Soliris and 9 (21%) patients receiving placebo. The serious reactions included infections and progression of PNH. No deaths occurred in the study and no patients receiving Soliris experienced a thrombotic event; one thrombotic event occurred in a patient receiving placebo.

Among 193 patients with PNH treated with Soliris in the single arm, clinical study or the follow-up study, the adverse reactions were similar to those reported in the placebo-controlled clinical study. Serious adverse reactions occurred among 16% of the patients in these studies. The most common serious adverse reactions were: viral infection (2%), headache (2%), anemia (2%), and pyrexia (2%).

aHUS

The safety of Soliris therapy in patients with aHUS was evaluated in four prospective, single-arm studies, three in adult and adolescent patients (aHUS Studies 1, 2, and 4), one in pediatric and adolescent patients (aHUS Study 5) and one retrospective study (aHUS Study 3).

The data described below were derived from 78 adult and adolescent patients with aHUS enrolled in aHUS Study 1, aHUS Study 2, and aHUS Study 4. All patients received the recommended dosage of Soliris. Median exposure was 67 weeks (range: 2-145 weeks). Table 5 summarizes all adverse events reported in at least 10% of patients in aHUS Studies 1, 2, and 4 combined.

Table 5: Per Patient Incidence of Adverse Events in 10% or More Adult and Adolescent Patients Enrolled in aHUS Study 1, aHUS Study 2 and aHUS Study 4 Separately and in Total

MedDRA ver. 15.1 Number (%) of Patients
Study 1
(n=17)
Study 2
(n=20)
Study 4
(n=41)
Total
(n=78)
Vascular Disorders
  Hypertensiona 10 (59) 9 (45) 7 (17) 26 (33)
  Hypotension 2 (12) 4 (20) 7 (17) 13 (17)
Infections and Infestations
  Bronchitis 3 (18) 2 (10) 4 (10) 9 (12)
  Nasopharyngitis 3 (18) 11 (55) 7 (17) 21 (27)
  Gastroenteritis 3 (18) 4 (20) 2 (5) 9 (12)
  Upper respiratory tract infection 5 (29) 8 (40) 2 (5) 15 (19)
  Urinary tract infection 6 (35.3) 3 (15) 8 (20) 17 (22)
Gastrointestinal Disorders
  Diarrhea 8 (47) 8 (40) 12 (32) 29 (37)
  Vomiting 8 (47) 9 (45) 6 (15) 23 (30)
  Nausea 5 (29) 8 (40) 5 (12) 18 (23)
  Abdominal pain 3 (18) 6 (30) 6 (15) 15 (19)
Nervous System Disorders
  Headache 7 (41) 10 (50) 15 (37) 32 (41)
Blood and Lymphatic System Disorders
  Anemia 6 (35) 7 (35) 7 (17) 20 (26)
  Leukopenia 4 (24) 3 (15) 5 (12) 12 (15)
Psychiatric Disorders
  Insomnia 4 (24) 2 (10) 5 (12) 11 (14)
Renal and Urinary Disorders
  Renal Impairment 5 (29) 3 (15) 6 (15) 14 (18)
  Proteinuria 2 (12) 1 (5) 5 (12) 8 (10)
Respiratory, Thoracic and Mediastinal Disorders
  Cough 4 (24) 6 (30) 8 (20) 18 (23)
General Disorders and Administration Site Conditions
  Fatigue 3 (18) 4 (20) 3 (7) 10 (13)
  Peripheral edema 5 (29) 4 (20) 9 (22) 18 (23)
  Pyrexia 4 (24) 5 (25) 7 (17) 16 (21)
  Asthenia 3 (18) 4 (20) 6 (15) 13 (17)
  Eye Disorder 5 (29) 2 (10) 8 (20) 15 (19)
Metabolism and Nutrition Disorders
  Hypokalaemia 3 (18) 2 (10) 4 (10) 9 (12)
  Neoplasms benign, malignant, and unspecified (including cysts and polyps) 1 (6) 6 (30) 1 (20) 8 (10)
Skin and Subcutaneous Tissue Disorders
  Rash 2 (12) 3 (15) 6 (15) 11 (14)
  Pruritis 1 (6) 3 (15) 4 (10) 8 (10)
Musculoskeletal and Connective Tissue Disorders
  Arthralgia 1 (6) 2 (10) 7 (17) 10 (13)
  Back pain 3 (18) 3 (15) 2 (5) 8 (10)
a includes the preferred terms hypertension, accelerated hypertension, and malignant hypertension.

In aHUS Studies 1, 2, and 4 combined, 60% (47/78) of patients experienced a serious adverse event (SAE). The most commonly reported SAEs were infections (24%), hypertension (5%), chronic renal failure (5%), and renal impairment (5%). Five patients discontinued Soliris due to adverse events; three due to worsening renal function, one due to new diagnosis of Systemic Lupus Erythematosus, and one due to meningoccal meningitis.

aHUS Study 5 included 22 pediatric and adolescent patients, of which 18 patients were less than 12 years of age. All patients received the recommended dosage of Soliris. Median exposure was 44 weeks (range: 1 dose-87 weeks). Table 6 summarizes all adverse events reported in at least 10% of patients enrolled in aHUS Study 5.

Table 6: Per Patient Incidence of Adverse Reactions in 10% or More Patients Enrolled in aHUS Study 5

MedDRA ver. 15.1 1 month to < 12 yrs
(n=18)
Total
(n=22)
Eye Disorders 3 (17) 3 (14)
Gastrointestinal Disorders
  Abdominal pain 6 (33) 7 (32)
  Diarrhoea 5 (28) 7 (32)
  Vomiting 4 (22) 6 (27)
  Dyspepsia 0 3 (14)
General Disorders and Administration Site Conditions
  Pyrexia 9 (50) 11 (50)
Infections and Infestations
  Upper respiratory tract infection 5 (28) 7 (32)
  Nasopharyngitis 3 (17) 6 (27)
  Rhinitis 4 (22) 4 (18)
  Urinary Tract infection 3 (17) 4 (18)
  Catheter site infection 3 (17) 3 (14)
Musculoskeletal and Connective Tissue Disorders
  Muscle spasms 2 (11) 3 (14)
Nervous System Disorders
  Headache 3 (17) 4 (18)
  Renal and Urinary Disorders 3 (17) 4 (18)
Respiratory, Thoracic and Mediastinal Disorders
  Cough 7 (39) 8 (36)
  Oropharyngeal pain 1 (6) 3 (14)
Skin and Subcutaneous Tissue Disorders
  Rash 4 (22) 4 (18)
Vascular Disorders
  Hypertension 4 (22) 4 (18)

In aHUS Study 5, 59% (13/22) of patients experienced a serious adverse event (SAE). The most commonly reported SAEs were hypertension (9%), viral gastroenteritis (9%), pyrexia (9%), and upper respiratory infection (9%). One patient discontinued Soliris due to an adverse event (severe agitation).

Analysis of retrospectively collected adverse event data from pediatric and adult patients enrolled in aHUS Study 3 (N=30) revealed a safety profile that was similar to that which was observed in the two prospective studies. aHUS Study 3 included 19 pediatric patients less than 18 years of age. Overall, the safety of Soliris in pediatric patients with aHUS enrolled in Study 3 appeared similar to that observed in adult patients. The most common ( ≥ 15%) adverse events occurring in pediatric patients are presented in Table 7.

Table 7: Adverse Reactions Occurring in at Least 15% of Patients Less than 18 Years of Age Enrolled in aHUS Study 3

MedDRA ver. 11.0 Number (%) of Patients
< 2 yrs
(n=5)
2 to < 12 yrs
(n=10)
12 to < 18 yrs
(n=4)
Total
(n=19)
General Disorders and Administration Site Conditions
  Pyrexia 4 (80) 4 (40) 1 (25) 9 (47)
Gastrointestinal Disorders
  Diarrhea 1 (20) 4 (40) 1 (25) 6 (32)
  Vomiting 2 (40) 1 (10) 1 (25) 4 (21)
Infections and Infestations
  Upper respiratory tract infectiona 2 (40) 3 (30) 1 (25) 6 (32)
Respiratory, Thoracic and Mediastinal Disorders
  Cough 3 (60) 2 (20) 0 (0) 5 (26)
  Nasal congestion 2 (40) 2 (20) 0 (0) 4 (21)
Cardiac Disorders
  Tachycardia 2 (40) 2 (20) 0 (0) 4 (21)
a includes the preferred terms upper respiratory tract infection and nasopharyngitis.

Immunogenicity

As with all proteins, there is a potential for immunogenicity with eculizumab. The immunogenicity of Soliris has been evaluated using two different immunoassays for the detection of anti-eculizumab antibodies: a direct enzyme-linked immunosorbent assay (ELISA) using the Fab fragment of eculizumab as target was used for the PNH indication; and an electro-chemiluminescence (ECL) bridging assay using the eculizumab whole molecule as target was used for the aHUS indication, as well as for additional patients with PNH. In the PNH population, antibodies to Soliris were detected in 3/196 (2%) patients with PNH treated with Soliris using the ELISA assay and in 5/161 (3%) patients treated with Soliris using the ECL assay. In patients with aHUS treated with Soliris, antibodies to Soliris were detected in 3/100 (3%) using the ECL assay. An ECL based neutralizing HAHA assay with a low sensitivity of 2 mcg/mL was performed to detect neutralizing antibodies for the 3 patients with aHUS and also for the 5 patients with PNH with positive samples using the ECL assay. 2/161 patients in the PNH group (1.2%) and 1/100 patients in the aHUS group (1%) had low positive values for neutralizing antibodies. No apparent correlation of antibody development to clinical response was observed in either indication. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to Soliris in an ELISA-based assay and/or an ECL-based assay and are highly dependent on the sensitivity and specificity of the assay used. Additionally, the observed incidence of antibody positivity in the assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Soliris with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Soliris. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Soliris exposure.

Cases of serious or fatal meningococcal infections have been reported.

Read the Soliris (eculizumab) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Drug interaction studies have not been performed with Soliris.

Last reviewed on RxList: 5/20/2014
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
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Soliris - User Reviews

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