SIGNIFOR-LAR SIDE EFFECTS
- Generic Name: pasireotide for injectable suspension, for intramuscular use
- Brand Name: Signifor-LAR
SIDE EFFECTS
Clinically significant adverse reactions that appear in other sections of the labeling include:
- Hyperglycemia and Diabetes
- Bradycardia and QT Prolongation
- Liver Test Elevations
- Cholelithiasis
- Pituitary Hormone Deficiency(ies)
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
Drug-Naive Patients With Acromegaly
The data described in Table 1 are derived from an active-controlled trial in patients with acromegaly naive to previous drug therapy. The data reflect exposure of 178 patients with acromegaly to SIGNIFOR LAR for a mean duration of 43 weeks. In the overall study population, 52% were female and the average age of patients was 45 years. Additional information on design and demographics of this trial are described below.
Table 1 presents common adverse reactions associated with SIGNIFOR LAR. These adverse reactions were not present at baseline or, if present, worsened from baseline and occurred in at least 5% of patients treated with SIGNIFOR LAR.
Table 1 : Adverse Reactions Occurring in ≥ 5% of Patients Exposed to SIGNIFOR LAR in Patients with Acromegaly Naive to Drug Therapy
| Adverse Reaction Type | SIGNIFOR LAR (40-60 mg) % N=178 |
Active Comparator % N=180 |
| Hyperglycemia Related Adverse Reactions | ||
| Hyperglycemia | 29 | 8 |
| Diabetes mellitus* | 26 | 4 |
| Blood glucose increased | 8 | 2 |
| Glycosylated hemoglobin increased | 6 | 2 |
| Hypoglycemia | 5 | 7 |
| Gastrointestinal Related Adverse Reactions | ||
| Diarrhea | 39 | 45 |
| Abdominal pain | 18 | 22 |
| Nausea | 14 | 22 |
| Abdominal distension | 12 | 12 |
| Vomiting | 8 | 7 |
| Abdominal pain upper | 6 | 8 |
| Hepatobiliary Related Adverse Reactions | ||
| Cholelithiasis | 26 | 36 |
| Cardiac Related Adverse Reactions | ||
| Sinus bradycardia** | 10 | 7 |
| Hypertension | 8 | 7 |
| Nervous System Related Adverse Reactions | ||
| Headache | 19 | 26 |
| Dizziness | 10 | 11 |
| Skin Related Adverse Reactions | ||
| Alopecia | 18 | 19 |
| Infections Related Adverse Reactions | ||
| Nasopharyngitis | 16 | 16 |
| Influenza | 8 | 4 |
| Upper respiratory tract infection | 7 | 3 |
| Cough | 5 | 8 |
| Laboratory Related Adverse Reactions | ||
| Blood creatine phosphokinase increased | 13 | 12 |
| Alanine aminotransferase increased | 8 | 4 |
| Aspartate aminotransferase increased | 6 | 4 |
| Weight decreased | 5 | 4 |
| General and Injection Site Related Adverse Reactions | ||
| Fatigue | 10 | 10 |
| Injection site reaction*** | 7 | 7 |
| Musculoskeletal and Connective Tissue Related Adverse Reactions | ||
| Arthralgia | 10 | 12 |
| Back pain | 8 | 11 |
| Pain in extremity | 7 | 4 |
| Blood Related Adverse Reactions | ||
| Anemia | 6 | 6 |
| *Diabetes mellitus includes the following PTs: Diabetes mellitus and type 2 diabetes mellitus **Sinus bradycardia includes the following PTs: Bradycardia and sinus bradycardia ***Injection site reaction related AEs includes the following PTs: Injection site pain, Injection site reaction, Injection site haematoma, Injection site pruritus, Injection site swelling, Injection site erythema |
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Other notable adverse reactions which occurred with a frequency of 5% or less for SIGNIFOR LAR were: adrenal insufficiency (3%); glucose tolerance impaired (1%); QT-prolongation (4%); blood amylase increased (2%).
Patients With Acromegaly Inadequately Controlled On Other Somatostatin Analogs At Baseline
The data described in Table 2 are derived from an active-controlled study in patients with acromegaly inadequately controlled at baseline on other somatostatin analogs. These data reflect exposure of 63 and 62 patients to SIGNIFOR LAR 40 mg and 60 mg, respectively, for a mean duration of 24 weeks.
In the overall study population, 56% were female and the average age of patients was 45 years. Additional information on design and demographics of this trial are described below.
Table 2 presents common adverse reactions associated with SIGNIFOR LAR. These common adverse reactions were not present at baseline or, if present, worsened from baseline and occurred in at least 5% of patients treated with SIGNIFOR LAR.
Table 2 : Adverse Reactions Occurring in ≥ 5% of Patients Exposed to SIGNIFOR LAR in Patients with Acromegaly Previously Treated with Other Somatostatin Analogs
| Adverse Drug Reactions | SIGNIFOR LAR 40 mg % N=63 |
SIGNIFOR LAR 60 mg % N=62 |
Active Comparators % N=66 |
| Hyperglycemia Related Adverse Reactions | |||
| Hyperglycemia | 33 | 30 | 14 |
| Diabetes mellitus* | 21 | 31 | 9 |
| Blood glucose increased | 5 | 7 | 0 |
| Hypoglycemia | 3 | 7 | 0 |
| Gastrointestinal Related Adverse Reactions | |||
| Diarrhea | 16 | 19 | 5 |
| Abdominal pain | 8 | 8 | 3 |
| Nausea | 3 | 7 | 3 |
| Hepatobiliary Related Adverse Reactions | |||
| Cholelithiasis | 10 | 13 | 14 |
| Cardiac Related Adverse Reactions | |||
| Atrioventricular block first degree | 6 | 0 | 0 |
| Nervous System Related Adverse Reactions | |||
| Headache | 14 | 3 | 5 |
| Dizziness | 8 | 2 | 3 |
| Skin and Subcutaneous Tissue Related Adverse Reactions | |||
| Alopecia | 2 | 7 | 0 |
| Infections Related Adverse Reactions | |||
| Nasopharyngitis | 6 | 11 | 3 |
| Blood Related Adverse Reactions | |||
| Anemia | 6 | 3 | 3 |
| * Diabetes mellitus includes the following PTs: diabetes mellitus and type 2 diabetes mellitus | |||
Other notable adverse reactions which occurred with a frequency of 5% or less in the SIGNIFOR LAR 40 mg, SIGNIFOR LAR 60 mg arm, respectively, were adrenal insufficiency (2% and 0%) and glucose tolerance impaired (3% and 5%).
Hyperglycemia
*Numbers of patients with a glucose value at the given timepoint in the SIGNIFOR LAR/Active comparator arms are displayed as xxx/xxx on the x axis
Pancreatic Enzyme Elevation And Pancreatitis
Asymptomatic, elevations in lipase and alpha amylase were observed in 30% and 20% of patients receiving SIGNIFOR LAR in the drug naive study and in 1% and 3% of patients receiving SIGNIFOR LAR in the study of patients previously treated. In the drug-naive study, 2 patients receiving SIGNIFOR LAR developed pancreatitis. Pancreatitis is a potential adverse reaction associated with the use of SIGNIFOR LAR due to the association between cholelithiasis and acute pancreatitis.
SRC: NLM .