Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Hypocortisolism [see Warnings and Precautions (5.1)] Hyperglycemia and Diabetes [see Warnings and Precautions (5.2)] Bradycardia and QT prolongation [see Warnings and Precautions (5.3)] Liver Test Elevations [see Warnings and Precautions (5.4)] Cholelithiasis and Complications of Cholelithiasis [see Warnings and Precautions (5.5)] Pituitary Hormone Deficiency [see Warnings and Precautions (5.6)] Steatorrhea and Malabsorption of Dietary Fats [see Warnings and Precautions (5.7) ] Most common adverse reactions occurring in ≥ 20% of patients are diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes mellitus ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases at 1-888-575-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 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.
A total of 162 Cushing's disease patients were exposed to SIGNIFOR in the Phase III study [see Clinical Studies (14)] .
At study entry, patients were randomized to receive twice a day doses of either 0.6 mg or 0.9 mg of SIGNIFOR given subcutaneously.
The mean age of patients was approximately 40 years old with a predominance of female patients (78%).
The majority of the patients had persistent or recurrent Cushing's disease (83%) and few patients (≤ 5%) in either treatment group had received previous pituitary irradiation.
The median exposure to the treatment was 10.4 months (0.03-37.8) with 68% of patients having at least 6-months exposure.
In the Phase III trial, adverse reactions were reported in 98% of patients.
The most common adverse reactions (frequency ≥ 20% in either group) were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes mellitus.
There were no deaths during the study.
5 WARNINGS AND PRECAUTIONS Hypocortisolism : Decreases in circulating levels of cortisol may occur resulting in biochemical and/or clinical hypocortisolism.
SIGNIFOR dose reduction or interruption and/or adding a low-dose short-term glucocorticoid may be necessary ( 5.1 ) Hyperglycemia and Diabetes (occurs with initiation) : Intensive glucose monitoring is recommended and may require initiation or adjustment of anti-diabetic treatment per standard of care ( 5.2 ) Bradycardia and QT Prolongation : Use with caution in at-risk patients;
ECG testing prior to dosing and on treatment ( 5.3 , 7.1 ) Liver Test Elevations : Evaluate liver tests prior to and during treatment ( 5.4 ) Cholelithiasis and Complications of Cholelithiasis : Monitor periodically.
Discontinue if complications of cholelithiasis are suspected ( 5.5 ) Steatorrhea and Malabsorption of Dietary Fats : New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur.
If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency ( 5.7 ) 5.1 Hypocortisolism Treatment with SIGNIFOR leads to suppression of adrenocorticotropic hormone (ACTH) secretion in Cushing's disease.
Like all medications, Signifor can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: