Applies to osilodrostat: oral tablet.
Serious side effects of Osilodrostat
Along with its needed effects, osilodrostat may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking osilodrostat:
More common
- Bladder pain
- bloody or cloudy urine
- blurred vision
- chills
- confusion
- cough
- darkening of the skin
- decreased urine
- diarrhea
- difficult, burning, or painful urination
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- dry mouth
- fast, pounding, or irregular heartbeat or pulse
- fever
- frequent urge to urinate
- general feeling of discomfort or illness
- headache
- increased thirst
- joint pain
- loss of appetite
- lower back or side pain
- mental depression
- mood changes
- muscle pain or cramps
- nausea
- nervousness
- numbness or tingling in the hands, feet, or lips
- pale skin
- pounding in the ears
- runny nose
- seizures
- shivering
- skin rash
- slow heartbeat
- sore throat
- sweating
- swelling of the arms or legs
- trouble sleeping
- troubled breathing with exertion
- unusual bleeding or bruising
- unusual tiredness or weakness
- vomiting
Less common
- Fainting
- irregular heartbeat, recurrent
Other side effects of Osilodrostat
Some side effects of osilodrostat may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
- Acne
- anxiety
- back pain
- decreased appetite
- depression
- difficulty in moving
- heartburn
- increased hair growth, especially on the face
- indigestion
- muscle stiffness
- stomach discomfort, upset, or pain
- stuffy nose
- thinning or loss of hair
For Healthcare Professionals
Applies to osilodrostat: oral tablet.
General
The most common side effects reported were adrenal insufficiency, fatigue, nausea, headache, vomiting, and edema. The most serious side effect was adrenal insufficiency.[Ref]
Cardiovascular
Very common (10% or more): Increased QTcF (corrected QT interval by Fridericia; up to 13%), hypotension (includes orthostatic hypotension, decreased blood pressure, decreased diastolic blood pressure, decreased systolic blood pressure; up to 11.7%), hypertension (up to 10.2%)
Common (1% to 10%): Tachycardia, ECG QT prolonged, QT prolongation
Frequency not reported: Clinically relevant ECG findings[Ref]
Adverse reactions of QT prolongation and clinically relevant ECG findings were reported; 4% of patients had an event of QT prolongation, 2% of patients had a QTcF increase of greater than 60 milliseconds (ms) from baseline, and 13% of patients had a new QTcF value of greater than 450 ms.[Ref]
Dermatologic
Hirsutism and acne were "very common" in female patients.[Ref]
Very common (10% or more): Rash (includes erythematous rash, generalized rash, maculopapular rash, papular rash; up to 15.3%)
Common (1% to 10%): Hirsutism, acne, alopecia[Ref]
Endocrine
Of the patients with adrenal insufficiency, one-third had low cortisol levels indicative of this event; most patients had normal cortisol levels suggesting a cortisol withdrawal syndrome.
Hypocortisolism was reported at a rate of 31% up to 12 weeks and 18% from weeks 12 to 26; most cases were managed by reducing the dose of this drug and/or adding low-dose, short-term glucocorticoid therapy.
Increased blood testosterone was "very common" in female patients.
CYP450 11B1 inhibition by this drug was associated with accumulation of adrenal steroid precursors and increased testosterone. The most common adrenal hormone precursor-related adverse reactions were hypertension (14%) and hypokalemia (17%); edema (7%) and elevated blood pressure (15%) were reported. All cases of hypokalemia responded to potassium supplementation and/or mineralocorticoid antagonist therapy. In male patients, testosterone levels generally increased but remained within normal limits; all patients were asymptomatic with no values above the upper limit of normal at last measure. In female patients, mean testosterone levels increased from high normal at baseline to above the upper limit of the normal range; the increases reversed when treatment was interrupted. Increased testosterone was associated with mild to moderate cases of hirsutism (12%) or acne (11%) in a subset of female patients.
ACTH values greater than 10-fold the upper limit of normal were observed in some Cushing's disease patients treated with this drug in clinical trials.[Ref]
Very common (10% or more): Adrenal insufficiency (includes glucocorticoid deficiency, acute adrenocortical insufficiency, steroid withdrawal syndrome, decreased urine free cortisol, decreased cortisol; up to 51%), accumulation of adrenal steroid precursors (up to 42%), hypocortisolism (up to 31%), increased blood corticotrophin (up to 13.9%), abnormal hormone level (up to 11.7%), increased blood testosterone (up to 10.9%)
Frequency not reported: Increased adrenocorticotropic hormone (ACTH)[Ref]
Gastrointestinal
Very common (10% or more): Gastrointestinal disorders (up to 69%), nausea (up to 42%), vomiting (up to 22%), diarrhea (up to 14.6%), abdominal pain (includes upper abdominal pain, abdominal discomfort; up to 13.1%)
Common (1% to 10%): Dyspepsia, gastroenteritis[Ref]
Gastrointestinal disorders (mainly nausea, vomiting, diarrhea, and abdominal pain) were reported in 69% of patients; in many cases, the episodes were of short duration ( 1 to 2 days) and the severity was mild to moderate.[Ref]
Genitourinary
Very common (10% or more): Urinary tract infection (up to 11.7%)[Ref]
Hematologic
Of the 137 patients from the 48-week study, 18 patients had at least 1 measured ANC below the normal limit and 2 patients had neutropenia. No concomitant infections and/or fever were reported in patients with decreased ANC.[Ref]
Very common (10% or more): Decreased absolute neutrophil count (ANC; up to 13%), anemia (up to 10.2%)
Common (1% to 10%): Neutropenia[Ref]
Hepatic
Liver enzyme elevations in patients treated with this drug were infrequent, typically mild, and reversed spontaneously or after dose adjustment. Most abnormal liver parameters occurred during dose-titration and no patients discontinued therapy due to abnormal liver chemistry parameters. Increased ALT or AST greater than 3 times the upper limit of normal was reported in 4% of patients during the 48-week study.[Ref]
Common (1% to 10%): Increased transaminases, increased ALT/AST
Frequency not reported: Elevated liver enzymes, abnormal liver parameters[Ref]
Metabolic
Very common (10% or more): Hypokalemia (includes decreased blood potassium; up to 12.4%), decreased appetite (up to 11.7%)[Ref]
Musculoskeletal
Very common (10% or more): Arthralgia (up to 17.5%), back pain (up to 15.3%), myalgia (up to 12.4%)[Ref]
Nervous system
Very common (10% or more): Headache (includes head discomfort; up to 34%), dizziness (includes postural dizziness; up to 13.9%)
Common (1% to 10%): Syncope[Ref]
Oncologic
Very common (10% or more): Changes in pituitary corticotroph tumor volume[Ref]
Increased pituitary corticotroph tumor volume greater than 20% from baseline was reported in 21/137 (15%) patients, while decreased tumor volume greater than 20% from baseline was reported in 24/137 (18%) patients at week 48. There was no correlation between tumor volume increase and increased ACTH. There was no specific pattern of timing of the tumor volume increase and no relationship with the total and last dose of this drug used in the study.[Ref]
Other
Very common (10% or more): Fatigue (includes lethargy, asthenia; up to 44%), edema (includes peripheral edema, generalized edema, localized edema; up to 21.2%), pyrexia (up to 10.9%)
Common (1% to 10%): Malaise[Ref]
Psychiatric
Common (1% to 10%): Insomnia, anxiety, depression[Ref]
Respiratory
Very common (10% or more): Nasopharyngitis (up to 19.7%), cough (up to 10.2%)[Ref]
