Slideshows Images Quizzes

Copyright © 2018 by RxList Inc. RxList does not provide medical advice, diagnosis or treatment. See additional information.

Isturisa

Last reviewed on RxList: 10/13/2020
Isturisa Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Isturisa?

Isturisa (osilodrostat) is a cortisol synthesis inhibitor used to treat adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative.

What Are Side Effects of Isturisa?

Side effects of Isturisa include:

Dosage for Isturisa

The starting dose of Isturisa is 2 mg orally twice daily, with or without food. The dosage is adjusted by 1 to 2 mg twice daily, no more frequently than every 2 weeks based on rate of cortisol changes, individual tolerability and improvement in signs and symptoms. The maximum recommended dosage of Isturisa is 30 mg twice daily.

Isturisa In Children

The safety and effectiveness of Isturisa in pediatric patients have not been established.

What Drugs, Substances, or Supplements Interact with Isturisa?

Isturisa may interact with other medicines such as:

  • strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin),
  • strong CYP3A4 and/or CYP2B6 inducers (e.g., carbamazepine, rifampin, phenobarbital), and
  • CYP1A2 and CYP2C19 substrates with a narrow therapeutic index (such as theophylline, tizanidine, and S-mephenytoin).

Tell your doctor all medications and supplements you use.

Isturisa During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Isturisa; it is unknown how it would affect a fetus. It is unknown if Isturisa passes into breast milk. Because of the potential for serious adverse reactions (such as adrenal insufficiency) in breastfed infants, breastfeeding is not recommended during treatment with Isturisa and for at least one week after treatment.

Additional Information

Our Isturisa (osilodrostat) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Isturisa Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
  • swelling in your feet or ankles, feeling short of breath;
  • decreased adrenal gland hormones--nausea, vomiting, stomach pain, loss of appetite, feeling tired or light-headed, muscle or joint pain, skin discoloration, craving salty foods;
  • increased adrenal gland hormones--hunger, weight gain, swelling, skin discoloration, slow wound healing, sweating, acne, increased body hair, tiredness, mood changes, muscle weakness, missed menstrual periods, sexual changes; or
  • low potassium level--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

  • nausea;
  • feeling tired;
  • headache; or
  • swelling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Isturisa (Osilodrostat Tablets, for Oral Use)

Isturisa Professional Information

SIDE EFFECTS

Clinically significant adverse reactions that appear in other sections of the labeling include:

  • Hypocortisolism [see WARNINGS AND PRECAUTIONS]
  • QT Prolongation [see WARNINGS AND PRECAUTIONS]
  • Elevations in Adrenal Hormone Precursors and Androgens [see WARNINGS AND PRECAUTIONS]

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 clinical trials of another drug and may not reflect the rates observed in practice.

A total of 137 Cushing's disease patients were exposed to ISTURISA in the study [see Clinical Studies]. The adverse reactions that occurred with frequency higher than 10% during the core 48-week period are shown in Table 1.

Table 1: Adverse Reactions With a Frequency of More Than 10% in 48-week Clinical Study in Cushing's Disease Patients

Adverse Reaction Type(N = 137) %
Adrenal insufficiencya43.1
Fatigueb38.7
Nausea37.2
Headachec30.7
Edemad21.2
Nasopharyngitis19.7
Vomiting19
Arthralgia17.5
Back pain15.3
Rashe15.3
Diarrhea14.6
Blood corticotrophin increased13.9
Dizzinessf13.9
Abdominal paing13.1
Hypokalaemiah12.4
Myalgia12.4
Decreased appetite11.7
Hormone level abnormal11.7
Hypotensioni11.7
Urinary tract infection11.7
Blood testosterone increased10.9
Pyrexia10.9
Anemia10.2
Cough10.2
Hypertension10.2
Influenza10.2
a Adrenal insufficiency includes glucocorticoid deficiency, adrenocortical insufficiency acute, steroid withdrawal syndrome, cortisol free urine decreased, cortisol decreased. One-third of the subjects with this event had low cortisol levels indicative of Adrenal Insufficiency. The majority of subjects had normal cortisol levels suggesting a cortisol withdrawal syndrome.
b Fatigue includes lethargy, asthenia.
c Headache includes head discomfort.
d Edema includes edema peripheral, generalized edema, localized edema.
e Rash includes rash erythematous, rash generalized, rash maculopapular, rash papular.
f Dizziness includes dizziness postural.
g Abdominal pain includes abdominal pain upper, abdominal discomfort
h Hypokalaemia includes blood potassium decreased.
i Hypotension includes orthostatic hypotension, blood pressure decreased, blood pressure diastolic decreased, blood pressure systolic decreased.

Other notable adverse reactions which occurred with a frequency less than 10% were: hirsutism (9.5%), acne (8.8%), dyspepsia (8%), insomnia (8%), anxiety (7.3%), depression (7.3%), gastroenteritis (7.3%), malaise (6.6%), tachycardia (6.6%), alopecia (5.8%), transaminases increased (4.4%), electrocardiogram QT prolongation (3.6%), and syncope (1.5%).

Description Of Selected Adverse Reactions

Gastrointestinal Disorders

Gastrointestinal disorders, predominantly nausea, vomiting, diarrhea and abdominal pain were reported in 69% of patients. In many cases, the episodes were of short duration (1-2 days) and the severity was mild to moderate.

Hypocortisolism

Hypocortisolism was reported at a rate of 31% up to 12 weeks, and 18% from Weeks 12 to 26. The majority of cases were manageable by reducing the dose of ISTURISA and/or adding low-dose, short-term glucocorticoid therapy.

Changes In Pituitary Tumor Volume

An increase in the pituitary corticotroph tumor volume by greater than 20% from baseline was observed in 21/137 (15%) patients, while a decrease in tumor volume by greater than 20% from baseline was observed in 24/137 (18%) patients at Week 48. Eight patients discontinued because of an increase in tumor volume. There was no correlation between tumor volume increase and increase in adrenocorticotrophic hormone (ACTH). There was no specific pattern of timing of the tumor volume increase and no relationship with the total and the last dose of ISTURISA used in the study.

QTc Interval Prolongation

Adverse reactions of QT prolongation and clinically relevant ECG findings were reported. Five (4%) patients had an event of QT prolongation, 3 (2%) patients had a QTcF increase of > 60ms from baseline, and 18 (13%) had a new QTcF value of > 450ms [see CLINICAL PHARMACOLOGY].

Accumulation Of Adrenal Hormone Precursors

CYP11B1 inhibition by ISTURISA is associated with adrenal steroid precursor accumulation and testosterone increases [see WARNINGS AND PRECAUTIONS]. The incidence of adverse reactions potentially related to accumulation of adrenal hormone precursors was 42%. Hypertension and hypokalemia were the most common adrenal hormone precursor-related adverse reactions and occurred in 14% of patients and 17% of patients, respectively; edema was reported in 7% of patients, elevated blood pressure in 15% of patients. All cases of hypokalemia responded to treatment with potassium supplementation and/or mineralocorticoid antagonist therapy (e.g., spironolactone). One patient discontinued the study because of hypokalemia. In male patients testosterone levels generally increased but remained within normal limits; all patients were asymtomatic with no values above upper limit of normal (ULN) at last available value. In female patients, mean testosterone levels increased above the normal range from baseline and reversed when treatment was interrupted. The testosterone increase was associated with mild to moderate cases of hirsutism (12%) or acne (11%) in a subset of female patients.

Other Abnormal Laboratory Findings

Decreased Absolute Neutrophil Count

Of the 137 patients from the 48-week study, 18 patients had at least one measured absolute neutrophil count below the normal limit, 2 patients had an adverse reaction of neutropenia. No concomitant infections and/or fever were reported in patients with decreased absolute neutrophil count.

Elevated Liver Function Tests

Liver enzyme elevations in patients treated with ISTURISA were infrequent, typically mild and reversed spontaneously or following dose adjustment. Most liver abnormal parameters occurred during the dose-titration period and no patients discontinued ISTURISA drug due to abnormal liver chemistry parameters. Five (4%) patients had ALT or AST > 3 x ULN during the 48-week clinical study.

Read the entire FDA prescribing information for Isturisa (Osilodrostat Tablets, for Oral Use)

Related Resources for Isturisa

© Isturisa Patient Information is supplied by Cerner Multum, Inc. and Isturisa Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Health Solutions From Our Sponsors