SIGNIFOR

Agents for Cushing's Syndrome
Somatostatin and analogs

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intramuscular Administration

Pasireotide Injection Suspension (e.g., Signifor LAR)
For intramuscular (IM) administration only into the right or left gluteus. Never administer intravenously.
Pasireotide suspension must be reconstituted and administered by a trained health care professional only.
An instruction booklet for preparation of the IM drug suspension is provided in each kit.
Use the provided diluent only.
Preparation: Not following the proper reconstitution steps could result in failure to deliver the drug appropriately.
Drug product kit should remain at room temperature for a minimum of 30 minutes before reconstitution, but do not exceed 24 hours.
After adding the 2 mL of the provided diluent solution, shake the vial moderately in a horizontal direction for a minimum of 30 seconds until uniform suspension is formed.
After reconstitution of the 10 mg vial the final concentration will be 5 mg/mL.
After reconstitution of the 20 mg vial the final concentration will be 10 mg/mL.
After reconstitution of the 30 mg vial the final concentration will be 15 mg/mL.
After reconstitution of the 40 mg vial the final concentration will be 20 mg/mL.
After reconstitution of the 60 mg vial the final concentration will be 30 mg/mL.
Administer the drug suspension immediately after preparation. Administer the dose for the patient in its entirety.
If you have questions about preparation and/or administration of Pasireotide suspension, call 1-888-NOW-NOVA or 1-888-669-6682.

Subcutaneous Administration

Pasireotide Injection Solution (e.g., Signifor)
Pasireotide is administered by subcutaneous injection. The patient may be taught to self-administer the medicine if determined to be appropriate by the prescriber; see patient insert from the manufacturer.
The injection solution should be clear and colorless; do not use an ampule that appears cracked, damaged, or cloudy.
Tap the top of the ampule to get any liquid at the top to move to the bottom.
To open the ampule, pull the top sideways until the top snaps off at the line marked on the ampule's neck.
Using the long needle, withdraw all of the liquid without the needle touching the outside of the ampule. Replace the long needle with the short needle, and tap the syringe to get any air bubbles to rise.
Push up on the plunger gently until a drop of liquid appears.
Chose an injection site on the top of the thigh or abdomen that does NOT show signs of inflammation or irritation. Use of the same injection site for 2 consecutive injections is not recommended. Also, avoid multiple injections at or near the same site within short periods of time.
Gently pinch the skin, and insert the needle at a 45-degree angle using a quick, dart-like motion. Keeping the skin pinched, gently press the plunger to deliver all the medicine.
Slowly let go of the skin and remove the needle.
Place a cotton ball or gauze pad over the site and press for about 5 seconds. Do not massage the site.
Do not reuse unused portions of the ampules and properly dispose of the ampules after use.

Severe

bradycardia / Rapid / 5.0-10.0
AV block / Early / 6.0-6.0
asthenia / Delayed / 2.0-2.0
pancreatitis / Delayed / 0-1.0
myalgia / Early / 1.0-1.0
diabetic ketoacidosis / Delayed / Incidence not known

Moderate

cholelithiasis / Delayed / 10.0-33.0
hypertension / Early / 8.0-15.0
peripheral edema / Delayed / 10.0-14.0
hypercholesterolemia / Delayed / 6.0-10.0
constipation / Delayed / 5.0-9.0
elevated hepatic enzymes / Delayed / 1.0-8.0
hyperuricemia / Delayed / 7.0-7.0
hypotension / Rapid / 7.0-7.0
QT prolongation / Rapid / 4.0-6.0
hypokalemia / Delayed / 6.0-6.0
adrenocortical insufficiency / Delayed / 2.0-6.0
anemia / Delayed / 3.0-6.0
hyperamylasemia / Delayed / 2.0-2.0
jaundice / Delayed / 0-1.0
hyperbilirubinemia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hypopituitarism / Delayed / Incidence not known
hypothyroidism / Delayed / Incidence not known
hematoma / Early / Incidence not known

Mild

headache / Early / 24.0-26.0
fatigue / Early / 10.0-24.0
abdominal pain / Early / 2.0-23.0
alopecia / Delayed / 2.0-18.0
injection site reaction / Rapid / 2.0-17.0
pharyngitis / Delayed / 6.0-16.0
insomnia / Early / 4.0-14.0
weakness / Early / 11.0-11.0
anxiety / Delayed / 6.0-11.0
anorexia / Delayed / 10.0-10.0
vomiting / Early / 4.0-10.0
dizziness / Early / 2.0-10.0
arthralgia / Delayed / 8.0-10.0
pruritus / Delayed / 8.0-8.0
back pain / Delayed / 6.0-8.0
influenza / Delayed / 8.0-8.0
infection / Delayed / 7.0-7.0
vertigo / Early / 6.0-6.0
weight loss / Delayed / 0-5.0
flatulence / Early / 5.0-5.0
cough / Delayed / 5.0-5.0

Signifor, Signifor LAR

Rx

Somatostatin analog; inhibits ACTH secretion and, thus, decreases cortisol secretion
Used for adults with Cushing’s disease or acromegaly for whom pituitary surgery is not an option or has not been curative
Long-acting injection is administered IM once every 4 weeks; immediate release injection is given subcutaneously twice daily

For the treatment of Cushing's syndrome in patients for whom pituitary surgery is not an option or has not been curative.
Pasireotide has been granted orphan drug status by the FDA for this indication.
Subcutaneous dosage Adults

Initially, 0.6 mg to 0.9 mg subcutaneously twice daily; titrate dose in 0.3-mg increments based on response and tolerability within the recommended range of 0.3 mg to 0.9 mg subcutaneously twice daily. Response is defined as a clinically meaningful reduction in 24-hour urinary free cortisol concentrations and/or disease sign and/or symptom improvement. The maximum urinary free cortisol reduction is usually seen by month 2 of pasireotide receipt.

Intramuscular dosage (Signifor LAR) Adults

10 mg IM once every 4 weeks (every 28 days) initially. May increase in patients who have not normalized 24-hour urinary free cortisol (UFC) after 4 months of treatment with the 10 mg/month dose and who tolerate this dose. Max: 40 mg IM once every 28 days. Dose reduction, dose interruption, or drug discontinuation may be required in patients experiencing adverse reactions or who over-respond to treatment (e.g., cortisol levels less than the lower limit of normal or in the low part of the normal range with symptoms suggestive of adrenal insufficiency). If a patient is receiving 10 mg once every 28 days, the dose may be either interrupted or discontinued. In a phase 3, year-long double-blind randomized clinical trial in 150 patients with persistent, recurrent, or newly diagnosed Cushing's disease, this drug regimen was effective; the primary endpoint of attaining a mean UFC within normal limits at month 7, regardless of dose titration at month 4, was met by more than 40% of patients. Clinical benefits, as measured by objective improvements in the signs and symptoms of disease, were observed at month 7 and continued through the end of the trial.

For the treatment of acromegaly in patients who have had an inadequate response to surgery and/or for whom surgery is not an option.
Pasireotide has been designated an orphan drug by the FDA for this indication.
Intramuscular dosage (Signifor LAR) Adults

Initiate therapy at 40 mg IM once every 4 weeks (every 28 days). The dose may be increased to a maximum of 60 mg for patients who have not normalized growth hormone (GH) and/or age and sex adjusted insulin-like growth factor-1 (IGF-1) levels after 3 months of treatment with long-acting pasireotide at 40 mg and who tolerate this dose. In patients experiencing adverse reactions or who over respond to treatment (age and sex adjusted IGF-1 less than the lower limit of normal), dose reduction may be required. The dose may be decreased, either temporarily or permanently, by 20-mg decrements.

For the prevention of postoperative pancreatic fistula†, leak, or abscess in patients undergoing pancreaticoduodenectomy or distal pancreatectomy. Subcutaneous dosage Adults

900 mcg subcutaneously twice daily beginning the morning of surgery and continuing for 7 days.

†Indicates off-label use

Hepatic Impairment

Mild impairment (Child-Pugh class A): No dose adjustment needed.
Moderate impairment (Child-Pugh class B): For immediate-release injection (Signifor): Initially 0.3 mg subcutaneously twice daily; Max: 0.6 mg subcutaneously twice daily. For the long-acting injection (Signifor LAR): For acromegaly, give 20 mg IM every 4 weeks initially; Max: 40 mg IM every 4 weeks. For Cushing's disease, give 10 mg IM every 4 weeks initially; Max: 20 mg IM every 4 weeks.
Severe impairment (Child-Pugh class C): Avoid use.

Renal Impairment

No dosage adjustments are needed.

Acarbose: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Acebutolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Adagrasib: (Major) Concomitant use of adagrasib and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfuzosin: (Moderate) Use caution when administering alfuzosin with pasireotide due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Alogliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Alogliptin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Amiodarone: (Major) Concomitant use of pasireotide and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with pasireotide. Amisulpride causes dose- and concentration- dependent QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and clarithromycin is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include pasireotide.
Antidiabetic Agents: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Apomorphine: (Moderate) Use apomorphine and pasireotide together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Arsenic Trioxide: (Major) Cautious use of pasireotide and arsenic trioxide is needed, as coadministration may have additive effects on the prolongation of the QT interval. If possible, drugs that are known to prolong the QT interval, such as pasireotide, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Major) Coadministration of artemether; lumefantrine and pasireotide may have additive effects on the prolongation of the QT interval. The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if pasireotide must be used with or after artemether; lumefantrine treatment.
Asenapine: (Major) Coadministration of asenapine and pasireotide may have additive effects on the prolongation of the QT interval. Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
Atenolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Atenolol; Chlorthalidone: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary. (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azilsartan; Chlorthalidone: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Azithromycin: (Major) Concomitant use of pasireotide and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Cautious use of pasireotide and bedaquiline is needed, as coadministration may have additive effects on the prolongation of the QT interval. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Beta-adrenergic blockers: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Betaxolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bisoprolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary. (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Brimonidine; Timolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Bromocriptine: (Moderate) Monitor blood glucose levels regularly in patients taking bromocriptine for diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Bumetanide: (Moderate) Cautious use of pasireotide and loop diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Buprenorphine: (Major) Concomitant use of pasireotide and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of pasireotide and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cabotegravir; Rilpivirine: (Moderate) Use caution when using pasireotide in combination with rilpivirine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Calcium-channel blockers: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as calcium-channel blockers. Dose adjustments of calcium-channel blockers may be necessary.
Canagliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Carteolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Carvedilol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Ceritinib: (Major) Avoid coadministration of ceritinib with pasireotide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Pasireotide is also associated with QT prolongation; coadministration may have additive effects.
Chloroquine: (Major) Avoid coadministration of chloroquine with pasireotide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Chlorothiazide: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Chlorpromazine: (Major) Cautious use of pasireotide and chlorpromazine is needed, as coadministration may have additive effects on the prolongation of the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
Chlorpropamide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Chlorthalidone: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Chlorthalidone; Clonidine: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of pasireotide and cisapride is contraindicated. QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Coadministration of pasireotide and drugs that prolong the QT interval may have additive effects on the prolongation of the QT interval.
Citalopram: (Major) Concomitant use of pasireotide and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and clarithromycin is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Clofazimine: (Moderate) Concomitant use of clofazimine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clozapine: (Moderate) Use caution when using pasireotide in combination with clozapine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of promethazine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Codeine; Promethazine: (Moderate) Concomitant use of promethazine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Crizotinib: (Major) Avoid coadministration of crizotinib with pasireotide due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Cyclosporine: (Major) Pasireotide and cyclosporine coadministration may decrease the relative bioavailability of cyclosporine. Patients taking both of these drugs should have their cyclosporine concentrations monitored; if needed, adjust the cyclosporine dosage to maintain therapeutic concentrations.
Dapagliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Dasatinib: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and pasireotide. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Desflurane: (Major) Cautious use of pasireotide and drugs that prolong the QT interval, such as halogenated anesthetics, is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Deutetrabenazine: (Moderate) Use caution when using pasireotide in combination with other drugs that prolong the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supratherapeutic doses. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Quinidine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Disopyramide: (Major) Cautious use of pasireotide and disopyramide is needed, as coadministration may have additive effects on the prolongation of the QT interval. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
Dofetilide: (Major) Coadministration of dofetilide and pasireotide is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with pasireotide as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Use caution when using pasireotide in combination with rilpivirine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with pasireotide as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with pasireotide as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Dorzolamide; Timolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Dronedarone: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of pasireotide and dronedarone is contraindicated. Coadministration of pasireotide and drugs that prolong the QT interval may have additive effects on the prolongation of the QT interval. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce TdP and is contraindicated.
Droperidol: (Major) Coadministration of droperidol and pasireotide may have additive effects on the prolongation of the QT interval. Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
Dulaglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with pasireotide as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with pasireotide as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with pasireotide as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Eliglustat: (Moderate) Use caution when using pasireotide in combination with eliglustat as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Empagliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Use caution when using pasireotide in combination with rilpivirine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Use caution when using pasireotide in combination with rilpivirine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Encorafenib: (Major) Avoid coadministration of encorafenib and pasireotide due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Entrectinib: (Major) Avoid coadministration of entrectinib with pasireotide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and pasireotide must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Coadministration may have additive effects on the prolongation of the QT interval.
Ertugliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Erythromycin: (Major) Concomitant use of pasireotide and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Moderate) Concomitant use of escitalopram and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Esmolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Ethacrynic Acid: (Moderate) Cautious use of pasireotide and loop diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Exenatide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Fingolimod: (Moderate) Use caution when using pasireotide in combination with fingolimod as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of pasireotide and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Moderate) Concomitant use of fluconazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Minor) Use caution when using pasireotide in combination with fluphenazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Fluphenazine is associated with a possible risk for QT prolongation.
Fluvoxamine: (Moderate) Use caution when using pasireotide in combination with fluvoxamine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. QT prolongation and torsade de pointes (TdP) has been reported during fluvoxamine post-marketing use.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as pasireotide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Pasireotide may also prolong the QT interval. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Fostemsavir: (Moderate) Use caution when using pasireotide with fostemsavir due to the potential for QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Furosemide: (Moderate) Cautious use of pasireotide and loop diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Gallium Ga 68 Dotatate: (Moderate) Image patients with gallium Ga 68 dotatate just prior to dosing with non-radioactive, long-acting somatostatin analogs. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with gallium Ga 68 dotatate. These drugs may competitively bind to the same somatostatin receptors.
Gemifloxacin: (Moderate) Use caution when using pasireotide in combination with gemifloxacin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and pasireotide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and pasireotide is necessary. Gilteritinib has been associated with QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Glasdegib: (Major) Avoid coadministration of glasdegib with pasireotide due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Glimepiride: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Glipizide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Glipizide; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Glyburide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Glyburide; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
Granisetron: (Moderate) Use granisetron with caution in combination with pasireotide due to increased risk for QT prolongation. Granisetron has been associated with QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Granisetron has been associated with QT prolongation.
Halogenated Anesthetics: (Major) Cautious use of pasireotide and drugs that prolong the QT interval, such as halogenated anesthetics, is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Haloperidol: (Moderate) Use caution when using pasireotide in combination with haloperidol as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Hydroxychloroquine: (Major) Concomitant use of pasireotide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibutilide: (Major) Cautious use of pasireotide and ibutilide is needed, as coadministration may have additive effects on the prolongation of the QT interval. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as pasireotide.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with pasireotide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Insulin Aspart: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Detemir: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Glargine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Glulisine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Insulin, Inhaled: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Isoflurane: (Major) Cautious use of pasireotide and drugs that prolong the QT interval, such as halogenated anesthetics, is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Itraconazole: (Moderate) Use caution when using pasireotide in combination with itraconazole as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Itraconazole has been associated with prolongation of the QT interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with pasireotide due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and pasireotide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Labetalol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and clarithromycin is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with pasireotide. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Lefamulin: (Major) Avoid coadministration of lefamulin with pasireotide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with pasireotide due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occu

rred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
Levobunolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and pasireotide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Linagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Linagliptin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Liraglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Lithium: (Moderate) Concomitant use of lithium and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lixisenatide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with pasireotide due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Loop diuretics: (Moderate) Cautious use of pasireotide and loop diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Loperamide: (Moderate) Use caution when using pasireotide in combination with loperamide as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Loperamide; Simethicone: (Moderate) Use caution when using pasireotide in combination with loperamide as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with pasireotide due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supratherapeutic doses.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as pasireotide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Maprotiline: (Moderate) Use caution when using pasireotide in combination with maprotiline as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Moderate) Use caution when using pasireotide in combination with mefloquine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Metformin; Repaglinide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Metformin; Rosiglitazone: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Methadone: (Major) The need to coadminister methadone with pasireotide should be done with extreme caution and a careful assessment of treatment risks versus benefits, as coadministration may have additive effects on the prolongation of the QT interval. At high doses, methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses averaging approximately 400 mg/day.
Methyclothiazide: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Metolazone: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Metoprolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary. (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Metronidazole: (Moderate) Concomitant use of metronidazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) The concomitant use of midostaurin and pasireotide may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram (ECG) monitoring. Obtain a baseline ECG prior to starting pasireotide and perform serum electrolyte monitoring; patients receiving long-acting pasireotide who are at risk for QT prolongation should also be monitored for an effect on the QT interval at the time of maximum drug concentration (21 days after injection). In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin and in patients who received pasireotide.
Mifepristone: (Major) Concomitant use of pasireotide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Miglitol: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mobocertinib: (Major) Concomitant use of mobocertinib and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval, such as pasireotide, as coadministration may have additive effects on the prolongation of the QT interval. Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
Nadolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Nateglinide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Nebivolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Nebivolol; Valsartan: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and pasireotide; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. QT prolongation has occurred with therapeutic and subtherapeutic doses of pasireotide.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Use caution when using pasireotide in combination with olanzapine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of fluoxetine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Use caution when using pasireotide in combination with olanzapine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Moderate) Use caution when using pasireotide in combination with olanzapine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Ondansetron: (Major) Concomitant use of pasireotide and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with pasireotide as concurrent use may increase the risk of QT prolongation. Osilodrostat is associated with dose-dependent QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Osimertinib: (Major) Avoid coadministration of pasireotide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation has also occurred with pasireotide at therapeutic and supra-therapeutic doses.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of pasireotide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking pasireotide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pacritinib: (Major) Concomitant use of pacritinib and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as pasireotide. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. If coadministration is necessary, closely monitor patients with known risk factors for cardiac disease or arrhythmias.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include pasireotide.
Pazopanib: (Major) Coadministration of pazopanib and pasireotide is not advised, as coadministration may have additive effects on the prolongation of the QT interval. If pazopanib and pasireotide must be continued, closely monitor the patient for QT interval prolongation.
Pentamidine: (Major) Cautious use of pasireotide and pentamidine is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Perphenazine: (Minor) Use caution when using pasireotide in combination with perphenazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Perphenazine is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Use caution when using pasireotide in combination with perphenazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Perphenazine is associated with a possible risk for QT prolongation.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as pasireotide. Coadministration may increase the risk for QT prolongation.
Pimozide: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of pasireotide and pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Coadministration of pasireotide and drugs that prolong the QT interval may have additive effects on the prolongation of the QT interval.
Pindolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Pioglitazone: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Pitolisant: (Major) Avoid coadministration of pitolisant with pasireotide as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking pasireotide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Posaconazole: (Moderate) Use caution when using pasireotide in combination with posaconazole as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Pramlintide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Primaquine: (Moderate) Use caution when using pasireotide in combination with primaquine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Primaquine is associated with QT prolongation.
Procainamide: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and pasireotide is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Prochlorperazine: (Minor) Use caution when using pasireotide in combination with prochlorperazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Prochlorperazine is associated with a possible risk for QT prolongation.
Promethazine: (Moderate) Concomitant use of promethazine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Concomitant use of propafenone and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propranolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary. (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Quetiapine: (Major) Concomitant use of quetiapine and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Quinidine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Quinine: (Major) Concurrent use of quinine and pasireotide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pasireotide may have additive effects on the prolongation of the QT interval.
Quizartinib: (Major) Concomitant use of quizartinib and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Moderate) Use caution when using pasireotide in combination with ranolazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Regular Insulin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Relugolix: (Moderate) Use caution when using pasireotide in combination with other drugs that prolong the QT interval such as relugolix. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Use caution when using pasireotide in combination with other drugs that prolong the QT interval such as relugolix. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Repaglinide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Ribociclib: (Major) Avoid coadministration of ribociclib with pasireotide due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Pasireotide has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with pasireotide due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Pasireotide has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
Rilpivirine: (Moderate) Use caution when using pasireotide in combination with rilpivirine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Risperidone: (Moderate) Use risperidone and pasireotide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with pasireotide as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Rosiglitazone: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Saquinavir: (Major) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as pasireotide. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
Saxagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with pasireotide is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Semaglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Sertraline: (Moderate) Concomitant use of sertraline and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Cautious use of pasireotide and drugs that prolong the QT interval, such as halogenated anesthetics, is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving pasireotide due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Sitagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Use caution when using pasireotide in combination with solifenacin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with pasireotide due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. In addition, pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with pasireotide. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Sunitinib can prolong the QT interval.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with pasireotide. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telavancin: (Moderate) Use caution when using pasireotide in combination with telavancin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Telavancin has been associated with QT prolongation.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc) and should be used cautiously and with close monitoring with pasireotide as coadministration may have additive effects on the prolongation of the QT interval.
Thiazide diuretics: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Thioridazine: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of pasireotide and thioridazine is contraindicated. Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval. Coadministration of pasireotide and drugs that prolong the QT interval may have additive effects on the prolongation of the QT interval.
Timolol: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Tolazamide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Tolbutamide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Tolterodine: (Moderate) Use caution when using pasireotide in combination with tolterodine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of pasireotide with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Prolongation of the QT interval has also occurred with pasireotide therapy at therapeutic and supra-therapeutic doses.
Torsemide: (Moderate) Cautious use of pasireotide and loop diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Trazodone: (Major) Concomitant use of trazodone and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Use caution when using pasireotide in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Vandetanib: (Major) Avoid coadministration of vandetanib with pasireotide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval has also occurred with pasireotide at therapeutic and supra-therapeutic doses.
Vardenafil: (Moderate) Concomitant use of vardenafil and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and pasireotide must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation as coadministration may have additive effects on the prolongation of the QT interval.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Voclosporin: (Moderate) Concomitant use of voclosporin and pasireotide may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and clarithromycin is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Voriconazole: (Moderate) Use caution when using pasireotide in combination with voriconazole as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Voriconazole has been associated with QT prolongation and rare cases of torsades de pointes.
Vorinostat: (Moderate) Use caution when using pasireotide in combination with vorinostat as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Vorinostat therapy is associated with a risk of QT prolongation.
Ziprasidone: (Major) Concomitant use of ziprasidone and pasireotide should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.

Pasireotide Intramuscular Inj Pwd F/Susp: 10mg, 20mg, 30mg, 40mg, 60mg
Pasireotide/Signifor Subcutaneous Inj Sol: 0.3mg, 0.6mg, 0.9mg, 1mL

Adults

1.8 mg/day subcutaneously for regular-release injection (Signifor). For long acting injection (Signifor LAR): 40 mg IM every 4 weeks IM for Cushing's disease and 60 mg IM every 4 weeks for acromegaly.

Geriatric

1.8 mg/day subcutaneously for regular-release injection (Signifor). For long acting injection (Signifor LAR): 40 mg IM every 4 weeks IM for Cushing's disease and 60 mg IM every 4 weeks for acromegaly.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Pasireotide is a somatostatin analogue that binds and, thus, activates somatostatin receptors. Of the 5 human somatostatin (hsst) receptors, pasireotide has the greatest binding affinity for hsst5 but also binds with high affinity to hsst1, hsst2, and hsst3. As a comparison, the binding affinity for somatostatin is greatest for hsst2, although somatostatin binds with high affinity to each of the 5 receptor subtypes.
 
Corticotroph adenomas express somatostatin receptors, predominantly hsst5. Activation of hsst5 inhibits corticotropin secretion, which lowers cortisol secretion, helping to normalize mean urinary free cortisol levels. In addition to corticotropin secretion inhibition, pasireotide also may inhibit other pituitary hormones such as growth hormone because the pharmacological activity of pasireotide mimics that of somatostatin. After a single 0.6 mg subcutaneous dose to healthy adults, the median change from baseline in systemic exposure of growth hormone over 2 hours was -82.5% (range, -59.6 to -96.5%). Patients received a growth hormone-releasing hormone (GHRH) stimulation test of 1 mcg/kg approximately 3 hours after pasireotide administration, and plasma growth hormone concentrations were obtained at designated time points up to 2 hours after GHRH administration.
 
In healthy patients, pasireotide-induced hyperglycemia appears to be mediated by a severe defect in the secretion of insulin and the incretin hormones GLP-1 and gastric inhibitory peptide. Glucagon secretion appears moderately inhibited. In contrast, peripheral and hepatic insulin sensitivity appear to be unaffected.

Pasireotide is administered parenterally; the regular-release formulation should be given subcutaneously, while the long-acting formulation should only be given intramuscularly. Systemic exposure is dose-proportional after single and multiple doses. It is 88% bound to plasma proteins, and binding is independent of concentration. In healthy volunteers, unchanged pasireotide is the predominant form found in plasma, urine, and feces. Elimination is mainly by biliary excretion. Of a radioactive dose, 55.9 +/- 6.63% was recovered over the first 10 days; 48.3 +/- 8.16 in feces and 7.63 +/- 2.03% in urine. The half-life of the subcutaneous injection solution was calculated to be approximately 12 hours. In healthy volunteers, the apparent clearance (CL/F) of the intramuscular long-acting pasireotide suspension is on average 4.5 to 8.5 L/hour.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: P-glycoprotein (P-gp)
Pasireotide is likely to be a substrate of P-gp, but the impact of P-gp on pharmacokinetic parameters is expected to be low. Pasireotide is not a substrate of efflux transporter BCRP, influx transporter OCT1, or influx transporters OATP 1B1, 1B3, or 2B1. Suppression of growth hormone secretion by somatostatin analogs such as pasireotide may decrease the metabolic clearance of drugs metabolized by CYP450 enzymes.

Intramuscular Route

Steady state for long-acting pasireotide injection is achieved after 3 months. Following multiple IM doses every 4 weeks (every 28 days), long-acting pasireotide demonstrates approximately dose-proportional pharmacokinetic exposures in the dose range of 20 mg to 60 mg every 4 weeks in patients with acromegaly.

Subcutaneous Route

The peak plasma concentration (Cmax) of pasireotide subcutaneous injection is attained within 0.25 to 0.5 hours after administration in healthy patients and is dose-proportional.

Pregnancy

The limited data with pasireotide in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage during pregnancy; however, animal studies show evidence of fetal harm. Increased implantation loss and decreased viable fetuses, corpora lutea, and implantation sites were noted in rats exposed to less than the human clinical exposure based on body surface area comparisons across species. An effect on fertility in humans is not clear. At 5-fold higher than the maximum therapeutic exposure in humans, abnormal cycles or acyclicity was noted in the rats which were exposed to pasireotide before mating and after conception. Premenopausal females may be at risk for unintended pregnancy as the therapeutic benefits of a reduction or normalization of serum cortisol levels in female patients with Cushing's disease treated with pasireotide may lead to improved fertility.

There is no information available regarding the presence of pasireotide in human milk, the effects of the drug on the breast-fed infant, or the effects of the drug on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.