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PASIREOTIDE


DIR Classification


Classification:Moderate-DIQT concern
Severity Score:3.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

  • WARNINGS AND PRECAUTIONS
  • Bradycardia and QT Prolongation
  • QT Prolongation
  • In cardiac electrophysiology studies (i.e., thorough QT studies) with pasireotide via subcutaneous route, QT prolongation occurred at therapeutic and supra-therapeutic doses [see Clinical Pharmacology (12.2)].
  • In the clinical studies, a corrected QT interval (i.e., QTcF) of greater than 480 ms was reported in 6 patients and an increase in the QTcF from baseline of greater than 60 ms was reported for seven patients on SIGNIFOR LAR. No patient on SIGNIFOR LAR had a QTcF value of greater than 500 ms [see Adverse Reactions (6.1), Clinical Pharmacology (12.2)].
  • SIGNIFOR LAR should be used with caution in patients who are at significant risk of developing prolongation of the QT interval, such as those listed below:
  • with congenital long QT prolongation
  • with uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina or clinically significant bradycardia
  • on anti-arrhythmic therapy or other substances that are known to lead to QT prolongation
  • with hypokalemia and/or hypomagnesemia
  • A baseline ECG is recommended prior to initiating therapy with SIGNIFOR LAR. Monitoring for an effect on the QT interval at the time of maximum drug concentration (21 days after injection) should be obtained in patients at risk. Hypokalemia or hypomagnesemia must be corrected prior to initiating SIGNIFOR LAR and should be monitored periodically during therapy.
  • DRUG INTERACTIONS
  • Effect of Other Drugs on SIGNIFOR LAR
  • Drugs That Prolong QT
  • Coadministration of drugs that prolong the QT interval with SIGNIFOR LAR may have additive effects on the prolongation of the QT interval. Monitoring effects on the QT interval at 21 days is recommended [see Warnings and Precautions (5.2)].
  • ADVERSE REACTIONS
  • Clinical Trials Experience
  • Other notable adverse reactions which occurred with a frequency of 5% or less for SIGNIFOR LAR were: adrenal insufficiency (3%); glucose tolerance impaired (1%); QT-prolongation (4%); blood amylase increased (2%).
  • Other adverse reactions which occurred at a frequency less than 5% were cholestasis (4%), glucose tolerance impaired (3%), aspartate aminotransferase increased (3%), vomiting (3%), lipase increased (3%), injection-site reactions (2%), ECG QT prolonged (1%), cholecystitis (1%), amylase increased (1%), and prothrombin time prolonged (1%).
  • CLINICAL PHARMACOLOGY
  • Pharmacodynamics
  • Cardiac Electrophysiology
  • Individually corrected QT (QTcI) interval was evaluated in a randomized, blinded, crossover study in healthy subjects investigating pasireotide subcutaneous doses of 0.6 mg and 1.95 mg twice daily, respectively. The maximum mean (95% upper confidence bound) placebo-subtracted QTcI change from baseline was 12.7 (14.7) ms and 16.6 (18.6) ms, respectively. Both pasireotide doses decreased heart rate, with a maximum mean (95% lower confidence bound) placebo-subtracted change from baseline of -10.9 (-11.9) beats per minute (bpm) observed at 1.5 hours for pasireotide 0.6 mg twice daily, and -15.2 (-16.5) bpm at 0.5 hours for pasireotide 1.95 mg twice daily.
  • PATIENT COUNSELING INFORMATION
  • Bradycardia and QT Prolongation
  • Advise patients that an ECG will be taken before treatment and periodically thereafter. Advise patients with cardiac disease and with risk factors for QT prolongation and bradycardia that adjustments in cardiac medications may be made and electrolyte disturbances may require correction [see Warnings and Precautions (5.2)].
  • PATIENT PACKAGE INSERT
  • Before you receive SIGNIFOR LAR, tell your healthcare provider about all of your medical conditions, including if you:
  • have high blood sugar (hyperglycemia).
  • have diabetes.
  • have or have had heart problems, including an abnormal heart rate or rhythm or problems with the electrical system of your heart (QT prolongation).
  • have a low level of potassium or magnesium in your blood.
  • have liver problems.
  • have gallstones (cholelithiasis).
  • are pregnant or plan to become pregnant. It is not known if SIGNIFOR LAR will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if SIGINFOR LAR passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take SIGNIFOR LAR.
  • changes in the electrical system of your heart (QT interval prolongation). Tell your healthcare provider if you get any of these symptoms:

Postmarketing Surveillance

Contingency Table:

Current Drug
Other Drugs
QT Prolongation
19
24073
Other ADRs
5559
38376028

Odds Ratio = 5.449

Drug Property Information



ATC Code(s):
  • H01CB05 - pasireotide
    • H01CB - Antigrowth hormones
    • H01C - HYPOTHALAMIC HORMONES
    • H01 - PITUITARY AND HYPOTHALAMIC HORMONES AND ANALOGUES
    • H - "SYSTEMIC HORMONAL PREPARATIONS, EXCL. "
Active Ingredient:PASIREOTIDE
Active Ingredient UNII:98H1T17066
Drugbank ID:DB06663
PubChem Compound:9941444
CTD ID: C517782
PharmGKB:
CAS Number:396091-73-9
Dosage Form(s):kit
Route(s) Of Administrator:intramuscular
Daily Dose:
  • 1.2 mg/day H01CB05
Chemical Structure:
SMILE Code:
NCCCC[C@@H]1NC(=O)[C@@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@@H]2C[C@H](CN2C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=C(OCC3=CC=CC=C3)C=C2)NC1=O)OC(=O)NCCN)C1=CC=CC=C1

Reference

1: Electrophysiological features in acromegaly: re-thinking the arrhythmic risk?

[Parolin M,Dassie F,Vettor R,Steeds R P,Maffei P]
J Endocrinol Invest,2021 Feb;44(2):209-221. PMID: 32632903

2: Pasireotide.


Prescrire Int,2013 Nov;22(143):257-9. PMID: 24427831

3: Pasireotide monotherapy in Cushing's disease: a single-centre experience with 5-year extension of phase III Trial.

[MacKenzie Feder Jessica,Bourdeau Isabelle,Vallette Sophie,Beauregard Hugues,Ste-Marie Louis-Georges,Lacroix André]
Pituitary,2014 Dec;17(6):519-29. PMID: 24287689

Disclaimer:

The content of this database of QT prolongation is intended for educational and scientific research purposes only. It is not intended as a substitute for professional medical advice, diagnosis or treatment.

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