Pasireotide

Pasireotide is used to treat Cushing disease and acromegaly.

Pasireotide is available under the following different brand names: Signifor and Signifor LAR.

Dosage Forms and Strengths

Subcutaneous (SC) Injection Solution (Signifor)

• 0.3 mg/mL
• 0.6 mg/mL
• 0.9 mg/mL

Intramuscular (IM) Injection, Powder for Reconstitution (Signifor LAR)

• 20 mg/vial
• 40 mg/vial
• 60 mg/vial

Cushing Disease

• Indicated for treatment of adults with Cushing disease in whom pituitary surgery is not an option or has not been curative

Signifor

• 0.6-0.9 mg subcutaneously (SC) twice daily initially; titrate dose based on response and tolerability
• If started on 0.6 mg twice daily, a dosage increase to 0.9 mg twice daily may be considered if treatment tolerated; dosage range: 0.3-0.9 mg SC twice daily

Signifor LAR

• 10 mg intramuscularly (IM) every 4 weeks initially
• After 4 months of treatment, the dose may be increased for patients who have not normalized 24-hour urinary free cortisol (UFC) and who tolerate this dose, up to a maximum dose of 40 mg IM every 4 weeks

Acromegaly

• Indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option

Signifor LAR

• 40 mg IM every 4 weeks initially
• If tolerated, may increase dose to up to 60 mg IM every 4 weeks 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 40 mg

Dosage Modifications

Adverse reactions or over-response

• Cushing disease
  • Adverse effects or over-response to treatment (e.g., cortisol levels)
  • Signifor: May require temporary dose reduction; dose reduction by 0.3 mg decrements per injection is suggested
  • Signifor LAR: If dose is 10 mg IM every 4 weeks, the dose may be either interrupted or discontinued
• Acromegaly (Signifor LAR)
  • Adverse reactions or over-response to treatment (age and sex adjusted IGF-1 )
  • Decreased dose, either temporarily or permanently, by 20-mg decrements

Hepatic impairment

• Cushing disease
  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate (Child-Pugh B), Signifor: 0.3 mg SC twice daily; not to exceed 0.6 mg SC twice daily
  • Moderate (Child-Pugh B), Signifor LAR: 10 mg IM every 4 weeks; not to exceed 20 mg every 4 weeks
  • Severe (Child-Pugh C): Avoid use

• Acromegaly (Signifor LAR)
  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate (Child-Pugh B): 20 mg IM every 4 weeks; not to exceed 40 mg every 4 weeks
  • Severe (Child-Pugh C): Avoid use

Dosing Considerations

• Evaluation for treatment response is based on reduction in 24-hr urinary free cortisol levels and/or improvement in disease signs and symptoms
• Maximum urinary free cortisol reduction typically seen by 2 months of treatment
• Continue treatment as long as benefit is derived
• Intensively optimize antidiabetic therapy (if blood glucose poorly controlled) before initiating pasireotide

Baseline tests

• Obtain the following before initiating:
• Fasting plasma glucose
• Hemoglobin A1c
• Liver tests
• Electrocardiogram
• Gallbladder ultrasound
• Pediatric

Common side effects of Pasireotide include:

• Diarrhea
• Nausea
• High blood sugar (hyperglycemia)
• Gallstone formation
• Headache
• Abdominal pain
• Fatigue
• Diabetes mellitus
• Injection site reactions
• Weakness/lethargy
• Runny or stuffy nose
• Increased alanine aminotransferase (ALT)
• Increased A1c
• High blood pressure (hypertension)
• Dizziness
• Joint pain
• Vomiting
• Slow heart rate
• Itching
• Increased lipase
• Constipation
• Low blood pressure (hypotension)
• Back pain
• Low blood potassium (hypokalemia)
• Pain in extremities
• Increased aspartate aminotransferase (AST)
• Increased blood glucose
• Dry skin
• Prolonged QT interval
• Spinning sensation (vertigo)
• Abdominal distension
• Adrenal insufficiency
• Anemia
• Increased amylase
• Prolonged PTT
• Hair loss
• Increased creatinine phosphokinase
• Low blood sugar (hypoglycemia)
• Insomnia
• Muscle pain
• Anxiety
• Influenza
• Swelling of extremities
• Decreased appetite
• High cholesterol
• Upper respiratory infection
• Increased glycosylated hemoglobin
• Weight loss
• Cough

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Severe interactions of pasireotide include:

• cisapride
• dronedarone
• pimozide
• thioridazine

Serious interactions of pasireotide include:

• entrectinib
• glasdegib
• inotuzumab
• ivosidenib
• macimorelin
• panobinostat
• pitolisant
• tacrolimus
• toremifene
• umeclidinium bromide/vilanterol inhaled
• vilanterol/fluticasone furoate inhaled
• vorinostat

Pasireotide has moderate interactions with at least 115 different drugs.

Pasireotide has no listed mild interactions with other drugs.

Warnings

This medication contains pasireotide. Do not take Signifor or Signifor LAR if you are allergic to pasireotide or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• None

Effects of Drug Abuse

• No information available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Pasireotide?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Pasireotide?"

Cautions

• Suppresses ACTH, which may lead to decreased cortisol and potential hypocortisolism
• Can cause increased blood glucose levels, which are sometimes severe; patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia; access fasting blood glucose and HgA1c before initiating and monitor blood glucose the first 3 months after initiating and for 4-6 weeks after a dose increase
• May cause slow heart rate (bradycardia) and QT prolongation; obtain baseline and periodic ECG, and potassium and magnesium levels; correct/supplement potassium and /or magnesium if clinically warranted
• Increased liver enzymes may occur and may require dose interruption and reduction
• Cholelithiasis reported; perform gallbladder ultrasound at baseline and at 6- to 12-months; if complications of cholelithiasis suspected, discontinue therapy and treat appropriately
• Monitor for pituitary hormone deficiency (e.g., TSH/free T4, GH/IGF-1)

Pregnancy and Lactation

The limited data with pasireotide in pregnant women is insufficient to inform a drug-associated risk for major birth defects and miscarriage. In embryofetal development studies in rabbits, findings indicating a developmental delay were observed with subcutaneous (SC) administration of pasireotide during organogenesis at doses less than the exposure in humans at the highest recommended dose; maternal toxicity was not observed at this dose.

The potential for unintended pregnancy in premenopausal women is possible as the therapeutic benefits of a reduction in growth hormone (GH) levels and normalization of insulin-like growth factor (IGF-1) in acromegalic females treated with pasireotide may lead to improved fertility.

There is no information available on the presence of pasireotide in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Studies show that pasireotide administered subcutaneously passes into the milk of lactating rats; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. Consult your doctor.