pasireotide (Rx)

Brand and Other Names:Signifor, Signifor LAR
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

SC injection solution (Signifor)

  • 0.3mg/mL
  • 0.6mg/mL
  • 0.9mg/mL

IM injection, powder for reconstitution (Signifor LAR)

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

Cushing Disease

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

Also see Administration

Signifor

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

Signifor LAR

  • 10 mg IM q4Week initially
  • After 4 months of treatment, the dose may be increased for patients who have not normalized 24-hr urinary free cortisol (UFC) and who tolerate this dose, up to a maximum dose of 40 mg IM q4Week

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

Also see Administration

Signifor LAR

  • 40 mg IM q4Week initially
  • If tolerated, may increase dose to up to 60 mg IM q4Week 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 (eg, 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 q4Weeks, 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 BID; not to exceed 0.6 mg SC BID
    • Moderate (Child-Pugh B), Signifor LAR: 10 mg IM q4Week; not to exceed 20 mg q4Week
    • Severe (Child-Pugh C): Avoid use
  • Acromegaly (Signifor LAR)
    • Mild (Child-Pugh A): No dose adjustment required
    • Moderate (Child-Pugh B): 20 mg IM q4Week; not to exceed 40 mg q4Week
    • 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

Safety and efficacy not established

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Interactions

Interaction Checker

and pasireotide

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (Signifor)

            Diarrhea (58-59%)

            Nausea (46-58%)

            Hyperglycemia (38-43%)

            Cholelithiasis (30%)

            Headache (28-29%)

            Abdominal pain (23-25%)

            Fatigue (15-24%)

            Diabetes mellitus (16-20%)

            Injection site reactions (17-18%)

            Asthenia (6-16%)

            Nasopharyngitis (12-14%)

            Increased alanine aminotransferase (ALT) (8-13%)

            Increased A1c (10-12%)

            >10% (Signifor LAR)

            Diarrhea (39%)

            Hyperglycemia (29%)

            Diabetes mellitus (26%)

            Cholelithiasis (26%)

            Headache (19%)

            Alopecia (18%)

            Abdominal pain (18%)

            Nasopharyngitis (16%)

            Nausea (14%)

            Increased creatinine phosphokinase (13-16%)

            Hypoglycemia (4-15%)

            Insomnia (4-14%)

            Abdominal distension (12%)

            Increased gamma-glutamyl transferase (9-12%)

            Upper abdominal pain (8-12%)

            Type 2 diabetes mellitus (6-12%)

            Myalgia (5-12%)

            Anxiety (6-11%)

            Influenza (6-11%)

            Peripheral edema (10-11%)

            Decreased appetite (9-11%)

            Hypercholesterolemia (9-11%)

            1-10% (Signifor)

            Hypertension (10%)

            Dizziness (9-10%)

            Arthralgia (5-10%)

            Vomiting (4-10%)

            Sinus bradycardia (3-10%)

            Pruritus (7-9%)

            ncreased lipase (6-9%)

            Constipation (5-9%)

            Hypotension (6-8%)

            Back pain (5-8%)

            Hypokalemia (5-7%)

            Pain in extremity (5-7%)

            Increased AST (4-7%)

            Increased blood glucose (4-7%)

            Dry skin (6%)

            Prolonged QT interval (6%)

            Vertigo (5-8%)

            Abdominal distension (5-6%)

            Adrenal insufficiency (5-6%)

            ncreased AST (6%)

            Increased blood glucose (6%)

            Anemia (4%)

            Increased amylase (2%)

            Prolonged PTT (2%)

            1-10% (Signifor LAR)

            Arthralgia (10%)

            Fatigue (10%)

            Dizziness (10%)

            Increased blood glucose (8%)

            Influenza (8%)

            Vomiting (8%)

            Hypertension (8%)

            Increased ALT (8%)

            Back pain (8%)

            Pain in extremity (7%)

            Upper respiratory infection (7%)

            Injection site reactions (7%)

            Increased glycosylated hemoglobin (6%)

            Upper abdominal pain (6%)

            Increased aspartate aminotransferase (AST) (6%)

            Decreased weight (5%)

            Cough (5%)

            Hypoglycemia (5%)

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            Warnings

            Contraindications

            None

            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 an for 4-6 weeks after a dose increase

            May cause 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 (eg, TSH/free T4, GH/IGF-1)

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            Pregnancy & Lactation

            Pregnancy

            Limited data with pasireotide in pregnant women are 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 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

            Discuss the potential for unintended pregnancy with premenopausal women 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

            Lactation

            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

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Cyclohexapeptide somatostatin analog; binds to human somatostatin receptors (hsst) 1, 2, 3, 4 and 5

            Absorption

            Peak plasma time: 0.25-0.5 hr

            Distribution

            Protein bound: 88%

            Vd: >100 L

            P-gp substrate (low)

            Metabolism

            Since somatropin increases CYP450 enzymes, suppression of growth hormone secretion by somatostatin analogs may decrease clearance of compounds metabolized by CYP450 enzymes

            Elimination

            Total body clearance: 3.8 L/hr

            Excretion: bile (main), renal (small)

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            Administration

            SC Administration (Signifor)

            Visually inspect solution for particulate matter and discoloration; do not use if particulates and/or discoloration observed

            Avoid injection in sites showing signs of inflammation or irritation

            Gently pinch skin at the injection site and hold the needle/syringe at an angle of approximately 45 degrees

            Administer SC by self-injection into the top of thigh or abdomen

            Rotate injection sites; use of the same injection site for 2 consecutive injections is not recommended

            Missed dose

            • If dose missed, next injection should be administered at the scheduled time; do not double doses to make up for a missed dose

            IM Preparation (Signifor LAR)

            Remove kit from refrigerator; allow kit to stand at room temperature for ≤30 minutes before starting reconstitution, but not more than 24 hr; kit may be re-refrigerated

            Attach vial adapter to vial; screw on syringe onto the vial adapter

            Push the plunger all the way down to transfer diluent into vial

            Shake vial moderately in a horizontal direction for a minimum of 30 seconds until powder is completely suspended; repeat moderate shaking for another 30 seconds if the powder is not completely suspended

            Draw entire contents from vial into the syringe and attach needle

            IM Administration (Signifor LAR)

            IM administration only, do not administer IV

            Remove kit from refrigerator and let it sit for at least 30 min (but not longer than 24 hr)

            Reconstitute with supplied diluent until powder is completely suspended (see package instructions)

            Insert the needle fully into the left or right gluteus at a 90° angle to the skin

            Slowly pull back the plunger to check that no blood vessel has been penetrated (reposition if a blood vessel has been penetrated)

            Slowly depress plunger until the syringe is empty

            Withdraw needle from injection site and activate the safety guard

            Missed dose

            • If a dose is missed and the patient returns prior to the next scheduled dose, dose may be given ≤14 days prior to next dose

            Storage

            Signifor

            • Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F), protect from light

            Signifor LAR

            • Unused kits: Refrigerate between 2–8°C (36–46°F); do not freeze; may also be left at room temperature for up to 24 hr
            • Diluted suspensions: Administer immediately
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.