pasireotide

Therapeutic Classification: hormones

Pharmacologic Classification: somatostatin analogues

REMS

Signifor:

Treatment of Cushing’s disease when surgery is not an option or has not resulted in cure

Signifor LAR:

Treatment of the following conditions:
- Acromegaly when surgery is not an option or has not resulted in an adequate response;
- Cushing’s disease when surgery is not an option or has not resulted in cure.

Acts as a somatostatin analogue. binding to and activating somatostatin receptors resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion.

Therapeutic Effects:

Improvement in clinical manifestations of Cushing's disease.
Reduction in growth hormone concentrations and normalization of insulin-like growth factor–1 concentrations.

Absorption: Unknown.

Distribution: Widely distributed, existing primarily in plasma.

Metabolism/Excretion: Eliminated mainly via hepatic clearance (biliary excretion) with small amounts renally excreted.

Half-life: 12 hr.

(†decrease in urinary free cortisol; ‡ blood levels)

ROUTE	ONSET	PEAK	DURATION
SUBQ†	within 1 mo	2 mo	unknown
IM‡	unknown	3 mo	unknown

†Decrease in urinary free cortisol.

‡Blood levels.

Contraindicated in:

Severe hepatic impairment (Child Pugh C).

Use Cautiously in:

Poorly controlled diabetes mellitus (blood sugar should be controlled prior to therapy)
Acute illness, infection, pancreatic surgery, pancreatic malignancy, or alcohol abuse (↑ risk of ketoacidosis)
Cardiac disease and/or risk factors for bradycardia including high-grade heart block, or concomitant use of drugs associated with bradycardia (dose adjustments of beta-blockers, calcium channel blockers, or correction of electrolyte disturbances may be necessary)
Patients at risk of QT interval prolongation, including congenital long QT prolongation, uncontrolled/significant cardiac disease including recent MI, HF, unstable angina or bradycardia, on antiarrhythmic therapy or other substances that are known to cause QT interval prolongation, hypokalemia and/or hypomagnesemia (correct prior to administration)
Moderate hepatic impairment (dose ↓ required)
OB: Lactation: Safety not established in pregnancy or lactation
Pedi: Safety and effectiveness not established in children
Geri: Initial lower dose recommended in older adults taking into account ↑ frequency of altered hepatic, renal, or cardiac function, concomitant diseases or other drug therapy.

CV: , hypertension, peripheral edema, , QT INTERVAL PROLONGATION, BRADYCARDIA, hypotension.

Derm: alopecia, injection site reactions, pruritus.

Endo: hyperglycemia, adrenal insufficiency, hypocortisolism, hypoglycemia, KETOACIDOSIS, pituitary hormone deficiency.

F and E: hypokalemia.

GI: abdominal pain, anorexia , cholelithiasis, diarrhea, nausea, ↑ amylase, ↑ liver enzymes, abdominal distention, cholecystitis, constipation, vomiting.

Hemat: ↑ prothrombin time, anemia.

Metab: ↑ lipase, hypercholesterolemia.

MS: arthralgia, back pain, extremity pain, myalgia.

Neuro: fatigue, headache, anxiety, dizziness, insomnia, vertigo.

Drug-Drug:

QT interval prolonging drugs ↑ risk of serious arrhythmias.
May ↓ absorption and effects of cyclosporine; dose adjustment of cyclosporine may be necessary.
May ↑ blood levels and effect of bromocriptine (dose ↓ of bromocriptine may be necessary).

Cushing's Disease

SC (Adults): Signifor: 0.6 mg or 0.9 mg twice daily (range 0.3–0.9 mg twice daily based on response/tolerability).

Hepatic Impairment

SC (Adults): Moderate hepatic impairment (Child Pugh B) (Signifor): 0.3 mg twice a day initially (max dose: 0.6 mg twice a day).
IM (Adults): Signifor LAR: 10 mg every 4 wk; after 4 mo, if inadequate response, may ↑ to 40 mg every 4 wk.

Hepatic Impairment

IM (Adults): Moderate hepatic impairment (Child Pugh B) (Signifor LAR): 10 mg every 4 wk; after 4 mo, if inadequate response, may ↑ to 20 mg every 4 wk.

Acromegaly

IM (Adults): Signifor LAR: 40 mg every 4 wk; after 3 mo, if inadequate response, may ↑ to 60 mg every 4 wk.

Hepatic Impairment

IM (Adults): Moderate hepatic impairment (Child Pugh B): 20 mg every 4 wk; after 3 mo, if inadequate response, may ↑ to 40 mg every 4 wk.

Powder for intramuscular injection (Signifor LAR): 10 mg/vial; 20 mg/vial; 30 mg/vial; 40 mg/vial; 60 mg/vial;
Solution for SUBQ injection (Signifor): 0.3 mg/mL; 0.6 mg/mL; 0.9 mg/mL;

Obtain a baseline ECG prior to starting and periodically during therapy. Monitor for QT interval prolongation. Correct hypokalemia and hypomagnesemia prior to therapy.
Perform an ultrasound of the gallbladder prior to therapy and at 6 and 12 mo intervals; cholelithiasis occurs frequently during therapy.
Monitor for signs and symptoms of hypocortisolism (weakness, fatigue, anorexia, nausea, vomiting, hypotension, hyponatremia, hypoglycemia) periodically during therapy. If hypocortisolism occurs, may require temporary dose reduction or interruption of therapy and exogenous glucocorticoid replacement.
Monitor patients with cardiac disease, history of significant bradycardia, high-grade heart block, or those taking drugs that may cause bradycardia for bradycardia. May require dose adjustments of beta blockers, calcium channel blockers, or correction of electrolyte imbalances.

Lab Test Considerations:

Monitor fasting plasma glucose, hemoglobin A1c and liver tests prior to starting therapy. Blood glucose and or fasting blood glucose should be self-monitored by patient weekly for first 2–3 mo and first 4–6 mo after dose increase, and periodically thereafter. If hyperglycemia occurs, may require initiation or adjustment of hypoglycemic agents.
- Monitor serum electrolytes (potassium, magnesium) prior to and periodically during therapy. Correct hypokalemia and hypomagnesemia before starting therapy and as needed.
- Monitor liver tests after 1–2 wks on therapy, then monthly for 3 months, and every 6 mo thereafter. If ALT is normal at baseline and ↑ of 3–5 times the upper limit of normal occur, repeat test in 1 wk or 48 hrs if >5 time upper limit of normal. If ALT is abnormal at baseline and ↑ of 3–5 times baseline level occur during therapy, repeat test within 1 wk or sooner if >5 time upper limit of normal. If levels are confirmed or rising, interrupt therapy and determine cause. Monitor ALT, AST, alkaline phosphatase, and total bilirubin weekly or more frequently if any level exceeds 5 times baseline level if abnormal baseline or 5 times upper limit of normal if baseline normal. If abnormalities resolve, resume therapy cautiously and monitor closely.
- Monitor pituitary function (TSH/free T₄, GH/IGF-1) prior to starting and periodically during therapy.
- May cause asymptomatic and reversible ↑ in amylase and lipase.
- May cause slight ↓ in hemoglobin and minimal ↑ in PT and PTT.

SC: Pinch skin and inject at 45° angle into top of thigh or abdomen. Place cotton ball or alcohol wipe over injection site and press for 5 seconds. Do not massage. Rotate sites; do not administer into site that is red or irritated. Solution is clear and colorless, do not inject solutions that are discolored or contain a precipitate.
IM: Allow vial to reach room temperature for at least 30 min, but not more than 24 hrs. Reconstitute with 2 mL diluent provided by manufacturer following manufacturer's instructions. Concentration: 10 mg/mL, 20 mg/mL, or 30 mg/mL based on dose.Shake vial moderately in horizontal position for at least 30 seconds until uniform suspension is formed; repeat shaking until all powder is completely suspended. Do not administer suspensions that are discolored or contain particulate matter. Inject slowly at a 90° angle into left or right gluteus. Missed dose may be given up until 14 days before next scheduled dose.

Instruct patient in correct technique for injection, care and disposal of equipment. Advise patient to read Medication Guide prior to using and with each Rx refill, in case of changes.
Advise patient to notify health care professional if signs and symptoms of hypocortisolism and hyperglycemia (excessive thirst, high urine output, increased appetite with weight loss, tiredness) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications
Rep: Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Therapy may cause improved fertility; discuss potential for unintended pregnancy with premenopausal women.

Reduction in 24-hour urinary free cortisol (UFC), typically seen in 2 mo.
- Improvement in signs and symptoms of Cushing's disease.
Reduction in growth hormone concentrations and normalization of insulin-like growth factor–1 concentrations in patients with acromegaly.

Signifor, Signifor LAR

NDC Code^*

0078- Novartis Pharmaceuticals Corporation
0078-0633- Signifor 0078-0633-20- 60 PACKAGE in 1 BOX (0078-0633-20) > 6 AMPULE in 1 PACKAGE (0078-0633-06) > 1 mL in 1 AMPULE (0078-0633-61)

0078- Novartis Pharmaceuticals Corporation
0078-0634- Signifor 0078-0634-20- 60 PACKAGE in 1 BOX (0078-0634-20) > 6 AMPULE in 1 PACKAGE (0078-0634-06) > 1 mL in 1 AMPULE (0078-0634-61)

0078- Novartis Pharmaceuticals Corporation
0078-0635- Signifor 0078-0635-20- 60 PACKAGE in 1 BOX (0078-0635-20) > 6 AMPULE in 1 PACKAGE (0078-0635-06) > 1 mL in 1 AMPULE (0078-0635-61)

0078- Novartis Pharmaceuticals Corporation
0078-0641- Signifor LAR 0078-0641-81- 1 KIT in 1 KIT (0078-0641-81) * 6 mL in 1 VIAL, SINGLE-USE (0078-0762-61) * 2 mL in 1 SYRINGE

0078- Novartis Pharmaceuticals Corporation
0078-0642- Signifor LAR 0078-0642-81- 1 KIT in 1 KIT (0078-0642-81) * 6 mL in 1 VIAL, SINGLE-USE (0078-0776-61) * 2 mL in 1 SYRINGE

0078- Novartis Pharmaceuticals Corporation
0078-0643- Signifor LAR 0078-0643-81- 1 KIT in 1 KIT (0078-0643-81) * 6 mL in 1 VIAL, SINGLE-USE (0078-0783-61) * 2 mL in 1 SYRINGE

0078- Novartis Pharmaceuticals Corporation
0078-0741- Signifor LAR 0078-0741-81- 1 KIT in 1 KIT (0078-0741-81) * 6 mL in 1 VIAL, SINGLE-USE (0078-0769-61) * 2 mL in 1 SYRINGE

0078- Novartis Pharmaceuticals Corporation
0078-0748- Signifor LAR 0078-0748-81- 1 KIT in 1 KIT (0078-0748-81) * 6 mL in 1 VIAL, SINGLE-USE (0078-0755-61) * 2 mL in 1 SYRINGE

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