pasireotide

pas-REE-tide

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 (IGF-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.

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

‡↓in urinary free cortisol.

‡Plasma concentrations.

Contraindicated in:

Severe hepatic impairment.

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: 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 bloating, cholecystitis, constipation, fat malabsorption, steatorrhea, stool discoloration, vomiting

Hemat: ↑prothrombin time, anemia

Metab: ↑lipase, hypercholesterolemia, weight loss

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 (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 (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: 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 and periodically during therapy for cholelithiasis.
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 ↓ 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.
Monitor for steatorrhea (excess fat in stool), abdominal bloating, and weight loss.If new occurrence or worsening of these symptoms occurs,evaluate for pancreatic exocrine insufficiency and provide appropriate medical management.

Lab Test Considerations:

Monitor fasting plasma glucose, 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, first 4–6 mo after dose ↑, 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 wk on therapy, then monthly for 3 mo, and every 6 mo thereafter. If ALT is normal at baseline and ↑ of 3–5 times the upper limit of normal (ULN) occurs, repeat test in 1 wk or 48 hr if >5 times ULN. If ALT is abnormal at baseline and ↑ of 3–5 times baseline level occurs during therapy, repeat test within 1 wk or sooner if >5 time ULN. 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 ULN (if baseline normal). If abnormalities resolve, resume therapy cautiously and monitor closely.
- Monitor pituitary function (TSH/free T₄, growth hormone/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 aPTT.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
If a dose is missed, administer at next scheduled time. Do not double doses.
SC: Solution is clear and colorless; do not use if cloudy, discolored, or contains particulates. Rotate injection sites at least 2 inches away from last site; avoid multiple injections in same site within short periods of time. Preferred injection sites are top of thigh or abdomen.
IM: Allow vial to reach room temperature for ≥30 min, but not more than 24 hr. 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 ≥30 sec until uniform suspension is formed; repeat shaking until all powder is completely suspended. Do not administer suspensions that are discolored or contain particulates. Inject slowly into the gluteus maximus. Missed dose may be given up until 14 days before next scheduled dose.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient to notify health care professional of excessive thirst, high urine output, ↑ appetite with weight loss, or tiredness, or if they experience new or worsening symptoms of fat in their stool, stool discoloration, loose stools, or abdominal bloating.
Rep: Advise females of reproductive potential that therapy with pasireotide may result in improved fertility. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Reduction in 24-hr urinary free cortisol, typically seen in 2 mo.
- Improvement in signs and symptoms of Cushing's disease.
Reduction in growth hormone concentrations and normalization of IGF-1 concentrations in patients with acromegaly.

Signifor, Signifor LAR

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US Brand Names ⬆