pasireotide

(redirected from Signifor)

pasireotide

(pas-ree-tide) ,

Signifor

(trade name)

Classification

Therapeutic: hormones
Pharmacologic: somatostatin analogues
Pregnancy Category: C

Indications

Treatment of adult patients with Cushing’s disease for whom surgery is not an option or has not resulted in cure

Action

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.

Pharmacokinetics

Absorption: Well absorbed following subcutaneous administration.
Distribution: Widely distributed, existing primarily in plasma.
Metabolism and Excretion: Eliminated mainly via hepatic clearance (biliary excretion) with small amounts renally excreted
Half-life: 12 hr.

Time/action profile (decrease in urinary free cortisol)

ROUTEONSETPEAKDURATION
subcutwithin 1 mo2 mosunk

Contraindications/Precautions

Contraindicated in: Severe hepatic impairment (Child Pugh C); Lactation: Should not be used by breastfeeding mothers;
Use Cautiously in: Poorly controlled diabetes mellitus (blood sugar should be controlled prior to therapy); 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 prolonged QTc, including congenital long QT prolongation, uncontrolled/significant cardiac disease including recent MI, CHF, unstable angina or bradycardia, on anti-arrhythmic therapy or other substances that are known to prolong QTc, hypokalemia and/or hypomagnesemia (correct prior to administration); Geriatric: initial lower dose recommended taking into account ↑frequency of altered hepatic, renal, or cardiac function, concomitant diseases or other drug therapy; Obstetric: Use during pregnancy only if clearly needed; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • headache (most frequent)
  • anxiety
  • dizziness
  • insomnia
  • vertigo

Cardiovascular

  • bradycardia (life-threatening)
  • QT prolongation (life-threatening)
  • (most frequent)
  • hypertension (most frequent)
  • peripheral edema (most frequent)
  • hypotension

Gastrointestinal

  • abdominal pain (most frequent)
  • anorexia (most frequent)
  • cholelithiasis (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • abdominal distention
  • constipation
  • ↑ amylase
  • ↑ liver enzymes
  • vomiting

Dermatologic

  • alopecia (most frequent)
  • injection site reactions (most frequent)
  • pruritus

Endocrinologic

  • hyperglycemia (most frequent)
  • adrenal insufficiency
  • hypocortisolism
  • hypoglycemia
  • pituitary hormone deficiency

Fluid and Electrolyte

  • hypokalemia

Hematologic

  • anemia
  • ↑ prothrombin time

Metabolic

  • hypercholesterolemia
  • ↑ lipase

Musculoskeletal

  • athralgia
  • back pain
  • extremity pain
  • myalgia

Interactions

Drug-Drug interaction

Drugs that prolong the QT interval ↑ risk of serious arrhythmias. May ↓ absorption and effects of cyclosporine Concomitant administration of cyclosporine with pasireotide may decrease the relative (dose adjustment of cyclosporine may be necessary). May ↑blood levels and effect of bromocriptine (dose reduction of bromocriptine may be necessary).May ↑ blood levels and effects of drugs metabolized by CYP450 enzymes.

Route/Dosage

Subcutaneous (Adults) Initial dose—0.6 mg or 0.9 mg twice daily (range 0.3–0.9 mg twice daily based on response/tolerability).

Hepatic Impairment

(Adults) Moderate hepatic impairment (Child Pugh B)—0.3 mg twice a day initially,maximum dosage – 0.6 mg twice a day.

Availability

Solution for subcutaneous injection: 0.3 mg/mL in 1 mL single use, 0.6 mg/mL in 1 mL single use ampule, or, 0.9 mg/mL in 1 mL single use ampule

Nursing implications

Nursing assessment

  • 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 month 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 hypocortiosolism 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, heomglobin 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 months and periodically thereafter. If hyperglycemia occurs, may require initiation or adjustment of hypoglycemic agents.
    • Monitor serum electrolytes periodically during therapy.
    • Monitor liver tests after 1–2 wks on therapy, then monthly for 3 months, and every 6 months 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.

Potential Nursing Diagnoses

Deficient knowledge, related to disease process and medication regimen (Patient/Family Teaching)

Implementation

  • Subcutaneous: 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.

Patient/Family Teaching

  • 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
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Reduction in 24-hour urinary free cortisol (UFC), typically seen in 2 months.
    • Improvement in signs and symptoms of Cushing's disease.
References in periodicals archive ?
Novartis announced today that the US Food and Drug Administration (FDA) has approved Signifor long-acting release (LAR) (pasireotide) for injectable suspension, for intramuscular use, for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.
The approval of Signifor LAR, a next-generation somatostatin analog (SSA), helps address a critical unmet need among the acromegaly patient population.
They include treatments such as a Kalydeco from Vertex Pharmaceuticals Inc for a rare form of the lung disorder cystic fibrosis and Signifor from Novartis AG for Cushing's disease, caused by over-production of the hormone cortisol.
Pasireotide, which will be marketed as Signifor by Novartis Pharmaceuticals, is administered subcutaneously twice a day.
Swiss drug major Novartis AG (Novartis) announced that the US Food and Drug Administration has approved its Signifor long-acting release (LAR) for the treatment of acromegaly, a rare and life-threatening hormonal disorder.
Novartis announced today that the European Commission has approved Signifor (pasireotide) as a new long acting release formulation for once monthly intramuscular injection to treat adult patients with acromegaly for whom surgery is not an option or has not been curative and who are inadequately controlled on treatment with a first-generation somatostatin analogue (SSA).
This positive CHMP opinion for Signifor LAR formulation represents a significant step towards our goal of being able to offer adult patients with inadequately controlled acromegaly in the EU a much-needed alternative treatment option," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs.
Signifor LAR will take up market share from Sandostatin LAR before the patent expiry in 2017 -- Panobinostat in RRMM -- Sandoz growth to be driven by biosimilars and respiratory generics -- Key Milestone Table
Novartis today presented results from a pivotal Phase III trial of investigational therapy Signifor LAR (pasireotide LAR; SOM230) in patients with acromegaly for whom current standard of care provides inadequate disease control.
Novartis AG Analyst Notes On May 5, 2014, Novartis AG (Novartis) presented results from a pivotal Phase III trial of investigational therapy Signifor LAR (pasireotide LAR; SOM230) in patients with acromegaly for whom current standard of care provides inadequate disease control.
European and Japanese regulatory submissions and approvals of Afinitor, Tasigna, Signifor, Exjade, Jakavi and Glivec in various indications.
For the treatment of Cushing's disease, Signifor has been studied as a twice-daily subcutaneous (sc) injection and is currently being evaluated as a long-acting release (LAR), once-monthly intramuscular (IM) injection as part of a global Phase III program in Cushing's disease and acromegaly.