Signifor Lar (pasireotide pamoate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Pasireotide is a synthetic polypeptide pharmacologically related to somatostatin (growth hormone (GH, somatropin) release-inhibiting factor).
Pasireotide is a synthetic polypeptide that is pharmacologically related to the natural endocrine hormone somatostatin (growth hormone (GH, somatropin) release-inhibiting factor). The drug exerts its effects by binding to and activating somatostatin receptors in the anterior pituitary, resulting in inhibition of corticotropin (ACTH) secretion; among the 5 known human somatostatin receptor subtypes, pasireotide binds preferentially to somatostatin receptor subtypes 1, 2, 3, and 5, with greatest affinity for receptor subtype 5, which is frequently overexpressed in corticotroph tumor cells from patients with Cushing's disease. Suppression of ACTH secretion by pasireotide leads to decreased cortisol secretion from the adrenal glands.
In the treatment of acromegaly, pasireotide binds to somatostatin receptor subtypes 2 and 5, which may be relevant for inhibition of GH secretion. In vivo studies demonstrate that pasireotide lowers GH and IGF-1 concentrations in patients with acromegaly. Pasireotide differs from the currently available somatostatin analogs (lanreotide, octreotide) in its distinct somatostatin receptor-binding profile.
Following subcutaneous injection of pasireotide diaspartate, the drug exhibits linear pharmacokinetics and is rapidly absorbed with peak plasma concentrations occurring within 0.25-0.5 hours. The effective half-life of the drug is approximately 12 hours in healthy individuals. Following IM injection of long-acting pasireotide pamoate injectable suspension, the drug is released slowly and gradually from its polymer vehicle (after an initial, rapid absorption of immediately available drug) with peak plasma concentrations occurring around day 21; steady-state plasma concentrations are achieved after 3 monthly doses.
Studies using human liver and kidney microsomes indicate that pasireotide is not appreciably metabolized; in healthy individuals, the drug was detected mainly in its unchanged form in plasma, urine, and feces. Pasireotide is eliminated principally via hepatic (e.g., biliary) clearance; renal excretion appears to play only a minor role in elimination of the drug. Approximately 88% of the drug is bound to plasma proteins.
Pasireotide is commercially available in the US as pasireotide diaspartate (Signifor(R)) in a subcutaneous formulation for use in the treatment of Cushing's disease. Pasireotide is also available as the pamoate salt in a long-acting IM formulation (Signifor(R) LAR) for use in the treatment of acromegaly or Cushing's disease. Pasireotide has been designated an orphan drug by FDA for these uses.
Generic name: pasireotide pamoate
Pronunciation: (PAS-i-REE-oh-tide)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Signifor Lar
Indications
The following indications are listed for Signifor Lar:
- Acromegaly
- Hypercortisolism
Also known as: Acromegalia, Cushing Syndrome, Cushing's Basophilism, Hypercorticism, Marie's Disease, Marie's Syndrome.
Dosing
Dosage of pasireotide diaspartate and pasireotide pamoate is expressed in terms of pasireotide.
Pasireotide is commercially available as pasireotide diaspartate and pasireotide pamoate. The diaspartate salt form is available as a subcutaneous injection and the pamoate salt form is available as a long-acting suspension for IM injection.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
In vitro studies indicate that pasireotide is not a substrate, inhibitor, or inducer of any major cytochrome P-450 (CYP) isoenzymes. However, since pasireotide suppresses growth hormone (GH, somatropin) secretion and GH is known to increase activity of CYP isoenzymes, there is a possibility that pasireotide may decrease metabolic clearance of drugs metabolized by CYP isoenzymes.
The manufacturer states that pasireotide is not expected to be a substrate of the efflux transporter breast cancer resistance protein (BCRP) and also not likely to be a substrate of the influx transporters organic cation transporter 1 (OCT1) or organic anion-transporting polypeptide (OATP) 1B1, 1B3, or 2B1 at therapeutic dosages.
In vitro studies indicate that pasireotide is likely to be a substrate of the efflux transporter P-glycoprotein (P-gp); however, P-gp is expected to have a limited impact on the pharmacokinetics of pasireotide.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 20% or more of patients receiving pasireotide diaspartate subcutaneous injection in clinical trials include diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes mellitus.
Adverse effects reported in 20% or more of patients receiving pasireotide pamoate long-acting injectable IM suspension in clinical trials include diarrhea, cholelithiasis, hyperglycemia and diabetes mellitus.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of pasireotide have not been established in pediatric patients.
Limited data with pasireotide in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.
In animal studies, findings indicating developmental delays were observed in rabbits receiving pasireotide in dosages resulting in exposures lower than those achieved in humans at the maximum recommended dosage. Retardation of physiologic growth that was attributed to GH inhibition was observed in a pre- and post-natal study in rats; this developmental delay was reversible after weaning.
Pasireotide administered subcutaneously is distributed into milk in rats; it is not known whether the drug is distributed into human milk, affects milk production, or has any effects on the breast-fed infant.
The benefits of breast-feeding and the importance of pasireotide to the woman should be considered along with potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.
In general, dosage selection for geriatric patients should be cautious, usually starting at the low end of the dosage range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy observed in these individuals.
Clinical studies of pasireotide did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger adults. Other clinical experience has not revealed age-related differences in response. In general, dosage of pasireotide in geriatric patients should be selected with caution; dosage usually should be initiated at the low end of the dosage range because of the greater frequency of age-related decreases in hepatic, renal, and/or cardiac function, and of concomitant disease or other drug therapy. Age is not expected to substantially affect circulating levels of pasireotide.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.