SIGNIFOR LAR KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SIGNIFOR LAR KIT (SIGNIFOR LAR KIT).
Somatostatin analog that binds to somatostatin receptors (primarily sst2 and sst5), inhibiting growth hormone (GH) and insulin-like growth factor 1 (IGF-1) secretion, and reducing hormone release from neuroendocrine tumors.
| Metabolism | Metabolized by peptidases and not significantly via CYP450 enzymes. |
| Excretion | Primarily renal (approximately 85% of administered dose excreted unchanged in urine); minimal biliary/fecal excretion (less than 10%). |
| Half-life | Terminal elimination half-life following intramuscular injection of the long-acting formulation is approximately 19 days (range 15–23 days), supporting monthly dosing intervals. |
| Protein binding | Approximately 75% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Steady-state volume of distribution (Vd) is approximately 2.2 L/kg (total Vd ~200 L for a 70 kg patient), indicating extensive extravascular distribution. |
| Bioavailability | Absolute bioavailability for intramuscular injection (LAR formulation) is approximately 80% compared to subcutaneous administration; subcutaneous bioavailability is approximately 100% (reference for immediate-release formulation, but LAR is only for IM use). For the LAR kit, only IM route is relevant, with near complete release over 4 weeks. |
| Onset of Action | Administration via intramuscular injection as long-acting release: clinical effect (suppression of growth hormone and insulin-like growth factor-1) observed within 1–3 months after first injection, with maximal suppression typically by 3 months. |
| Duration of Action | Duration of clinical effect (suppression of GH/IGF-1) persists for approximately 3–4 weeks following a single intramuscular injection, consistent with monthly dosing schedule. Clinical response maintained with continued monthly administration. |
Intramuscular injection: 40 mg every 28 days.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use with caution. |
| Liver impairment | Child-Pugh A: 40 mg every 28 days. Child-Pugh B: 20 mg every 28 days. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; higher incidence of decreased renal function, monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SIGNIFOR LAR KIT (SIGNIFOR LAR KIT).
| Breastfeeding | No data on pasireotide excretion in human milk. M/P ratio unknown. Due to potential serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 3 months after the last dose. |
| Teratogenic Risk | Pregnancy category C. In animal studies, pasireotide (component of SIGNIFOR LAR KIT) caused embryotoxicity and fetal abnormalities at clinically relevant doses. In humans, limited data; risk of fetal harm cannot be ruled out. First trimester: potential teratogenic effects. Second/third trimesters: possible fetal growth restriction and metabolic disturbances due to maternal cortisol suppression. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to pasireotide or any component of the formulation"]
| Precautions | ["Gallbladder abnormalities (cholelithiasis) due to inhibition of gallbladder motility and bile secretion","Hyperglycemia and hypoglycemia due to alteration of glucose metabolism","Cardiac effects including bradycardia and QT prolongation","Pituitary apoplexy in patients with pituitary tumors","Gallbladder sludge or stones require monitoring"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood glucose and HbA1c for hyperglycemia/diabetes; liver function tests; serum cortisol and clinical signs of hypocortisolism; fetal growth ultrasound and amniotic fluid volume assessment due to risk of intrauterine growth restriction. Consider monitoring for QT prolongation in high-risk patients. |
| Fertility Effects | Pasireotide may suppress pituitary hormones (LH, FSH), potentially impairing fertility in both men and women. Reversible upon discontinuation. In females, may cause menstrual irregularities including amenorrhea, anovulation. |