SIGNIFOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SIGNIFOR (SIGNIFOR).
Somatostatin analog; inhibits growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other hormones.
| Metabolism | Primarily hepatic via CYP3A4; undergoes hydrolysis and reduction. |
| Excretion | Primarily renal (approximately 80% of the dose excreted unchanged in urine), with about 20% eliminated via biliary/fecal routes. Renal clearance accounts for ~70% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 5-6 hours in healthy subjects. In patients with renal impairment, half-life may be prolonged (up to 10 hours in severe impairment). |
| Protein binding | Approximately 88% bound to plasma proteins, primarily to alpha-1-acid glycoprotein and serum albumin. |
| Volume of Distribution | Volume of distribution is about 0.8-1.0 L/kg, indicating distribution into extracellular fluid and some tissue binding. High Vd suggests significant tissue penetration. |
| Bioavailability | Subcutaneous: Approximately 70-80% bioavailability. Oral bioavailability is negligible (<1%) due to extensive gastrointestinal degradation. |
| Onset of Action | Subcutaneous: Onset of reduction in ACTH and cortisol levels is within 30-60 minutes. Peak effect observed at 1-2 hours post-dose. |
| Duration of Action | Subcutaneous: Duration of cortisol suppression is approximately 6-8 hours after a single dose, supporting twice-daily or three-times-daily dosing regimens. Continuous infusion may provide sustained suppression over 24 hours. |
Subcutaneous injection: 0.3 mg twice daily; Intravenous bolus: 0.9 mg (for Cushing's disease perioperatively).
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), use with caution; no specific dose recommendation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Not recommended. |
| Pediatric use | Not approved for use in pediatric patients; no established dosing guidelines. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor renal function as elderly may have decreased renal clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SIGNIFOR (SIGNIFOR).
| Breastfeeding | It is not known whether pasireotide is excreted in human milk. However, pasireotide is detected in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Signifor, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. The M/P ratio is unknown. |
| Teratogenic Risk | Pregnancy Category C. Based on animal studies, Signifor (pasireotide) may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, pasireotide was teratogenic and embryotoxic at doses below the maximum recommended human dose. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Fetal risks may include skeletal abnormalities, reduced fetal weight, and increased fetal mortality, particularly in the first trimester. Due to its suppression of growth hormone and IGF-1, potential risks in the second and third trimesters include fetal growth restriction. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to pasireotide or excipients","Severe hepatic impairment (Child-Pugh class C)"]
| Precautions | ["Cholelithiasis: Monitor for gallstones.","Hyperglycemia/Hypoglycemia: Monitor blood glucose.","Bradycardia: Risk of heart rate alterations.","QT prolongation: Use caution with other QT-prolonging drugs.","Hypopituitarism: May cause hypocortisolism."] |
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| Fetal Monitoring | Monitor maternal blood glucose levels closely due to hyperglycemia risk. Assess for symptoms of cholelithiasis (abdominal pain, nausea/vomiting) and monitor liver function tests, as gallstones and elevated transaminases have been reported. Monitor fetal growth via ultrasound due to potential growth restriction. Consider monitoring maternal cardiac function as bradycardia and QT prolongation have been reported. |
| Fertility Effects | Signifor may impair fertility in females and males due to its suppression of the GH/IGF-1 axis and potential effects on gonadotropin secretion. In animal studies, pasireotide caused prolonged estrus cycles, decreased corpora lutea, and reduced fertility in females, and decreased sperm motility and fertility in males. These effects may be reversible upon discontinuation. |