FYREMADEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FYREMADEL (FYREMADEL).
FYREMADEL is a GLP-1 receptor agonist that activates GLP-1 receptors, increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner, and slows gastric emptying.
| Metabolism | FYREMADEL is metabolized via proteolytic cleavage by endogenous peptidases to smaller peptide fragments, not significantly metabolized by CYP450 enzymes. |
| Excretion | Renal: 60% unchanged; Biliary/Fecal: 30% as metabolites; 10% other. |
| Half-life | Terminal half-life: 12 hours (range 8–16 h) in healthy adults; prolonged in hepatic impairment. |
| Protein binding | 97% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8 L/kg (range 0.6–1.0 L/kg); indicates moderate tissue distribution. |
| Bioavailability | Oral: 45% (range 35–55%) due to first-pass metabolism. |
| Onset of Action | IV: 2–5 minutes; Oral: 30–60 minutes (fasted state). |
| Duration of Action | Analgesic effect lasts 4–6 hours after IV; 6–8 hours after oral dosing (dose-dependent). |
100 mg orally twice daily.
| Dosage form | INJECTABLE |
| Renal impairment | For GFR 30-89 mL/min: no adjustment; for GFR <30 mL/min: 50 mg orally twice daily. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 75 mg orally twice daily; Child-Pugh C: 50 mg orally twice daily. |
| Pediatric use | Not established; use not recommended. |
| Geriatric use | No specific adjustment; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FYREMADEL (FYREMADEL).
| Breastfeeding | No human data on excretion in breast milk. M/P ratio unknown. Potential for serious adverse effects in nursing infants, including immunosuppression and growth retardation. Breastfeeding is contraindicated during therapy and for at least 7 days after last dose. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: High risk of major congenital malformations including craniofacial defects, neural tube defects, and cardiovascular anomalies. Second/third trimester: Increased risk of spontaneous abortion, fetal growth restriction, and oligohydramnios. Contraindicated throughout pregnancy. |
■ FDA Black Box Warning
Risk of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC). FYREMADEL is contraindicated in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
| Serious Effects |
Personal or family history of MTC or MEN 2, known serious hypersensitivity to FYREMADEL or any excipients, and pregnancy (due to fetal risk).
| Precautions | Pancreatitis, acute gallbladder disease, hypoglycemia (especially when used with insulin or sulfonylureas), renal impairment (monitor renal function), hypersensitivity reactions, suicidal behavior or ideation (monitor), and increased heart rate. |
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| Fetal Monitoring | Pregnancy test prior to initiation and monthly during therapy. Ultrasound monitoring for fetal development monthly. Monitor for signs of fetal distress, growth restriction, and oligohydramnios. Serum drug levels to maintain therapeutic range. |
| Fertility Effects | May impair fertility in females due to ovarian suppression and menstrual irregularities. Reversible upon discontinuation. In males, may cause reduced spermatogenesis and decreased sperm motility. Infertility risk should be discussed before treatment. |