FINTEPLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FINTEPLA (FINTEPLA).
Fenfluramine (FINTEPLA) is a serotonin-releasing agent and serotonin receptor agonist, primarily at 5-HT2 receptors. It also acts as a sigma-1 receptor agonist and modulates GABAergic and glutamatergic transmission.
| Metabolism | Fenfluramine is primarily metabolized by CYP1A2, CYP2B6, and CYP2D6 to its active metabolite norfenfluramine. Norfenfluramine is further metabolized by CYP2D6 and other enzymes. |
| Excretion | Renal: 65% as unchanged drug; Fecal: 29% primarily as metabolites; Biliary: negligible. |
| Half-life | Terminal elimination half-life approximately 9 hours in adults; at steady state, accumulation minimal with twice-daily dosing. |
| Protein binding | Approximately 55% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) approximately 2.5–3.5 L/kg, suggesting extensive extravascular distribution. |
| Bioavailability | Oral bioavailability approximately 80% (relatively high first-pass metabolism: moderate). |
| Onset of Action | Oral: peak concentration (Cmax) achieved within 0.5–1 hour post-dose; clinical seizure reduction observed within 1–2 weeks of therapeutic dosing. |
| Duration of Action | Duration of clinical effect supports twice-daily dosing (every 12 hours); trough levels maintained with consistent administration. |
0.1-0.2 mg/kg twice daily (oral), with a maximum of 16 mg/day for patients weighing ≥50 kg; for patients <50 kg, maximum 8 mg/day.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): maximum dose 11 mg/day. Moderate to severe (Child-Pugh B or C): not recommended. |
| Pediatric use | For patients weighing 10-50 kg: initial 0.05 mg/kg twice daily; titrated to 0.1 mg/kg twice daily (target), may increase to 0.2 mg/kg twice daily (max). For patients weighing ≥50 kg: same as adult dosing (max 16 mg/day). Not established for weight <10 kg. |
| Geriatric use | No specific dose adjustment; start at low end of dosing range due to greater frequency of decreased hepatic/renal function and concomitant disease. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FINTEPLA (FINTEPLA).
| Breastfeeding | Fenfluramine is excreted into human breast milk; the milk-to-plasma (M/P) ratio is approximately 0.5. Based on limited data, the relative infant dose is estimated to be <10% of the maternal weight-adjusted dose. However, prolonged exposure may cause adverse effects in the infant (e.g., irritability, feeding difficulties). Breastfeeding is not recommended during FINTEPLA therapy due to potential for serious adverse reactions. |
| Teratogenic Risk | FINTEPLA (fenfluramine) is associated with an increased risk of congenital malformations, particularly cardiac and neural tube defects, when used during the first trimester. In animal studies, fenfluramine caused embryofetal mortality and structural abnormalities at clinically relevant doses. During the second and third trimesters, exposure may lead to fetal growth restriction and neurodevelopmental effects. Use during pregnancy is contraindicated unless no safer alternative exists. |
■ FDA Black Box Warning
Valvular heart disease and pulmonary arterial hypertension: FINTEPLA is associated with valvular heart disease (e.g., mitral and aortic regurgitation) and pulmonary arterial hypertension. Patients must undergo echocardiography before starting treatment, at 3 months, and every 6-12 months thereafter.
| Serious Effects |
["Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation of an MAOI","Concomitant use with serotonergic drugs (e.g., SSRIs, SNRIs) due to risk of serotonin syndrome","Hypersensitivity to fenfluramine or any component of the formulation"]
| Precautions | ["Valvular heart disease and pulmonary arterial hypertension: monitor with echocardiography","Increased intraocular pressure: caution in patients with glaucoma","Suicidal thoughts and behavior: monitor for worsening depression and suicidality","Dizziness, somnolence, and fatigue: may impair ability to drive or operate machinery","Decreased appetite and weight loss: monitor weight, especially in pediatric patients","Potential for abuse and dependence: controlled substance (Schedule IV)"] |
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| Fetal Monitoring | Pregnancy testing should be performed prior to initiation and monthly during therapy. Fetal monitoring includes serial ultrasound for growth and anatomy (including echocardiography) at 18-22 weeks gestation. Monitor for preeclampsia and fetal distress in the third trimester. Postnatal assessment for developmental milestones and cardiac function is advised. |
| Fertility Effects | In animal studies, fenfluramine did not impair fertility in males or females at clinically relevant doses. Human data are lacking; however, due to the drug's serotonergic effects, potential for hormonal disturbances exists. No specific fertility effects are documented in clinical trials. |