FINTEPLA
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 300.29 |
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 | Avoid use during first trimester due to potential teratogenicity; limited human data, but animal studies show increased risk of structural abnormalities. |
| 2nd trimester | Use only if benefit outweighs risk; may be associated with fetal growth restriction and neurodevelopmental effects. |
| 3rd trimester | Avoid near term due to risk of neonatal withdrawal and respiratory depression; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for FINTEPLA (FINTEPLA).
| Placental transfer | FINTEPLA crosses the placenta; animal studies demonstrate transfer with fetal exposure approximately equivalent to maternal plasma levels. Human data limited but suggests similar degree of transfer. |
| Breastfeeding | FINTEPLA is excreted into breast milk at low concentrations. Due to potential for serious adverse effects (e.g., sedation, feeding difficulties), breastfeeding is not recommended during therapy. Discontinue breastfeeding or discontinue drug, considering importance of drug to mother. |
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to fenfluramine or any component of formulationConcurrent use with or within 14 days of MAOIsHistory of pulmonary hypertension
| 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) |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they are CYP1A2 inhibitors and may increase fenfluramine exposure. No other significant food interactions reported. |
| Clinical Pearls | FINTEPLA (fenfluramine) is indicated for seizures associated with Dravet syndrome. Monitor for valvular heart disease and pulmonary arterial hypertension due to serotonergic effects; obtain baseline and periodic echocardiograms. Titrate slowly to minimize appetite suppression and weight loss. Avoid concurrent use with monoamine oxidase inhibitors (MAOIs) or other serotonergic drugs due to risk of serotonin syndrome. Dose adjustment required in hepatic impairment. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly as withdrawal may increase seizure frequency. · Common side effects include decreased appetite, weight loss, diarrhea, and fatigue. · Report any signs of heart problems such as shortness of breath, chest pain, or swelling of ankles. · Avoid grapefruit and grapefruit juice during treatment as it may increase drug levels. · Women of childbearing potential should use effective contraception due to potential fetal harm. · Do not drive or operate heavy machinery until you know how the medication affects you. |
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