Fenfluramine Disease Interactions

The use of CNS stimulants can cause psychotic symptoms, suicidal ideation, and aggression, and can exacerbate symptoms of behavior disturbance and thought disorder; CNS stimulants may induce a manic or mixed episode in patients with bipolar disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders. All patients (particularly those with psychotic or bipolar disorders) should be monitored closely, especially during treatment initiation and at times of dose changes. Extreme caution should be exercised when CNS stimulants are given to patients with a history of psychosis, depression, mania, or bipolar disorder. Prior to initiating therapy, all patients should be screened for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or family history of suicide, bipolar disease, or depression). If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. Some CNS stimulants are contraindicated in patients with marked agitation or anxiety.

Serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine have been associated with valvular heart disease. Exercise care when using this agent in patients with cardiac disease. Cardiac monitoring is required prior to starting, during, and after treatment. If valvular heart disease is observed on an echocardiogram, the prescriber must consider the benefits versus the risks of initiating or continuing treatment. Echocardiograms should be repeated every six months, and once 3-6 months posttreatment.

Serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine, have been associated with pulmonary arterial hypertension. Exercise care when using this agent in patients with pulmonary disease. Cardiac monitoring is required before starting, during, and after treatment. Cardiac monitoring via echocardiogram can identify evidence of pulmonary arterial hypertension. If pulmonary arterial hypertension is observed on an echocardiogram, the prescriber must consider the benefits versus the risks of initiating or continuing treatment. Echocardiograms should be repeated every six months, and once 3-6 months posttreatment.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

Fenfluramine can cause somnolence, sedation, and lethargy. Central nervous system depressants, including alcohol, could potentiate these effects. Exercise caution when using this agent in alcoholic patients or those at risk of sedation. Close monitoring is advised. Advise patients not to drive or operate machinery until they know how this drug will affect them.

Fenfluramine can cause decreases in appetite and weight. Exercise care when using this agent in patients at risk of decreased appetite or weight. It is recommended to monitor the growth of pediatric patients carefully. Weight should be monitored regularly during treatment, and dose modifications should be considered if a decrease in weight is observed.

Fenfluramine can cause an increase in blood pressure. Exercise care when using this agent in hypertensive patients. It is recommended to monitor blood pressure in patients treated with fenfluramine.

Fenfluramine is primarily metabolized to norfenfluramine in the liver. The maximum daily dosage of 20 mg per day should not be exceeded in patients with mild and moderate liver dysfunction. Patients with severe liver dysfunction should not exceed 17 mg per day. The manufacturer prescribing information should be consulted for dose adjustment information of fenfluramine with other concomitant antiepileptic drugs.

Fenfluramine has not been studied in patients with end-stage renal disease (eGFR less than 15 mL/min/1.73 m2). In patients with severe renal dysfunction (eGFR 15 to 29 mL/min/1.73 m2) the maximum daily dosage of 20 mg per day should not be exceeded (17 mg per day if concomitant stiripentol is used). No dose adjustments are required for patients with mild and moderate renal dysfunction.

Fenfluramine can cause mydriasis and can precipitate angle-closure glaucoma. Exercise care when using this agent in patients with visual disturbances. Consider discontinuing treatment in patients with acute decrease in visual acuity or ocular pain.