Interactions between Bortezomib and Fenfluramine

Fenfluramine has a moderate potential interaction with Alcoholism.

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.

Bortezomib has a moderate potential interaction with Dehydration.

There was an incidence of 8% of hypotension in patients receiving bortezomib therapy. Caution should be used when treating patients with history of hypotension, syncope, dehydration, or taking antihypertensive medication.

Fenfluramine has a major potential interaction with Depression.

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.

Fenfluramine has a moderate potential interaction with Depression.

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.

Bortezomib has a moderate potential interaction with Diabetes Mellitus.

Hypoglycemia and hyperglycemia was reported during clinical trials in diabetic patients in treatment with oral hypoglycemics and receiving bortezomib. Patients on oral antidiabetic agents may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication when using bortezomib.

Fenfluramine has a moderate potential interaction with Failure to Thrive.

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.

Bortezomib has a moderate potential interaction with Heart Disease.

Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have occurred during treatment with bortezomib, including in patients with no risk factors. Patients with risk factors for, or existing heart disease should be closely monitored. There have also been isolated cases of QT interval prolongation but causality has not been established.

Fenfluramine has a moderate potential interaction with High Blood Pressure.

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.

Bortezomib has a moderate potential interaction with Hypotension.

There was an incidence of 8% of hypotension in patients receiving bortezomib therapy. Caution should be used when treating patients with history of hypotension, syncope, dehydration, or taking antihypertensive medication.

Bortezomib has a moderate potential interaction with Liver Disease.

Cases of acute liver failure and other hepatic reactions such as hepatitis, increases in liver enzymes, and hyperbilirubinemia have been reported in patients receiving bortezomib. Monitoring is recommended and caution should be used when using bortezomib in patients with hepatic impairment. The exposure of bortezomib is increased in patients with moderate and severe hepatic impairment, and starting dose should be reduced in those patients.

Fenfluramine has a moderate potential interaction with Liver Disease.

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 a moderate potential interaction with Malnourishment.

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.

Bortezomib has a moderate potential interaction with Peripheral Neuropathy.

Bortezomib can cause peripheral neuropathy that is predominantly sensory; however cases of severe sensory and motor peripheral neuropathy have been also reported. Patients with preexisting symptoms (numbness, pain or burning feeling in hands or feet) may experience worsening symptoms during treatment. Patients should be monitored for symptoms of neuropathy, and a dose adjustment might be required in those patients that experience them.

Fenfluramine has a major potential interaction with Psychosis.

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.

Fenfluramine has a moderate potential interaction with Psychosis.

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 has a major potential interaction with Pulmonary Arterial Hypertension.

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.

Bortezomib has a moderate potential interaction with Pulmonary Heart or Vascular Disease.

There have been reports of Acute Respiratory Distress Syndrome (ARDS) and acute diffuse infiltrative pulmonary disease of unknown etiology in patients receiving bortezomib. Additionally, there have been reports of pulmonary hypertension associated with bortezomib administration in the absence of left heart failure or significant pulmonary disease. Treatment interruption should be considered in the event of new or worsening cardiopulmonary symptoms until a comprehensive diagnostic evaluation is conducted. Caution should be exercised when using bortezomib in patients with cardiopulmonary pathologies.

Fenfluramine has a moderate potential interaction with Renal Dysfunction.

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 has a major potential interaction with Valvular Heart Disease.

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.

Fenfluramine has a moderate potential interaction with Visual Defect/Disturbance.

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.