Interactions between Pondimin and Sunitinib

SUNItinib has a moderate potential interaction with Adrenal Insufficiency.

Caution should be exercised when prescribing sunitinib in patients that elicit a stress response due to the hormonal and metabolic changes resulting from an injury, trauma, or a severe infection.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with Arrhythmia.

Sunitinib can cause QT prolongation in a dose-dependent manner, which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. This agent should be administered with caution in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Serum electrolytes should be corrected before initiating therapy with this agent. Periodic monitoring of ECGs and electrolytes is recommended in these patients.

SUNItinib has a moderate potential interaction with Bleeding Disorder.

The use of sunitinib has been associated with hemorrhagic events, some of which have been fatal. Caution should be exercised in patients with or predisposed to bleeding complications. Clinical assessment of these patients should include serial complete blood counts and physical examinations.

The fenfluramine in Pondimin 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.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with Dermatitis, Drug-Induced.

Cutaneous reactions, in some cases severe, have been reported with the use of sunitinib. Monitor patients who develop dermatologic or soft tissue toxicities while receiving this agent. It is recommended to withhold treatment, and appropriate measures should be instituted as appropriate or discontinue the use of this agent for dermatologic or soft tissue toxicity associated with severe or life-threatening complications. If a diagnosis of Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected treatment with sunitinib must not be re-started.

SUNItinib has a moderate potential interaction with Diabetes Mellitus.

The use of sunitinib has been associated with symptomatic hypoglycemia, resulting in loss of consciousness or hospitalization. Patients with diabetes mellitus should be monitored more closely during and after discontinuation of treatment with sunitinib, and their antidiabetic regimen should be adjusted accordingly.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with Heart Disease.

The use of sunitinib has been associated with adverse cardiovascular events, including heart failure, cardiomyopathy, myocardial ischemia, and myocardial infarction, some of which were fatal. Because of these risks, physicians are advised to weigh this risk against the potential benefits of the drug when prescribing this drug to patients with cardiovascular dysfunction. These patients should be carefully monitored and baseline and periodic evaluations of cardiovascular function should be considered while these patients are receiving sunitinib, especial caution is recommended in patients who are at risk for, or who have a history of cardiovascular events. In patients without cardiac risk factors, a baseline evaluation of ejection fraction should be considered.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with High Blood Pressure.

The use of sunitinib has been associated with hypertension and it should be used with caution in patients with elevated blood pressure. Therapy with sunitinib should be withheld in case of severe hypertension and appropriate measures should be taken to correct the blood pressure to acceptable readings. Close monitoring of blood pressure is recommended.

SUNItinib has a moderate potential interaction with Infection.

Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking sunitinib. Patients with risk factors, such as those taking bisphosphonate medications or that have a dental disease could be at an increased risk of developing ONJ. Close monitoring should be exercise when prescribing sunitinib to these patients.

SUNItinib has a moderate potential interaction with Infection.

Caution should be exercised when prescribing sunitinib in patients that elicit a stress response due to the hormonal and metabolic changes resulting from an injury, trauma, or a severe infection.

SUNItinib has a moderate potential interaction with Interstitial Lung Disease.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

SUNItinib has a major potential interaction with Liver Disease.

The use of sunitinib has been associated with hepatotoxicity, including hepatic failure and in some cases with fatal outcomes. Patients with hepatic impairment (total bilirubin > upper limit of normal (ULN) or Child-Pugh A, B and C) should be closely monitored during therapy with sunitinib. Safety in patients with ALT or AST >2.5 × ULN or, if due to liver metastases, >5.0 × ULN has not been established. Clinical monitoring of hepatic function (transaminases, bilirubin, and alkaline phosphatase) is recommended during treatment and increase frequency of monitoring is required for patients with preexisting or existing hepatic impairment. Obtain periodic liver function testing and withhold for Grade 3 or 4 drug-related hepatic adverse events. Discontinued if symptoms of pancreatitis or hepatic failure are present. Do not restart sunitinib if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure.

The fenfluramine in Pondimin 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.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with Proteinuria.

Therapy with sunitinib should be administered cautiously in patients with renal dysfunction. Monitoring for proteinuria and hematuria is recommended and perform baseline and periodic urinalyses during treatment, with follow up measurement as clinically indicated. Patients with nephrotic syndrome or repeat episodes of urine protein >=3 grams despite dose reductions should be instructed to withhold the dose of sunitinib and take appropriate actions according to clinical standards.

The fenfluramine in Pondimin 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.

The fenfluramine in Pondimin 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.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with Pulmonary Impairment.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with Renal Dysfunction.

No dosage adjustment of sunitinib is necessary in patients with renal impairment. However, when sunitinib therapy was given to patients with end-stage renal disease (ESRD) or on hemodialysis, the systemic exposure was 47% lower in subjects with ESRD on hemodialysis compared to subjects with normal renal function. Therefore, the subsequent doses may be increased gradually up to 2 fold based on safety and tolerability.

SUNItinib has a moderate potential interaction with Thyroid Disease.

Thyroid abnormalities, hypothyroidism or hyperthyroidism, have been reported in patients taking sunitinib. Therapy with sunitinib should be administered cautiously to patients with thyroid dysfunction. Baseline laboratory measurement of thyroid function is recommended and if appropriate, treatment per standard medical practice should be given prior to initiation of therapy. Clinical monitoring of thyroid function is recommended during therapy.

The fenfluramine in Pondimin 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.

SUNItinib has a moderate potential interaction with Ventricular Arrhythmia.

Sunitinib can cause QT prolongation in a dose-dependent manner, which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. This agent should be administered with caution in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Serum electrolytes should be corrected before initiating therapy with this agent. Periodic monitoring of ECGs and electrolytes is recommended in these patients.

The fenfluramine in Pondimin 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.