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Interactions between Nefazodone and Sparsentan

1 drug interaction and 21 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

nefazodone sparsentan

Applies to: nefazodone and sparsentan
Generally avoid

Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations and risk of adverse reactions of sparsentan, which is primarily metabolized by the isoenzyme. Increased exposure to sparsentan may increase the risk and/or severity of serious adverse effects such as hepatotoxicity, acute kidney injury, hyperkalemia, edema, and hypotension. In clinical studies and model-informed approaches, concomitant use with the potent CYP450 3A4 inhibitor itraconazole increased sparsentan peak plasma concentration (Cmax) and systemic exposure (AUC) by 25% and 174%, respectively. Sparsentan alone may increase the risk for hepatotoxicity. It may be conceivable that concomitant use with potent CYP450 3A4 inhibitors that are also hepatotoxic may potentiate this risk. However, clinical data are not available.

Management

Coadministration of sparsentan with potent CYP450 3A4 inhibitors should be avoided. If concomitant use of a potent CYP450 3A4 inhibitor is considered to be clinically necessary, treatment with sparsentan should be interrupted. After discontinuation of the potent CYP450 3A4 inhibitor, sparsentan may be resumed via careful dose titration as recommended by the manufacturer. During treatment with sparsentan, close monitoring for clinical and laboratory evidence of hepatotoxicity is advised. Serum aminotransferase levels and total bilirubin should be monitored prior to sparsentan initiation and at regular intervals as recommended in the product labeling. Patients should be advised to notify their doctor if they experience signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Additional consultation with individual package labeling may be advisable for further guidance.

References (2)
  1. (2025) "Product Information. Filspari (sparsentan)." Travere Therapeutics Inc., 2
  2. (2025) "Product Information. Filspari (sparsentan)." Vifor Pharma UK Ltd, 2

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

sparsentan Food/Lifestyle

Applies to: sparsentan
Generally avoid

Grapefruit juice may increase the plasma concentrations of sparsentan, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Concomitant use with potent CYP450 3A4 inhibitor itraconazole increased sparsentan peak plasma concentration (Cmax) and systemic exposure (AUC) by 25% and 174%, respectively. Increased exposure to sparsentan may increase the risk of hepatotoxicity, acute kidney injury, hyperkalemia, edema, and hypotension. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

Generally avoid

Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using an endothelin and angiotensin II receptor antagonist such as sparsentan. Sparsentan can promote hyperkalemia through inhibition of the renin-angiotensin-aldosterone system (RAAS). Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia. Administration of a single oral dose of sparsentan 800 mg following a high-fat, high-calorie meal (1000 kcal, 50% fat), increased sparsentan AUC and Cmax by 22% and 108%, respectively. However, no clinically significant differences in sparsentan pharmacokinetics were observed following administration of a single 200 mg dose with a high-fat, high-calorie meal.

Management

Patients should avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with sparsentan. Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs. Advise patients to take the daily dose of sparsentan with water prior to either the morning or evening meal, and to maintain the same dosing schedule with respect to the time of day and in relation to meals.

References (2)
  1. (2025) "Product Information. Filspari (sparsentan)." Travere Therapeutics Inc., 2
  2. (2025) "Product Information. Filspari (sparsentan)." Vifor Pharma UK Ltd, 2

Moderate food/lifestyle interactions

Moderate:

nefazodone Food/Lifestyle

Applies to: nefazodone
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.

Disease interactions

19 potential interactions Applies to: 16 conditions, including Depression, Bipolar Disorder, Heart Failure, Seizures, and Diarrhea.

Bipolar Disorder

Moderate:

nefazodone

Nefazodone has a moderate potential interaction with Bipolar Disorder.

All antidepressants may occasionally cause mania or hypomania, particularly in patients with bipolar disorder. Therapy with antidepressants should be administered cautiously in patients with a history of mania/hypomania.

Moderate:

nefazodone

Nefazodone has a moderate potential interaction with Bipolar Disorder.

Adults, young adults and children patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. Phenylpiperazine antidepressants are not approved for use in pediatric patients.

Cerebrovascular Insufficiency

Major:

nefazodone

Nefazodone has a major potential interaction with Cerebrovascular Insufficiency.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Dehydration

Major:

nefazodone

Nefazodone has a major potential interaction with Dehydration.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Depression

Moderate:

nefazodone

Nefazodone has a moderate potential interaction with Depression.

Adults, young adults and children patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. Phenylpiperazine antidepressants are not approved for use in pediatric patients.

Diarrhea

Major:

nefazodone

Nefazodone has a major potential interaction with Diarrhea.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Glaucoma, Narrow Angle

Moderate:

nefazodone

Nefazodone has a moderate potential interaction with Glaucoma, Narrow Angle.

Some antidepressants exert mydriatic activity that can induce increased intraocular pressure and result in angle-closure (narrow-angle) glaucoma in a patient with anatomically narrow angles who does not have a patent iridectomy. Prior to initiating therapy with these agents, patients should be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible. The use of these drugs in patients with untreated anatomically narrow angles should be avoided.

Heart Failure

Moderate:

sparsentan

Sparsentan has a moderate potential interaction with Heart Failure.

Sparsentan has not been studied in patients with heart failure. Fluid retention may occur with endothelin receptor antagonists, including this drug. If fluid retention develops, modifications such as dose adjustment of sparsentan or diuretics may be required.

History - Cerebrovascular Disease

Major:

nefazodone

Nefazodone has a major potential interaction with History - Cerebrovascular Disease.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

History - Myocardial Infarction

Major:

nefazodone

Nefazodone has a major potential interaction with History - Myocardial Infarction.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Hypotension

Major:

nefazodone

Nefazodone has a major potential interaction with Hypotension.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Moderate:

sparsentan

Sparsentan has a moderate potential interaction with Hypotension.

Sparsentan may cause hypotension. In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status.

Ischemic Heart Disease

Major:

nefazodone

Nefazodone has a major potential interaction with Ischemic Heart Disease.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Liver Disease

Major:

nefazodone

Nefazodone has a major potential interaction with Liver Disease.

In general, treatment with nefazodone should not be initiated in patients with active liver disease or elevated baseline serum transaminase levels. Cases of hepatic failure resulting in death or liver transplant, at an estimated rate of 1 per 250,000 to 300,000 patient-years of nefazodone treatment in the U.S. (approximately 3 to 4 times the background rate), have been reported during postmarketing use. The time to liver injury for the reported cases typically ranged from 2 weeks to 6 months of use. Dark urine and nonspecific prodromal symptoms (e.g., nausea, anorexia, malaise, gastrointestinal complaints) were reported in some, but not all, cases prior to the onset of jaundice. There is no evidence that preexisting liver disease increases the likelihood of developing liver failure. However, baseline abnormalities can delay the recognition or confound the diagnosis of a drug-induced hepatotoxic effect, thus use of nefazodone is discouraged in this population. In patients who do receive nefazodone therapy, routine liver function testing should be considered to permit early detection of hepatic injury. Nefazodone therapy should be promptly discontinued if clinical signs or symptoms suggestive of liver injury occur, or if serum transaminase levels exceed 3 times the upper limit of normal. Therapy should be permanently discontinued in patients with presumed or confirmed drug-induced hepatotoxicity. In addition, the use of nefazodone is contraindicated in patients who were withdrawn from nefazodone because of evidence of liver injury.

Major:

sparsentan

Sparsentan has a major potential interaction with Liver Disease.

Endothelin receptor antagonists (ERAs) have been associated with aminotransferase elevations, hepatotoxicity, and cases of liver failure. Hepatic function should be assessed before treatment initiation and closely monitored during treatment. Therapy should be discontinued if aminotransferase elevations are accompanied by increases in bilirubin, or clinical symptoms of hepatotoxicity such as nausea, vomiting, fever, abdominal pain or jaundice. Treatment should be avoided in patients with elevated aminotransferases at baseline as monitoring for hepatotoxicity may be more difficult. In general, the use of ERAs is not recommended for patients with moderate to severe hepatic impairment.

Mania

Moderate:

nefazodone

Nefazodone has a moderate potential interaction with Mania.

All antidepressants may occasionally cause mania or hypomania, particularly in patients with bipolar disorder. Therapy with antidepressants should be administered cautiously in patients with a history of mania/hypomania.

Renal Dysfunction

Moderate:

sparsentan

Sparsentan has a moderate potential interaction with Renal Dysfunction.

Sparsentan is associated with a risk of renal impairment, including acute kidney injury, and hyperkalemia. Patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion may be at particular risk of developing acute kidney injury or hyperkalemia. Monitor renal function periodically.

Seizures

Moderate:

nefazodone

Nefazodone has a moderate potential interaction with Seizures.

The use of most antidepressants is associated with a risk of seizures. There have been only rare reports of convulsions, including grand mal seizures, following the administration of nefazodone or trazodone. Although a causal relationship has not been established, therapy with these agents should be administered cautiously in patients with a history of seizures.

Vomiting

Major:

nefazodone

Nefazodone has a major potential interaction with Vomiting.

Nefazodone has alpha-1 adrenergic blocking activity and may cause significant decreases in blood pressure, including orthostatic hypotension, in approximately 5% of patients. Therapy with nefazodone should be administered cautiously in patients with preexisting hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with nefazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

More resources

nefazodone

A total of 819 drugs are known to interact with nefazodone.

sparsentan

A total of 689 drugs are known to interact with sparsentan.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.