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Drug Interactions between HydroDIURIL and sparsentan

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

hydroCHLOROthiazide sparsentan

Applies to: HydroDIURIL (hydrochlorothiazide) and sparsentan

MONITOR: Concomitant use of sparsentan and antihypertensive drugs or drugs with hypotensive properties may result in additive blood pressure-lowering effects. Sparsentan is an endothelin and angiotensin II receptor antagonist. Hypotension has been observed in patients treated with angiotensin II receptor antagonists (ARBs) and endothelin receptor antagonists (ERAs) and was observed in clinical studies with sparsentan. In PROTECT, the randomized, double-blind, active-controlled clinical study in adults with primary immunoglobulin A nephropathy (IgAN), there was a greater incidence of significant hypotension-related adverse events, including orthostatic hypotension and dizziness in those treated with sparsentan compared to irbesartan.

MANAGEMENT: Caution and monitoring for hypotension and appropriate volume status is recommended if sparsentan is used in combination with antihypertensive medication or other medication with hypotensive effects. A dosage reduction or discontinuation of concomitant antihypertensive therapy should also be considered in patients at risk for hypotension. If hypotension develops despite dose reduction or cessation of concomitant antihypertensive therapy, a dose reduction or dose interruption of sparsentan should be considered. If the hypotensive response is transient, sparsentan may be administered once blood pressure has stabilized. Patients should be advised to contact their physician if they experience symptoms of hypotension such as dizziness, lightheadedness, or fainting.

References

  1. (2023) "Product Information. Filspari (sparsentan)." Travere Therapeutics Inc.

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Drug and food interactions

Major

sparsentan food

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.

MONITOR CLOSELY: 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: It may be advisable for patients to 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

  1. (2023) "Product Information. Filspari (sparsentan)." Travere Therapeutics Inc.

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Moderate

hydroCHLOROthiazide food

Applies to: HydroDIURIL (hydrochlorothiazide)

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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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.