Drug Interactions between Fiorinal with Codeine III and sparsentan

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

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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.

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MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effects of angiotensin II receptor antagonists. The proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis, which results in unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects blood pressure. Clinical data are limited.

MONITOR: Concomitant use of NSAIDs and angiotensin II receptor antagonists may cause deterioration in renal function, particularly in patients who are elderly or volume-depleted (including those on diuretic therapy) or have compromised renal function. Acute renal failure may occur, although effects are usually reversible. Chronic use of NSAIDs alone may be associated with renal toxicities, including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. Additionally, in patients with prerenal conditions whose renal perfusion may be dependent on the function of prostaglandins, NSAIDs may precipitate overt renal decompensation via a dose-related inhibition of prostaglandin synthesis. Angiotensin II receptor antagonists can further worsen renal function by blocking the effect of angiotensin II-mediated efferent arteriolar vasoconstriction, thereby decreasing glomerular filtration.

MANAGEMENT: Patients receiving angiotensin II receptor antagonists who require prolonged (greater than 1 week) concomitant therapy with an NSAID should have blood pressure monitored more closely following initiation, discontinuation, or change of dosage of the NSAID. Renal function should also be evaluated periodically during prolonged coadministration. The interaction is not expected to occur with low doses (e.g., low-dose aspirin) or intermittent short-term administration of NSAIDs.

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MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of sparsentan, which is primarily metabolized by the isoenzyme. Concomitant use of rifampin, a potent CYP450 3A4 inducer, is predicted to decrease sparsentan peak plasma concentration (Cmax) and systemic exposure (AUC) by 23% and 47%, respectively at steady state. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of sparsentan should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

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One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

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