Drug Interactions between acetaminophen / dextromethorphan / guaifenesin / oxymetazoline / phenylephrine and isoniazid

Using acetaminophen together with isoniazid may alter the effects of acetaminophen and cause serious side effects that may affect your liver. Call your doctor immediately if you experience a fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, or yellowing of the skin or the whites of your eyes. If your doctor does prescribe these medications together, you may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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GENERALLY AVOID: Coadministration of isoniazid (INH), with drugs that possess serotonergic activity (e.g., serotonin reuptake inhibitors, 5-HT1 receptor agonists, ergot alkaloids, etc.) may increase the risk of serotonin syndrome, a rare but serious and potentially fatal condition. The proposed mechanism is an increase in serotonin resulting from INH's weak inhibition of monoamine oxidase (the enzyme primarily responsible for breaking down norepinephrine, serotonin, and dopamine) combined with the increase in serotonin from the serotonergic drug(s). In one case report, a patient taking mirtazapine (15 mg nightly) for depression was started on INH (300 mg daily) and pyridoxine (25 mg daily) for tuberculosis prophylaxis following a liver transplant from a donor with latent tuberculosis. Six days following the initiation of INH, the patient developed symptoms consistent with serotonin syndrome (e.g., diarrhea, nausea, tremors, hypertension, and altered mental status) which resolved upon the cessation of INH and mirtazapine. However, consensus on the safety of concomitant use of isoniazid with drugs possessing serotonergic activity is lacking and most of the existing data are limited to case reports.

MANAGEMENT: Until more information is available, coadministration of isoniazid with drugs that possess serotonergic activity (e.g., serotonin reuptake inhibitors, 5-HT1 receptor agonists, ergot alkaloids, etc.) should generally be avoided. If coadministration with a serotonergic drug is required, patients should be advised to promptly seek medical attention if they experience signs and symptoms of serotonin syndrome (including but not limited to confusion, hallucinations, tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, neuromuscular abnormalities and/or unexplained gastrointestinal symptoms).

Consumer information for this interaction is not currently available.

MONITOR: By inhibiting the breakdown of catecholamines, monoamine oxidase inhibitors (MAOIs) may theoretically potentiate the cardiovascular effects of systemically absorbed sympathomimetic agents following topical administration (e.g., nasal decongestants, ophthalmic vasoconstrictors). However, the interaction has not been reported extensively in the medical literature. No increase in blood pressure or heart rate was observed when tranylcypromine was administered to a patient using 1% epinephrine eye drop twice a day. Most topical decongestants and vasoconstrictors are direct-acting sympathomimetics, which appear to be less affected by MAOIs than indirect- or mixed-acting sympathomimetics such as pseudoephedrine or ephedrine. While MAOI use has been reported to precipitate severe hypertensive reactions and hyperpyrexia in patients receiving indirect- or mixed-acting agents, most studies have found minimal effect on pressor response to systemically administered direct-acting agents including epinephrine, norepinephrine, and isoproterenol. Nevertheless, increased pressor effects and greater than 50% reductions in the required dosage of direct-acting agents have been reported in hypertensive patients who were being treated for MAOI-induced postural hypotension. There have also been occasional reports of increased blood pressure and heart rate in patients receiving systemic direct-acting agents and MAOIs.

MANAGEMENT: Although data are limited, caution may be advisable when topical decongestants and vasoconstrictors are coadministered with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine).