Drug Interactions between Atamet and IsonaRif

Using isoniazid together with rifAMPin can 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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MONITOR: Coadministration of levodopa with isoniazid may reduce the therapeutic effects of levodopa, increase symptoms of polyneuropathy, and increase the risk of severe hypertensive reactions. While the mechanism of decreased levodopa efficacy by isoniazid is not fully understood, data from available medical literature suggests isoniazid is a nonspecific inhibitor of pyridoxal phosphate dependent enzymes, including dopa decarboxylase, the enzyme responsible for converting levodopa to therapeutically active dopamine. Polyneuropathy has been reported during treatment with levodopa-carbidopa combinations, and concurrent use of other medications that are also associated with this adverse effect may potentiate the risk and/or severity of nerve damage. In a systematic review evaluating the prevalence of peripheral polyneuropathy (PNP) with oral levodopa and levodopa/carbidopa intestinal gel infusion, PNP occurred in 30.2% and 42.1%, respectively. In both groups, there was an association between PNP and higher levodopa doses and biochemical alterations including increased homocysteine, reduced vitamin B12, increased methylmalonic acid, and reduced vitamin B6. The suspected mechanism behind isoniazid-induced peripheral neuropathy is related to isoniazid's interference with human vitamin B6 synthesis. One study suggests the risk of developing drug induced peripheral neuropathy increases with higher doses of INH and the presence of HIV infection. The authors observed that, with concomitant pyridoxine supplementation, this complication can be reversed within weeks to months. Isoniazid is also considered a weak inhibitor of monoamine oxidase (MAO) which is responsible for breaking down norepinephrine, serotonin, and dopamine. Combining INH with levodopa, a precursor to dopamine and norepinephrine, can theoretically lead to additive effects and increase the risk of hypertensive crises. However, data evaluating this aspect of the interaction are limited and speculative.

MANAGEMENT: If levodopa is used concurrently with isoniazid, patients should be monitored for a worsening of parkinsonian symptoms, and for signs and symptoms of hypertensive crisis (including but not limited to severe headache, visual disturbances, difficulty thinking, and chest pain). The product labeling for the enteral formulation of levodopa-carbidopa recommends evaluating patients for a history or signs of polyneuropathy and known risk factors such as diabetes mellitus, hypothyroidism, or concomitant use of other medications associated with polyneuropathy prior to treatment initiation. For patients with preexisting polyneuropathy, the benefits of treatment should be carefully weighed against the potential risks, including the potential for impaired mobility. Plasma concentrations of vitamin B12, vitamin B6, homocysteine, methylmalonic acid, and folic acid should be obtained at baseline and at regular intervals during treatment. Patients who develop symptoms of peripheral neuropathy and low plasma concentrations of vitamin B6 and/or vitamin B12, or elevated homocysteine or methylmalonic acid concentrations, may benefit from vitamin supplementation, but only if levodopa is coadministered with carbidopa as pyridoxine can decrease the amount of available levodopa that crosses the blood brain barrier.