Arava and Rifampin Intravenous

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Leflunomide may cause liver problems, and taking it with other medications that can also affect the liver such as rifAMPin may increase that risk. You should avoid or limit the use of alcohol while being treated with these medications. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. In addition, rifAMPin may increase the blood levels and effects of leflunomide, which may increase other serious side effects such as nerve damage and impaired bone marrow function resulting in low numbers of different types of blood cells. You may be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. Let your doctor know if you develop burning, numbness, tingling, or painful sensations in the arms, hands, legs, or feet. You may need a dose adjustment or more frequent monitoring by your doctor to safely use 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.

MONITOR CLOSELY: The recent, concomitant, or subsequent use (without the recommended leflunomide washout period or procedure) of other agents known to induce hepatotoxicity may potentiate the risk of liver injury associated with leflunomide. Elevated liver transaminases, hepatitis, jaundice/cholestasis, hepatic failure, and acute hepatic necrosis have been reported with leflunomide. Liver enzyme elevations were generally mild (2 times the upper limit of normal or less) and resolved while continuing treatment. Marked elevations (greater than 3-fold ULN) occurred infrequently and reversed with dose reduction or discontinuation of treatment in most cases. However, fatalities associated with severe liver injury have also been reported rarely. A 2009 review of leflunomide adverse event reports by the U.S. Food and Drug Administration identified 49 cases of severe liver injury, including 14 cases of fatal liver failure, between August 2002 and May 2009. An additional five patients required a liver transplant and nine patients experienced a life-threatening event. In this review, concomitant use of other hepatotoxic drugs and preexisting liver disease were associated with the greatest risk for liver injury during leflunomide treatment. Specifically, 46 of the 49 patients were also taking other medications that have been associated with liver injury including methotrexate, TNF-alfa blockers, hydroxychloroquine, paracetamol, nonsteroidal anti-inflammatory drugs and statins, and 14 patients had preexisting liver disease such as active or chronic hepatitis and/or a history of alcohol abuse. The estimated duration of leflunomide exposure before onset of severe liver injury ranged from 9 days to 6 years, with the majority occurring within the first 6 to 12 months of treatment.

Pharmacokinetically, coadministration of leflunomide with rifampin may increase the plasma concentrations of M1, the active metabolite of leflunomide that is responsible for essentially all of its activity in vivo. When a single dose of leflunomide was administered to subjects receiving multiple doses of rifampin, the peak plasma levels of M1 were increased by approximately 40% compared to administration of leflunomide alone. The mechanism has not been described, but may involve rifampin induction of leflunomide metabolism via hepatic CYP450 isoenzymes. Due to the long half-life of M1, levels may continue to increase with multiple dosing of leflunomide.

MANAGEMENT: Caution is advised if leflunomide is used in combination with rifampin. The potential for increased risk of leflunomide toxicities including peripheral neuropathy, immunosuppression, bone marrow suppression, and hepatotoxicity should be considered. Liver enzymes and bilirubin should be measured prior to initiation of leflunomide therapy and at least monthly for the first six months of treatment and every 6 to 8 weeks thereafter. Patients with preexisting liver disease or elevated baseline liver enzymes (i.e., ALT greater than two times ULN) should not receive leflunomide. Patients who develop elevated serum ALT greater than three times ULN while receiving leflunomide should discontinue treatment and be given washout procedures with cholestyramine or activated charcoal to accelerate elimination of leflunomide's active metabolite from plasma, which otherwise may take up to two years. Follow-up monitoring should be conducted at least weekly until the ALT value is within normal range, and washout procedures repeated as necessary. All patients treated with leflunomide should be advised to seek medical attention if they experience potential 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.

Arava

Generic Name: leflunomide

Brand name: Arava

Synonyms: n.a.

What is Arava?

Rifampin Intravenous

Generic Name: rifampin

Brand name: Rifadin, Rifadin IV, Rimactane

Synonyms: Rifampin

What is Rifampin Intravenous?