Interaction between Leflunomide and Rosuvastatin
Major
Synergy
Metabolism
| ID | DDInter1033 and DDInter1622 |
| Interaction |
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. Coadministration with teriflunomide may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of the organic anion transporting polypeptide (OATP) 1B1 and 1B3 and/or breast cancer resistance protein (BCRP) transporters. The proposed mechanism, based on in vivo data, is decreased clearance due to teriflunomide-mediated inhibition of OATP 1B1/1B3 or BCRP transport proteins.
abdominal pain
alopecia
Amnesia
anaemia
Aching joints
Arthritis rheumatoid
blepharoptosis
bronchitis
cognitive disorder
confusion
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| Management | Caution is advised if leflunomide or teriflunomide must be used in patients who are currently receiving or have recently received treatment with other hepatotoxic agents or are receiving drugs that are substrates of OATP 1B1/1B3 and/or BCRP, such as rosuvastatin. Liver enzymes and bilirubin should be measured prior to initiation of leflunomide/teriflunomide 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 or teriflunomide. Patients who develop elevated serum ALT greater than three times ULN while receiving these medications 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 or teriflunomide 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. If concomitant administration is required, the dose of rosuvastatin should not exceed 10 mg once daily. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever leflunomide or teriflunomide is added to or withdrawn from therapy with rosuvastatin. |
| References | |
| Alternative for Leflunomide |
L04A
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| Alternative for Rosuvastatin |
C10A
A10B
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.