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Home , Antimycobacterial, Colchicine, Posaconazole, Simvastatin

Major interactions with cyclosporine and

Major drug interactions with cyclosporine (CsA) and tacrolimus (TAC):1,2 éé Increased immunosuppressant concentration êê Decreased immunosuppressant concentration

Interacting class Interacting agents Effect(s) Management suggestions , êê CsA or TAC concentration Closely monitor CsA or TAC serum con- , centration. Effect of CYP3A4 induction , may occur over weeks. , primodone , éé CsA or TAC concentration Closely monitor CsA or TAC serum , concentration. The following empiric (oral), Additive QTc prolongation due initial dose adjustments may be , to fluconazole or considered. voriconazole with TAC For TAC: • decrease dose by 66% if initiating posaconazole or voriconazole, or by 40% if initiating fluconazole ≥ 200 mg/day

For CsA: • decrease dose by 50% if initiating voriconazole, or by 25% if initiating posaconazole or fluconazole ≥ 200 mg/day. Antimalarials Mefloquine, quinine, é CsA or TAC concentration Closely monitor CsA or TAC serum quinidine concentration. Additive QTc prolongation due to tacrolimus with anti- Monitor for QTc prolongation if antima- malarials larial treatment must be initiated in a patient receiving tacrolimus. Antimycobacterial , rifampin êê CsA or TAC concentration Closely monitor CsA or TAC serum concentration. HIV and hepatitis , cobicistat, éé CsA or TAC concentration Closely monitor CsA or TAC serum C virus (HCV) , , concentration. antiretrovirals , indina- CsA may increase protease vir, -, inhibitor concentrations If used with CsA, monitor protease , ritonavir, inhibitor(s) for toxicity and serum , tipranavir concentrations where available. Early consultation with HIV/HCV infectious diseases specialist is recommended. , etravirine, êê CsA or TAC concentration Closely monitor CsA or TAC serum , tipranavir concentration. , eryth- éé CsA or TAC concentration Consider substituting a noninteracting romycin . Azithromycin and spiramycin are less likely to interact.

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BC Provincial Renal Agency • Suite 700-1380 Burrard St. • Vancouver, BC • V6Z 2H3 • 604.875.7340 • BCRenalAgency.ca January 2016

1 of 4 Major drug interactions with cyclosporine and tacrolimus

Other anti-infectives Chloramphenicol, le- é CsA or TAC concentration Closely monitor CsA or TAC serum vofloxacin, metronida- concentration. zole, norfloxacin (with CsA), , tigecycline Antineoplastic Bicalutamide, nilotinib, é CsA or TAC concentration Closely monitor CsA or TAC serum sunitinib, , concentration. vandetanib, vemu- rafenib Antineoplastic agents CsA, and to a lesser degree Monitor antineoplastic for exaggerated that are dependent TAC, may é antineoplastic toxicity and monitor CsA or TAC upon CYP3A4 and/or concentrations. serum concentration when used with P-gp for doxorubicin or vinblastine. (e.g. doxorubicin, Doxorubicin or vinblastine may vinblastine) ê CsA or TAC concentration Crizotinib é CsA or TAC concentration Closely monitor CsA or TAC serum concentration. Increased QTc prolongation with TAC Avoid crizotinib with TAC or monitor for QTc prolongation. Alprazolam, clonaz- é Monitor benzodiazepine effect to deter- epam, , flu- concentration with CsA mine whether dose alteration needed. razepam, midazolam, triazolam Cardiovascular Antiarrhythmics , dronedar- é CsA or TAC concentration Closely monitor CsA or TAC serum one, lidocaine (sys- concentration. temic), quinidine Additive QTc prolongation with TAC Avoid QTc prolonging agents with TAC or closely monitor for QTc prolongation. Apixaban, dabigatran, é concentration Monitor for signs of excessive antico- (direct thrombin rivaroxaban agulation. inhibitors and direct factor Xa inhibitors) Avoid in patients receiving CsA or TAC with renal insufficiency (CrCl < 50 mL/min). Calcium channel Diltiazem, é é CsA or TAC concentra- Closely monitor CsA or TAC serum blockers (CCB) tion concentration. , , é é TAC concentration Closely monitor TAC serum concentra- tion. Amlodipine, felodipine, é dihydropyridine CCB con- Monitor for exaggerated dihydropyridine nifedipine, nimodipine centration with CsA CCB effects.

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BC Provincial Renal Agency • Suite 700-1380 Burrard St. • Vancouver, BC • V6Z 2H3 • 604.875.7340 • BCRenalAgency.ca January 2016

2 of 4 Major drug interactions with cyclosporine and tacrolimus

HMG-CoA reductase , , é concentration and Avoid . inhibitors (“”) , rosuvas- risk of statin toxicity including and pravastatin may have a tatin, simvastatin myotoxicity with CsA lower risk of interaction.

TAC does not appear to alter Avoid using maximum doses of statins atorvastatin concentrations as the statin levels are likely in one pK study. There is one higher than expected from the dose. case report associating TAC and simvastatin usage with . Other cardiovascular , dipyri- é CsA or TAC concentration Closely monitor CsA or TAC serum damole, propranolol, concentration. TAC is less likely to be altered than CsA. Dietary juice and é CsA or TAC concentration Avoid grapefruit juice and grapefruit with grapefruit CsA or TAC. Gastrointestinal , cimetidine, é CsA or TAC concentration Closely monitor CsA or TAC serum concentration Metoclopramide é CsA or TAC concentration Octreotide é CsA (orally administered) CsA microemulsion may be less likely to interact with octreotide. Additive QTc prolongation with TAC êê CsA concentration Closely monitor CsA serum concentra- tion , lansopra- é TAC concentration Pantoprazole and rabeprazole are less zole likely to interact. and anti- Anti-gout éé CsA concentration. The Closely monitor CsA serum concentra- mechanism is unknown. tion Colchicine é colchicine toxicity. Monitor for toxicity and consider dose reduction if co-administration is un- Toxic effects more pro- avoidable. nounced with renal and/or hepatic insufficiency. For patients with normal renal and hepatic function, the following dose reductions are suggested: acute gout: 0.6 mg once followed by 0.3 mg one hour later. Do not repeat before 72 hours. Gout prophylaxis: reduce dose by 50%; double interval. Herbs St. Johns wort êê CsA or TAC concentration Avoid St. John's wort with CsA or TAC. Schisandra é TAC concentration Avoid Schisandra with CsA or TAC. Hormones Estrogen preparations é CsA concentration Closely monitor CsA serum concentra- tion Testosterone prepa- é CsA or TAC concentration Closely monitor CsA or TAC serum rations (including concentration if concurrent use cannot , methyltestos- be avoided. terone, testosterone)

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BC Provincial Renal Agency • Suite 700-1380 Burrard St. • Vancouver, BC • V6Z 2H3 • 604.875.7340 • BCRenalAgency.ca January 2016

3 of 4 Major drug interactions with cyclosporine and tacrolimus

Hypnotic (also see zopiclone, zolpidem é in concentration Monitor hypnotic effect to determine benzodiazepines with CsA whether dose alteration is needed. above) Hypoglycemic Sulfonylureas including é CsA concentration Monitor CsA concentrations closely. gliclazide, glimepiride, glyburide Immunosuppres- Cyclosporine (CsA) Increased risk of serious Alteration of mycophenolate dosing is sant renal, hematologic, and other usually required when CsA is initiated, toxicities in combination with stopped, or added. When used with everolimus, reduction êê mycophenolate concen- of CsA dose and target concentration is tration generally necessary.

éé everolimus concentration It is suggested that oral doses of siro- limus be administered four hours after éé sirolimus (with cyclospo- cyclosporine doses. rine microemulsion) Tacrolimus (TAC) Increased risk of serious renal, Avoid concomitant use with sirolimus. hematologic, or other toxicities with sirolimus If everolimus is used with TAC, closely monitor everolimus serum concentra- é everolimus concentration tions. Psychiatry Desipramine, halo- é CsA or TAC concentration Consider that do not peridol, fluoxetine, interact; closely monitor CsA or TAC fluvoxamine, sertraline, serum concentration if used. Pimozide Elevated pimozide level and/or Avoid use of pimozide due to increased increased QTc prolongation risk of cardiotoxicity.

Other êê CsA or TAC concentration Closely monitor CsA or TAC serum concentration.

Cinacalcet ê CsA or TAC concentration

Sevelamer ê TAC concentration

êê CsA concentration

References

1. Major drug interactions with immunosuppressants: Lexi-interact 1978-2016 2. Baxter K, Baxter P, Claire, L. Immunosuppressant monograph: Stockley’s drug interactions 10th ed. 2013

BC Provincial Renal Agency • Suite 700-1380 Burrard St. • Vancouver, BC • V6Z 2H3 • 604.875.7340 • BCRenalAgency.ca January 2016

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