What are the potential drug interactions between moxifloxacin, cyclosporine, ezetimibe, mycophenolate, rifabutin, resuvastatin, valganciclovir, and septra (sulfamethoxazole/trimethoprim) in a patient?

Drug Interactions in This Multi-Drug Regimen

The most critical interactions in this regimen involve cyclosporine, which significantly increases exposure to both rosuvastatin (7-10 fold) and ezetimibe (2-12 fold), requiring dose reductions of these lipid-lowering agents, and rifabutin, which decreases cyclosporine levels and requires careful monitoring and potential cyclosporine dose adjustments. 1, 2, 3

Critical Cyclosporine-Related Interactions

Cyclosporine + Rosuvastatin

• Rosuvastatin exposure increases 7.1-fold (AUC) and 10.6-fold (Cmax) when coadministered with cyclosporine, primarily through inhibition of hepatic OATP-C transporter-mediated uptake 3
• This combination dramatically increases the risk of myopathy and rhabdomyolysis 1
• Initiate rosuvastatin at the lowest possible dose (5 mg daily maximum) and monitor closely for muscle pain, weakness, or elevated creatine kinase 4
• The interaction is not mitigated by dose timing separation 3

Cyclosporine + Ezetimibe

• Ezetimibe exposure increases 2.3- to 12-fold when combined with cyclosporine, likely through altered glucuronidation 2, 5
• Start ezetimibe at 5 mg daily (half the standard dose) rather than 10 mg, and titrate upward only if needed 5
• Monitor lipid panels every 4-8 weeks initially to assess response and avoid excessive LDL-C reduction 5
• Cyclosporine concentrations should be monitored when ezetimibe is added or removed from the regimen 2

Cyclosporine + Rifabutin

• Rifabutin induces CYP3A4 and P-glycoprotein, significantly decreasing cyclosporine concentrations and risking transplant rejection 1, 4
• Although less potent than rifampin, rifabutin still requires intervention 4
• Increase cyclosporine monitoring frequency to at least weekly when rifabutin is initiated, and anticipate needing to increase cyclosporine doses by 50-100% 1
• Check cyclosporine trough levels 3-4 days after any rifabutin dose change 4

Cyclosporine + Mycophenolate

• No clinically significant pharmacokinetic interaction exists between cyclosporine and mycophenolate 4
• Both are standard components of transplant immunosuppression regimens and can be used together safely 4

Rifabutin-Related Interactions

Rifabutin + Moxifloxacin

• No significant interaction documented between rifabutin and fluoroquinolones including moxifloxacin 6
• Moxifloxacin can be used at standard doses (400 mg daily) without adjustment 6

Rifabutin + Valganciclovir

• No documented pharmacokinetic interaction between rifabutin and valganciclovir 7
• However, monitor for additive myelosuppression (neutropenia, thrombocytopenia) as both agents can cause bone marrow suppression 7
• Obtain complete blood counts every 1-2 weeks during concurrent therapy 7

Septra (Trimethoprim-Sulfamethoxazole) Interactions

Septra + Cyclosporine

• Trimethoprim-sulfamethoxazole can increase cyclosporine nephrotoxicity through additive renal effects 1, 8
• Monitor serum creatinine at least weekly during concurrent use 1
• If creatinine increases by >25% from baseline, reduce or discontinue Septra and consider alternative prophylaxis 1

Septra + Mycophenolate

• No significant pharmacokinetic interaction, but both can cause myelosuppression 8
• Monitor complete blood counts every 1-2 weeks 8

Valganciclovir Interactions

Valganciclovir + Mycophenolate

• Valganciclovir and mycophenolate have no direct pharmacokinetic interaction 4
• Both are commonly used together in transplant recipients for CMV prophylaxis and immunosuppression 4

Monitoring Strategy for This Regimen

Implement the following monitoring schedule:

• Cyclosporine trough levels: Weekly for first month after rifabutin initiation, then every 2 weeks once stable 1
• Serum creatinine: Weekly while on Septra, every 2 weeks otherwise 1
• Complete blood count: Every 1-2 weeks (monitoring for valganciclovir and Septra myelosuppression) 7
• Lipid panel: 4 weeks after initiating ezetimibe or rosuvastatin, then every 8-12 weeks 5
• Creatine kinase: Baseline and if patient reports muscle symptoms 1
• Liver enzymes (ALT/AST): Every 4-8 weeks 2

Critical Pitfalls to Avoid

• Do not use standard doses of rosuvastatin (10-20 mg) with cyclosporine—this dramatically increases rhabdomyolysis risk 3
• Do not assume rifabutin has no effect on cyclosporine simply because it is weaker than rifampin—dose adjustments are still required 4, 1
• Do not separate administration timing to avoid the cyclosporine-rosuvastatin interaction—this does not mitigate the effect 3
• Do not overlook cumulative myelosuppression risk from valganciclovir, Septra, and mycophenolate 7
• Do not fail to educate patients about muscle symptoms (pain, weakness, dark urine) as early warning signs of statin toxicity 1