This afternoon I met a perscription that consist of nine different agents, which have twenty drug interactions. Many of them are cardiovascular drugs. They are Beta-Blockers, Electrolytes, Statins, ARBs, Inotropic Agents, Thiazide, Calcium Channel Blockers, and Benzodiazepines. I list them and their dosage below.
- Alprazolam 0.4 mg po Qd
- Metoprolol 12.5 mg po Bid
- Potassium Chloride 1 g po Bid
- Simvastatin 20 mg po Qn
- Irbesartan 0.15 g po Qd
- Irbesartan/Hydrochlorothiazide 1 tablet po Qd
- Digoxin 0.125 mg po Qd
- Amlodipine 5 mg po Qd
- Warfarin 2.5 mg po Qd
I check these nine drug in Multi-Dug Interaction Chechker and find there are twenty drug interactions between these nine drugs. They are:
Serious – Use alternative
Amlodipine + Simvastatin. Amlodipine increases levels of simvastatin by Other (See comment). Possible serious or life-threatening interaction. Monitor closely. Use alternatives if available. Comment: Benefits of combination therapy should be carefully weighed against the potential risks of combination. Potential for increased risk of myopathy/rhabdomyolysis. Limit simvastatin dose to no more than 20 mg/day when used concurrently.
Significant – Monitor Closely
Hydrochlorothiazide + Digoxin. Hydrochlorothiazide increases effects of digoxin by pharmacodynamic synergism. Significant interaction possible, monitor closely. Hypokalemia increases digoxin effects.
Potassium Chloride + Hydrochlorothiazide. Potassium chloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Potential for dangerous interaction. Use with caution and monitor closely.
Simvastatin + Warfarin. Simvastatin, warfarin. Either increases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Significant – Monitor Closely. Competition by each drug for CYP3A4-mediated metabolism may result in increased INR and increased risk of rhabdomyolysis.
Simvastatin + Digoxin. Simvastatin will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Significant – Monitor Closely.
Digoxin + Hydrochlorothiazide. Digoxin will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Significant – Monitor Closely.
Metoprolol + Irbesartan. Metoprolol, irbesartan. Mechanism: pharmacodynamic synergism. Significant – Monitor Closely. Risk of fetal compromise if given during pregnancy.
Alprazolam + Digoxin. Alprazolam increases levels of digoxin by unknown mechanism. Significant – Monitor Closely.
Metoprolol + Digoxin. Metoprolol increases effects of digoxin by pharmacodynamic synergism. Significant – Monitor Closely. Enhanced bradycardia.
Metoprolol + Amlodipine. Metoprolol and amlodipine both increase anti-hypertensive channel blocking. Significant – Monitor Closely.
Irbesartan + Potassium Chloride. Irbesartan and potassium chloride both increase serum potassium. Significant – Monitor Closely.
Metoprolol + Potassium Chloride. Metoprolol and potassium chloride both increase serum potassium. Significant – Monitor Closely.
Potassium Chloride + Digoxin. Potassium chloride and digoxin both increase serum potassium. Significant – Monitor Closely.
Irbesartan + Metoprolol. Irbesartan and metoprolol both increase serum potassium. Significant – Monitor Closely.
Irbesartan + Digoxin. Irbesartan and digoxin both increase serum potassium. Significant – Monitor Closely.
Irbesartan + Hydrochlorothiazide. Irbesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Significant – Monitor Closely.
Metoprolol + Digoxin. Metoprolol and digoxin both increase serum potassium. Significant – Monitor Closely.
Metoprolol + Hydrochlorothiazide. Metoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Significant – Monitor Closely.
Digoxin + Hydrochlorothiazide. Digoxin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Significant – Monitor Closely.
Irbesartan + Irbesartan/Hydrochlorothiazide (Not listed in the multi-drug interaction checker. I add this interaction by myself). Both Irbesartan and Irbesartan/Hydrochlorothiazide increase the level or effects of each other. The combination use of these two drugs is repeated administration and may enhance adverse effects of Irbesartan. I think this combination use should be avoid absolutely.
I alysis these twenty drug interactions. These twenty drug interactions include ten refered to potassium disorder, three refered to pharmacodynamic synergism, one refered to myopathy/rhabdomyolysis, one hepatic/instestinal enzyme, one MDR1 (P-gp), one renal tubular excretion, one unknown, one anti-hypertension channel, and one repeated administration.
I think the next thing to do is to modify this pharmacotherapy regimen as there are many drug interactions in this regimen.