Can ramipril (Angiotensin-Converting Enzyme (ACE) inhibitor) cause Creatine Phosphokinase (CPK) elevation in a patient with known Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency?

Ramipril and CPK Elevation in G6PD Deficiency

There is no evidence that ramipril causes CPK elevation in patients with G6PD deficiency, and ACE inhibitors like ramipril are actually preferred antihypertensive agents in patients with G6PD deficiency due to their kidney-protective effects.

Relationship Between Ramipril and G6PD Deficiency

ACE inhibitors like ramipril are not contraindicated in G6PD deficiency and do not appear on lists of medications that cause hemolysis in these patients. The current evidence suggests:

• ACE inhibitors are not among medications that cause hemolytic anemia in G6PD-deficient patients 1
• In fact, ACE inhibitors are recommended in patients with residual kidney function who have G6PD deficiency 2
• A comprehensive review of medications contraindicated in G6PD deficiency does not include ramipril or other ACE inhibitors 3

CPK Elevation and G6PD Deficiency

CPK (Creatine Phosphokinase) elevation is typically associated with:

1. Muscle damage/rhabdomyolysis
2. Myocardial infarction
3. Certain medications that directly affect muscle tissue

G6PD deficiency primarily affects red blood cells, not muscle tissue. The primary concern with G6PD deficiency is hemolytic anemia, not muscle damage that would lead to CPK elevation.

Medications Truly Contraindicated in G6PD Deficiency

The medications with solid evidence showing they should be avoided in G6PD deficiency include:

• Dapsone
• Methylthioninium chloride (methylene blue)
• Nitrofurantoin
• Phenazopyridine
• Primaquine
• Rasburicase (specifically contraindicated) 2
• Tolonium chloride (toluidine blue) 1

Benefits of ACE Inhibitors in Patients with G6PD Deficiency

ACE inhibitors like ramipril may actually be beneficial in patients with G6PD deficiency who require antihypertensive medication:

• ACE inhibitors help preserve residual kidney function in patients with kidney disease 2
• In a study of peritoneal dialysis patients, those receiving ramipril had almost 1 mL/min greater glomerular filtration rate after one year compared to those not receiving the drug 2
• ACE inhibitors have been shown to reduce cardiovascular events in patients with chronic kidney disease 2

Clinical Approach to Patients with G6PD Deficiency

When treating patients with G6PD deficiency:

1. Avoid the seven medications with solid evidence of causing hemolysis (listed above)
2. Monitor for signs of hemolysis (jaundice, dark urine, fatigue, back/abdominal pain)
3. Consider ACE inhibitors like ramipril as preferred agents when antihypertensive therapy is needed

Monitoring Recommendations

While ramipril is not expected to cause CPK elevation in G6PD-deficient patients, prudent monitoring might include:

• Baseline CPK measurement before starting therapy
• Follow-up CPK if the patient reports muscle pain or weakness
• Regular monitoring of renal function, as is standard with ACE inhibitor therapy
• Monitoring for signs of hemolysis during any new medication initiation in G6PD-deficient patients

Real-World Evidence

A real-world study of over 31,000 G6PD-deficient patients found that many medications previously suspected of causing hemolysis were actually prescribed safely to these patients 4. This further supports that ACE inhibitors like ramipril can be used safely in this population.

In conclusion, there is no evidence suggesting ramipril causes CPK elevation specifically in G6PD-deficient patients, and ACE inhibitors are actually preferred agents in this population when antihypertensive therapy is needed.