Does cyclosporine (CsA) cause hypertension (HTN)?

Cyclosporine Causes Hypertension in Approximately 20% of Patients

Yes, cyclosporine definitely causes hypertension in approximately 20% of patients, with the hypertension generally improving when the medication is discontinued. 1

Mechanism of Cyclosporine-Induced Hypertension

• The pathogenesis is thought to be primarily due to a vasoconstrictive effect on vascular smooth muscle, particularly in the kidney 1
• Research in transplant recipients has confirmed cyclosporine-induced nitric oxide (NO) system upregulation, with possible cyclosporine-induced production of superoxide leading to NO destruction, inducing vasoconstriction and hypertension 1
• The hypertensive effects result from renal arteriole vasoconstriction, which is why calcium channel blockers are often the antihypertensive of choice 1

Risk Factors and Clinical Presentation

• Hypertension can develop at any time during treatment with cyclosporine 1
• It is more commonly seen in patients over 45 years of age 1
• Patients with pre-existing or borderline hypertension are at greater risk 1
• In transplant patients, hypertension occurs in approximately 50% of renal transplant recipients and most cardiac transplant patients 2

Management of Cyclosporine-Induced Hypertension

• The development of hypertension does not automatically necessitate cessation of cyclosporine therapy 1

• Management options include:

  • Reducing the cyclosporine dosage if hypertension occurs 1, 2
  • Treating the hypertension with appropriate medications 1
  • Discontinuing cyclosporine if a satisfactory blood pressure cannot be maintained 1

• According to FDA labeling, if hypertension occurs, the dose of cyclosporine should be decreased by 25% to 50% 2

• If hypertension persists despite dose reduction, blood pressure should be controlled with anti-hypertensive agents 2

Preferred Antihypertensive Medications

• Calcium channel blockers are the preferred antihypertensive agents due to their ability to relax vascular smooth muscles 1

• Recommended calcium channel blockers include:

  • Nifedipine, isradipine, felodipine, or amlodipine 1
  • These agents do not interact with cyclosporine metabolism and are also nephroprotective 1
  • Isradipine specifically does not interact with cyclosporine metabolism 1

• β-Blockers can also be used for blood pressure control 1

• Avoid:

  • Verapamil and diltiazem as they inhibit cyclosporine metabolism (unless cyclosporine blood levels can be monitored) 1
  • Thiazide diuretics as they enhance nephrotoxicity 1
  • Potassium-sparing diuretics as cyclosporine can induce hyperkalemia 1

Monitoring Recommendations

• Regular blood pressure monitoring is essential 1, 2
• Early morning resting blood pressure is a more sensitive indicator of early nephrotoxicity than elevated creatinine 1
• If hypertension is observed on 2 separate occasions, the dose of cyclosporine should be decreased 1
• In psoriasis patients, biweekly early morning blood pressure checks over the first 6-8 weeks and then monthly monitoring if no persistent abnormalities are identified 1

Important Caveats

• Calcium channel blockers have the disadvantage of inducing gingival hyperplasia, possibly adding to this effect of cyclosporine 1
• Hypertension is a contraindication to initiating cyclosporine therapy 1
• In clinical trials, systolic hypertension (defined as two systolic blood pressure readings >140 mm Hg) and diastolic hypertension (defined as two diastolic blood pressure readings >90 mm Hg) occurred in 33% and 19% of rheumatoid arthritis patients treated with cyclosporine, respectively 2
• Hypertension generally improves when cyclosporine is discontinued 1, 2