What high blood pressure medication would you prescribe for a patient taking 45mg of Rinvoq (upadacitinib) once daily and 35mg of Prednisone once daily?

Antihypertensive Selection for Patients on Rinvoq and Prednisone

Direct Recommendation

Start with a calcium channel blocker (amlodipine 5-10mg daily) as first-line therapy, as it provides effective blood pressure control without significant drug interactions with upadacitinib or prednisone, and can be easily combined with an ACE inhibitor or ARB plus a thiazide diuretic if additional agents are needed. 1

Rationale for Calcium Channel Blocker First-Line

• Amlodipine is weight-neutral and does not adversely affect glucose or lipid metabolism, which is particularly important given that prednisone 35mg daily significantly increases risk of hyperglycemia, weight gain, and metabolic dysfunction 1

• Calcium channel blockers provide smooth 24-hour blood pressure control with once-daily dosing and are well tolerated as monotherapy, with mean blood pressure reductions of 23/13 mmHg demonstrated in clinical trials 2

• There are no significant drug-drug interactions between amlodipine and either upadacitinib (Rinvoq) or prednisone, making it a safe initial choice 1

Stepwise Escalation Algorithm if Monotherapy Insufficient

Second Agent: Add ACE Inhibitor or ARB

• If blood pressure remains ≥140/90 mmHg on amlodipine alone, add lisinopril 10-20mg daily or losartan 50-100mg daily to achieve guideline-recommended dual therapy 1

• The combination of amlodipine with an ACE inhibitor provides complementary mechanisms—vasodilation through calcium channel blockade and renin-angiotensin system inhibition—with superior blood pressure control compared to either agent alone 1, 3

• This combination is particularly beneficial for patients with chronic kidney disease, heart failure, or coronary artery disease, and may attenuate peripheral edema that can occur with amlodipine monotherapy 1

Third Agent: Add Thiazide-Like Diuretic

• If blood pressure remains uncontrolled on amlodipine plus ACE inhibitor/ARB, add chlorthalidone 12.5-25mg daily or hydrochlorothiazide 25mg daily to achieve guideline-recommended triple therapy 1

• The combination of ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic represents the evidence-based triple therapy targeting three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction 1

• Chlorthalidone is preferred over hydrochlorothiazide due to its longer duration of action and superior cardiovascular outcomes data 1

Critical Monitoring Considerations

Metabolic Effects of Prednisone

• Monitor fasting glucose and HbA1c closely, as prednisone 35mg daily substantially increases diabetes risk, and thiazide diuretics can worsen glucose intolerance 1

• Monitor serum potassium 2-4 weeks after initiating ACE inhibitor/ARB or thiazide diuretic therapy, as prednisone can cause hypokalemia while ACE inhibitors/ARBs increase hyperkalemia risk 1

• Check serum creatinine to detect acute kidney injury, particularly when combining ACE inhibitors/ARBs with diuretics 1

Blood Pressure Targets

• Target blood pressure should be <140/90 mmHg minimum for most patients, with <130/80 mmHg ideal for higher-risk patients 1

• Reassess blood pressure within 2-4 weeks after any medication adjustment, with the goal of achieving target blood pressure within 3 months 1

Important Caveats and Pitfalls to Avoid

Drug Interactions to Consider

• Avoid NSAIDs, as they significantly interfere with blood pressure control and should be withdrawn if possible, particularly important given the patient is already on prednisone which increases cardiovascular risk 1

• Verify medication adherence before escalating therapy, as non-adherence is the most common cause of apparent treatment resistance 1

Combination Therapy Errors

• Do not combine an ACE inhibitor with an ARB, as dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 1

• Avoid beta-blockers as second or third-line agents unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction), as they are less effective than the recommended combinations and can worsen metabolic parameters 1

Resistant Hypertension Management

• If blood pressure remains uncontrolled despite triple therapy (amlodipine + ACE inhibitor/ARB + thiazide diuretic) at optimal doses, add spironolactone 25-50mg daily as the preferred fourth-line agent 1

• Monitor potassium closely when adding spironolactone to an ACE inhibitor/ARB, as hyperkalemia risk is significant 1

• Consider referral to a hypertension specialist if blood pressure remains ≥160/100 mmHg despite four-drug therapy at optimal doses 1

Preference for Single-Pill Combinations

• Fixed-dose single-pill combinations significantly improve medication adherence and persistence compared to separate pills, and should be strongly preferred when using combination therapy 4, 5

• Single-pill combinations of perindopril/amlodipine or lisinopril/amlodipine have demonstrated excellent treatment adherence rates (94%) and effective blood pressure control (66-68% achieving target) in real-world clinical practice 5