What are the risks and considerations for combining Lisinopril (Angiotensin-Converting Enzyme Inhibitor) with Prednisone (Corticosteroid) and Rinvoq (Upadacitinib) in a patient with hypertension and ulcerative colitis?

Combining Lisinopril with Prednisone and Rinvoq in Hypertension for Ulcerative Colitis

This triple-drug combination is feasible but requires intensive monitoring for hypertension exacerbation, infection risk, and thrombotic events—lisinopril should be continued for cardiovascular protection while prednisone must be tapered rapidly and Rinvoq requires specific safety surveillance per FDA guidelines. 1

Critical Safety Considerations

Hypertension Management with This Combination

• Prednisone significantly worsens hypertension through sodium retention and volume expansion, requiring close blood pressure monitoring during the corticosteroid course 2
• Lisinopril should be continued as ACE inhibitors provide essential cardiovascular protection in patients with hypertension, and there is no contraindication to combining it with prednisone or upadacitinib 3
• Monitor blood pressure weekly at home for the first month after initiating Rinvoq, then every 6 months thereafter, as recommended for patients with pre-existing hypertension on upadacitinib 2
• The combination of lisinopril with beta-blockers has been studied and shows additive blood pressure lowering without significant safety concerns, suggesting ACE inhibitors are safe in multi-drug regimens 3

Infection Risk with Triple Immunosuppression

The most critical concern is the compounded infection risk from combining corticosteroids with Rinvoq (upadacitinib). 1

• The FDA black box warning for Rinvoq explicitly states that patients taking concomitant immunosuppressants such as corticosteroids are at increased risk for serious infections that may lead to hospitalization or death 1
• This includes tuberculosis, invasive fungal infections (cryptococcosis, pneumocystosis), bacterial, viral (including herpes zoster), and opportunistic infections 1
• Prior to initiating Rinvoq, evaluate for active and latent tuberculosis—if positive, treat TB before starting upadacitinib 1
• Screen for viral hepatitis and do not initiate Rinvoq in patients with active hepatitis B or C 1
• Monitor closely for signs and symptoms of infection during and after treatment, including development of TB in patients who initially tested negative 1

Corticosteroid Strategy in This Context

Prednisone should only be used for short-term induction and must not be continued for maintenance. 2

• The 2025 British Society of Gastroenterology guidelines explicitly state that corticosteroids are not recommended for long-term maintenance in ulcerative colitis 2
• Prednisolone 40 mg/day is the optimal dose for moderate-to-severe UC, with no additional benefit from higher doses (40-60 mg/day) but increased adverse effects 2
• Taper gradually over 6-8 weeks once clinical improvement occurs to minimize adverse effects 2
• If there is no adequate response to oral corticosteroids within 2 weeks, advanced therapy (like Rinvoq) should be started rather than prolonging steroid exposure 2

Rinvoq-Specific Monitoring Requirements

The FDA label mandates specific baseline evaluations and ongoing monitoring: 1

• Baseline complete blood count—do not initiate if absolute lymphocyte count <500 cells/mm³, absolute neutrophil count <1,000 cells/mm³, or hemoglobin <8 g/dL 1
• Assess lymphocyte count every 3 months during treatment 2
• Liver function testing at 1 month after initiation, then every 3 months 2
• Monitor for thrombotic events—the FDA warns of deep venous thrombosis, pulmonary embolism, and arterial thrombosis with JAK inhibitors, particularly in patients ≥50 years with cardiovascular risk factors 1

Cardiovascular and Thrombotic Risk

Patients ≥50 years with cardiovascular risk factors face heightened risks with this combination. 1

• The FDA black box warning notes higher rates of major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction, and stroke with JAK inhibitors compared to TNF blockers in at-risk populations 1
• Higher rates of all-cause mortality were observed with JAK inhibitors in RA patients ≥50 years with cardiovascular risk factors 1
• Discontinue Rinvoq immediately if the patient experiences myocardial infarction or stroke 1
• Current or past smokers are at additional increased risk for both malignancy and cardiovascular events 1

Practical Management Algorithm

Step 1: Pre-Treatment Assessment

• Verify hypertension is controlled on current lisinopril dose
• Complete baseline labs: CBC with differential, liver enzymes, TB testing, viral hepatitis screening 1
• Assess cardiovascular risk factors and smoking history 1
• Ensure no active infections 1

Step 2: Initiation Strategy

• Continue lisinopril at current dose for cardiovascular protection
• Start prednisone 40 mg daily for UC flare (not higher doses) 2
• Initiate Rinvoq per FDA dosing guidelines for ulcerative colitis 1
• Educate patient on infection symptoms and thrombosis warning signs 1

Step 3: Intensive Monitoring Phase (First 3 Months)

• Weekly home blood pressure monitoring for first month, then as clinically indicated 2
• Assess for infection symptoms at every contact 1
• CBC at 1 and 3 months, then every 3 months 2, 1
• Liver function at 1 month, then every 3 months 2
• Begin prednisone taper once clinical improvement occurs, completing over 6-8 weeks 2

Step 4: Long-Term Maintenance

• Discontinue prednisone completely—do not use for maintenance 2
• Continue Rinvoq as the maintenance agent if successful in achieving remission 2
• Maintain lisinopril for hypertension control
• Monitor blood pressure every 6 months 2
• Continue quarterly CBC and liver function monitoring 2

Critical Pitfalls to Avoid

• Do not prolong prednisone beyond 2-3 weeks without response—this increases complication risk without improving outcomes 4
• Do not use Rinvoq in combination with other potent immunosuppressants like azathioprine or cyclosporine per FDA limitations 1
• Do not ignore new infection symptoms—interrupt Rinvoq until infection is controlled 1
• Do not continue Rinvoq if thrombotic event occurs—promptly evaluate and discontinue 1
• Do not assume blood pressure will remain stable—both prednisone and Rinvoq can affect blood pressure, requiring lisinopril dose adjustment 2

Special Considerations for Acute Severe UC

If this patient has acute severe ulcerative colitis (ASUC) requiring hospitalization:

• Intravenous methylprednisolone 40-60 mg/day is preferred over oral prednisone for severe disease meeting Truelove and Witts criteria 4
• Emerging data suggest upadacitinib with IV corticosteroids may be effective in ASUC, with 76% avoiding colectomy at 90 days in one multicenter series 5
• Consider colectomy if no response to medical therapy within 5-7 days to avoid fatal opportunistic infections from prolonged triple immunosuppression 6, 7
• The 24% colectomy rate with upadacitinib in ASUC is comparable to historical cyclosporine data 5