Can any of the patient's current medications, including Atenolol (beta blocker), buPROPion (bupropion) ER, Cefdinir (antibiotic), Folic Acid, Gabapentin (anticonvulsant), Lisinopril (ACE inhibitor), LORazepam (benzodiazepine), Methotrexate (immunosuppressant), Mounjaro (tirzepatide), Propranolol (beta blocker), and Testosterone Cypionate (anabolic steroid), increase the risk of Stevens-Johnson Syndrome (SJS) in a patient with a complex medical history, including hypertension, heart failure, rheumatoid arthritis, anxiety, and possible megaloblastic anemia and hypogonadism?

Stevens-Johnson Syndrome Risk Assessment for Current Medications

Among this patient's medications, cefdinir (antibiotic), bupropion, and methotrexate carry documented risk for Stevens-Johnson Syndrome (SJS), with cefdinir posing the highest immediate concern as a cephalosporin antibiotic. 1

High-Risk Medications in This Regimen

Cefdinir (Cephalosporin Antibiotic)

• Cephalosporins carry a multivariate relative risk of 14 (95% CI: 3.2 to 59) for SJS/toxic epidermal necrolysis (TEN). 1
• The risk is highest during short-term use, which matches this patient's 7-day course. 1
• This represents one of the most significant SJS risks in the current medication list. 1

Bupropion ER

• Bupropion has documented case reports of inducing SJS, though it remains a rare adverse effect. 2
• The U.S. prescribing information lists SJS as a potential side effect. 2
• Critical consideration: This patient is on chronic bupropion therapy, and SJS risk with long-term medications is highest in the first 2 months of treatment. 1
• If this patient has been on bupropion beyond 2 months, current risk is substantially lower. 1

Methotrexate

• Methotrexate can cause "severe, occasionally fatal, skin reactions" following single or multiple doses. 3
• Reactions have occurred within days of administration via any route (oral, IM, IV, intrathecal). 3
• The FDA label specifically warns about severe skin reactions, though SJS is not explicitly named. 3
• Recovery has been reported with discontinuation of therapy. 3

Medications with Minimal to No SJS Risk

Beta-Blockers (Atenolol, Propranolol)

• No significant association between beta-blockers and SJS has been established in large case-control studies. 1
• These medications are not listed among drugs causing increased SJS risk. 1

ACE Inhibitors (Lisinopril)

• Lisinopril and other ACE inhibitors show no significant increase in SJS risk. 1
• Large surveillance studies did not identify ACE inhibitors as SJS-associated medications. 1

Benzodiazepines (Lorazepam)

• Benzodiazepines are not associated with increased SJS risk in epidemiologic studies. 1

Other Medications

• Gabapentin, folic acid, testosterone cypionate, and tirzepatide (Mounjaro) have no established association with SJS. 1
• These medications were not identified as risk factors in comprehensive case-control surveillance. 1

Critical Clinical Pitfalls

Timing Considerations

• For medications used chronically (bupropion, methotrexate, gabapentin, cardiovascular drugs), SJS risk is concentrated in the first 2 months of therapy. 1
• If this patient has been stable on these medications for >2 months, the risk is substantially lower. 1
• Cefdinir poses immediate risk as a newly initiated short-course antibiotic. 1

Drug Interactions Increasing Methotrexate Toxicity

• This patient is on multiple medications that can increase methotrexate toxicity, potentially increasing skin reaction risk: 4, 3
  • NSAIDs (if taken) reduce renal elimination of methotrexate 4, 3
  • Renal impairment (monitor given hypertension/heart failure) significantly increases toxicity risk 4, 3
  • Advanced age increases methotrexate toxicity risk 4, 3

Warning Signs Requiring Immediate Action

• Discontinue cefdinir, bupropion, or methotrexate immediately if the patient develops: 3, 1
  • Mucosal involvement (oral, ocular, genital lesions)
  • Painful skin lesions with epidermal detachment
  • Target-like or purpuric skin lesions
  • Fever with rash
  • Conjunctivitis or photophobia

Polypharmacy Context

• This patient is taking 11 medications, placing them at increased risk for adverse drug events. 5
• Patients taking ≥5 medications average 1 significant drug problem. 5
• The prescribing cascade and multiple comorbidities increase complexity and risk. 5

Risk Mitigation Strategy

If SJS concern arises, prioritize discontinuation in this order: 1, 3

1. Cefdinir (highest acute risk as cephalosporin antibiotic) 1
2. Methotrexate (FDA-documented severe skin reactions) 3
3. Bupropion (documented SJS cases, though rare) 2

Monitor closely during the 7-day cefdinir course and for 1-2 weeks after completion, as this represents the highest-risk period. 1