Is rash or eczematous dermatitis a known adverse effect of amlodipine?

Is Skin Rash or Eczema a Side Effect of Amlodipine?

Yes, skin rash and eczematous dermatitis are recognized adverse effects of amlodipine, occurring in approximately 1-2% of patients, with rash specifically listed in the FDA prescribing information as a documented side effect. 1

FDA-Documented Dermatologic Adverse Effects

The FDA label for amlodipine explicitly lists several cutaneous reactions that occurred in clinical trials:

• Rash (including erythematous and maculopapular variants) occurred in <1% but >0.1% of patients in controlled trials, with incidence between 1-2% across all multiple-dose studies 1
• Pruritus (itching) was documented as an adverse reaction 1
• Angioedema and erythema multiforme were reported in post-marketing surveillance 1
• Allergic reactions were documented among general adverse effects 1

Clinical Patterns of Amlodipine-Induced Skin Reactions

Common Presentations

• Maculopapular rash is the most frequent dermatologic manifestation (41.7% of cutaneous reactions to calcium channel blockers), typically presenting as a pruritic, erythematous eruption 2
• The rash characteristically develops after a latency period, with one documented case showing onset on day 12 of therapy 3
• Eczematous dermatitis has been reported, though less commonly than maculopapular patterns 4

Severe Cutaneous Reactions (Rare but Critical)

While uncommon, amlodipine can trigger life-threatening dermatologic emergencies:

• Stevens-Johnson syndrome has been documented in 3 patients (6.2% of those with cutaneous reactions) 2
• Toxic epidermal necrolysis with 48.5% body surface area involvement and conjunctival sloughing has been reported, with a SCORTEN score of 4 predicting 58% mortality 3
• Linear IgA disease presenting as large erythematous plaques with vesicles has been documented 5

Diagnostic Confirmation

When amlodipine-induced dermatitis is suspected:

• Lymphocyte transformation testing (LTT) can confirm drug causality, with the first reported positive LTT for amlodipine demonstrating cross-reactivity with nifedipine 4
• Skin biopsy may show subepidermal blisters with neutrophils and eosinophils in severe cases 5
• Direct immunofluorescence can identify IgA deposition along the basement membrane in linear IgA disease 5
• The Naranjo assessment can be used to establish causality (score of 5 indicates probable drug-induced reaction) 3

Management Algorithm

Mild Reactions (Localized Rash, <10% BSA)

1. Continue amlodipine if blood pressure control is critical and rash is tolerable
2. Apply moderate-potency topical corticosteroids (e.g., mometasone 0.1% or betamethasone 0.1%) to affected areas 6
3. Use non-sedating antihistamines (e.g., loratadine 10 mg daily) for daytime pruritus 6
4. Consider sedating antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) at bedtime for nighttime itching 7
5. Apply emollients at least once daily to prevent skin dryness 6

Moderate Reactions (Widespread Rash, 10-30% BSA, or Significant Pruritus)

1. Discontinue amlodipine immediately 3, 5
2. Initiate high-potency topical corticosteroids 7
3. Add oral antihistamines for symptom control 7
4. Monitor for progression over 48-72 hours
5. Switch to an alternative antihypertensive class (ACE inhibitor, ARB, or beta-blocker) rather than another calcium channel blocker due to potential cross-reactivity 4

Severe Reactions (>30% BSA, Blistering, Mucosal Involvement, or Systemic Symptoms)

1. Discontinue amlodipine permanently 3, 5
2. Urgent dermatology consultation within 24 hours 7
3. Assess for DRESS syndrome criteria: fever >38°C, eosinophilia >700/μL, lymphadenopathy, organ involvement (ALT >2× ULN, creatinine >1.5× baseline) 7, 8
4. If DRESS is suspected:
   • Start IV methylprednisolone 1-2 mg/kg/day 7
   • Plan for minimum 4-week steroid taper to prevent relapse 7
   • Obtain CBC with differential, comprehensive metabolic panel, and urinalysis 7
5. If Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected:
   • Immediate transfer to burn unit or ICU 7
   • Initiate systemic immunosuppressive therapy 9
   • Consider IVIG 1-2 g/kg for refractory cases 7

Critical Pitfalls to Avoid

• Do not rechallenge with amlodipine after a confirmed hypersensitivity reaction, as this can trigger more severe reactions 4, 3
• Avoid switching to nifedipine or other dihydropyridine calcium channel blockers, as cross-reactivity has been documented via positive LTT 4
• Do not use prophylactic corticosteroids or antihistamines when initiating amlodipine therapy, as this may mask early warning signs of severe reactions 6
• Do not perform patch testing or delayed intradermal testing until at least 6 months after complete resolution and at least 4 weeks after discontinuing systemic steroids (>10 mg prednisone-equivalent) 7, 8

Risk Stratification

• Diltiazem shows the highest rate of cutaneous reactions per million prescriptions among calcium channel blockers, suggesting amlodipine may have a relatively lower risk profile within this drug class 2
• Female patients may have higher incidence of certain adverse effects with amlodipine, though this has not been specifically quantified for dermatologic reactions 1
• Patients with renal or cardiovascular involvement (8.7% of those with cutaneous reactions) require closer monitoring 2