What are the current indications, recommended dosing regimens, contraindications, and major adverse effects of quinacrine (mepacrine) for refractory cutaneous lupus erythematosus and giardiasis?

Quinacrine (Mepacrine) for Refractory Cutaneous Lupus Erythematosus

Quinacrine should be considered as first-line add-on therapy for cutaneous lupus erythematosus that fails to respond adequately to hydroxychloroquine alone, or as monotherapy in patients who develop hydroxychloroquine-induced retinal toxicity. 1

Current Indications

Cutaneous Lupus Erythematosus

• Quinacrine is specifically recommended for cutaneous manifestations of SLE when hydroxychloroquine monotherapy provides inadequate control 1
• The 2019 EULAR guidelines explicitly state that quinacrine can be considered in patients with cutaneous manifestations and HCQ-induced retinal toxicity 1
• Quinacrine demonstrates particular efficacy in subacute cutaneous lupus erythematosus, with all patients in combination therapy studies showing significant improvement or complete clearance 2
• For chronic cutaneous lupus erythematosus, approximately 55% of refractory cases respond to quinacrine when other antimalarials have failed 3

Giardiasis

• Quinacrine is not mentioned in current malaria treatment guidelines as a first-line agent 1
• Historical use for giardiasis exists, but this is not addressed in contemporary guidelines provided

Recommended Dosing Regimens

Standard Dosing for Cutaneous Lupus

• Initial dose: 100 mg daily as monotherapy or in combination with chloroquine/hydroxychloroquine 4, 3
• Alternative dosing: 100-200 mg/day depending on disease severity and response 3
• Combination therapy protocol: Chloroquine 100 mg three times daily plus quinacrine 65 mg three times daily 2

Maintenance and Tapering

• Once clinical remission is achieved (typically by 4 months), taper to three times weekly dosing 4
• Improvement is typically observed within the first month of treatment 4
• Complete response usually occurs by the fourth month 4

Contraindications

Absolute Contraindications

• Hypersensitivity to quinacrine or related compounds 5
• Psoriasis (risk of severe exacerbation) 5
• Porphyria 5
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency (hemolysis risk) 5

Relative Contraindications

• Severe hepatic impairment 5
• Severe renal impairment 5
• History of psychosis or severe psychiatric disorders 5
• Pregnancy (limited safety data) 5

Major Adverse Effects

Common and Benign

• Yellow skin discoloration (most common, dose-dependent, reversible) 4, 5
• Nausea, vomiting, diarrhea 5
• Mild gastrointestinal upset 5

Serious but Rare

• Cutaneous pigmentation (blue-black discoloration in sun-exposed areas) 5
• Aplastic anemia (extremely rare) 5
• Hepatotoxicity (rare, monitor liver function) 5
• Exfoliative dermatitis (rare) 5
• Psychosis or severe psychiatric reactions (rare) 5
• Lichenoid drug eruptions 5

Critical Advantage Over Hydroxychloroquine

• Quinacrine does NOT cause retinal toxicity, making it the preferred alternative when hydroxychloroquine must be discontinued due to retinopathy 1, 4, 5

Clinical Pearls and Common Pitfalls

When to Use Quinacrine

• First consideration: Add quinacrine to existing hydroxychloroquine therapy for inadequate cutaneous disease control 1, 2
• Second consideration: Switch to quinacrine monotherapy if hydroxychloroquine causes retinal toxicity 1, 4
• Particularly effective for treatment-resistant chronic and subacute cutaneous lupus erythematosus 3, 2

Monitoring Requirements

• Baseline complete blood count and liver function tests 5
• Periodic monitoring of CBC and LFTs during therapy 5
• No ophthalmologic monitoring required (major advantage over hydroxychloroquine) 4, 5
• Counsel patients about expected yellow skin discoloration to prevent unnecessary discontinuation 4

Combination Therapy Strategy

• The chloroquine-quinacrine combination may be superior to antimalarial monotherapy, especially for subacute cutaneous lupus 2
• When combining with hydroxychloroquine, continue hydroxychloroquine at ≤5 mg/kg actual body weight per day 1
• Side effects are generally mild and resolve with dose reduction or cessation 3

Availability Concerns

• Quinacrine is currently unavailable in the United States, creating a significant treatment gap for refractory cutaneous lupus patients 6
• Availability varies by country; confirm local access before prescribing 4
• When unavailable, consider alternative systemic therapies including methotrexate, dapsone, or retinoids for refractory cutaneous disease 1