Quinacrine
Antimalarial agent used in dermatology for lupus, dermatomyositis, and refractory skin conditions.
Quinacrine (also known as mepacrine or atabrine) is a synthetic acridine derivative originally developed as an antimalarial agent during World War II. In modern dermatology, it serves as an adjuvant therapy primarily for cutaneous lupus erythematosus (CLE) refractory to standard antimalarials like hydroxychloroquine (HCQ) or chloroquine (CQ). Its unique mechanism includes immune modulation, anti-inflammatory effects, and photoprotection due to UV-absorbing yellow pigmentation.
Unlike HCQ and CQ, quinacrine does not accumulate in the retina, minimizing retinopathy risk, and requires no routine ophthalmologic monitoring. It is compounded as 100 mg tablets since no commercial formulation exists in the U.S. Typical dosing is 100 mg daily, often combined with HCQ 200–400 mg/day for synergistic effects in refractory cases.
What is quinacrine?
Quinacrine hydrochloride is a fluorescent yellow compound from the acridine family, structurally distinct from quinoline-based antimalarials (HCQ/CQ). Historically, it treated malaria when quinine supplies dwindled, later repurposed for rheumatic diseases and dermatoses. Its dermatologic applications stem from inhibiting proinflammatory cytokines like TNF-α and IFN-α from monocytes and dendritic cells, plus toll-like receptor modulation.
- Chemical properties: Lipophilic, accumulates in lysosomes, binds DNA/RNA to disrupt immune signaling.
- Pharmacokinetics: Oral bioavailability ~80%, half-life ~5–14 days, hepatic metabolism, fecal excretion.
- Unique feature: Yellow pigmentation causes reversible skin/mucosal discoloration in 20–30% of users.
Who gets quinacrine?
Quinacrine targets patients with refractory CLE subtypes unresponsive to HCQ/CQ monotherapy, including:
- Discoid lupus erythematosus (DLE): Scarring plaques on face/scalp.
- Subacute cutaneous lupus erythematosus (SCLE): Annular/psoriasiform photosensitive lesions.
- Acute cutaneous lupus erythematosus (ACLE): Malar rash in systemic lupus.
- Dermatomyositis: Heliotrope rash, Gottron papules refractory to standard therapy.
- High-risk patients: HCQ intolerance, retinopathy concerns, severe photosensitivity.
Dermatologists and rheumatologists in academic/specialty clinics prescribe it most frequently.
What does quinacrine treat?
Cutaneous lupus erythematosus
Primary indication: Adjuvant for HCQ/CQ-refractory CLE, improving skin scores by 50–80% in observational studies. Combination therapy reduces flares, scarring, and photosensitivity.
| CLE Subtype | Key Features | Quinacrine Response |
|---|---|---|
| Discoid (DLE) | Thick, scaly, atrophic scars | Lesion clearance in 60–70% refractory cases |
| Subacute (SCLE) | Annular, sun-induced | Reduced flares via photoprotection |
| Acute (ACLE) | Malar erythema | Synergy with HCQ |
Dermatomyositis
In cutaneous dermatomyositis, quinacrine (100 mg/day) added to HCQ/CQ resolves refractory rashes like heliotrope erythema and papules. Case series report marked improvement without added toxicity.
Other indications
- Refractory solar urticaria, polymorphous light eruption.
- Adjunct in systemic lupus erythematosus (SLE) skin involvement.
- Historic uses: Giardiasis, tapeworms (discontinued).
How effective is quinacrine?
Response rates: 60–85% in refractory CLE when combined with HCQ. A Lupus Science & Medicine review highlights its value in HCQ failures. Observational data show sustained remission in DLE/SCLE.
- Cavazzana et al. (2009): HCQ + quinacrine improved skin in 75% lupus patients.
- Actas Dermo cases: Complete rash resolution in dermatomyositis after 6–7 months.
- Meta-analyses confirm low relapse post-discontinuation.
Case studies
Case 1: Refractory discoid lupus
32-year-old female with facial/scalp plaques persistent on HCQ. Added quinacrine 100 mg/day: 80% clearance at 3 months, no scarring progression.
Case 2: SCLE in photosensitive patient
20-year-old with summer flares despite sunscreen. HCQ + quinacrine: Lesions resolved, flares reduced.
Case 3: Dermatomyositis
Patient with heliotrope rash post-prednisone/methotrexate failure. HCQ 400 mg + quinacrine 100 mg + low-dose prednisone: Significant improvement at 6 months, only yellowing side effect.
Case 4: Chronic CLE
Positive ANA, lymphocytopenia; failed multiple agents. Colchicine + HCQ + quinacrine: Marked lesion reduction.
Quinacrine dosing regimen
Adults: 100 mg orally once daily (maintenance). Load with 100 mg BID x 1 week if rapid control needed.
- Combination: HCQ 200–400 mg + quinacrine 100 mg daily.
- Children: 2 mg/kg/day (max 100 mg).
- Duration: 6–24 months; taper if remission.
- Compounding: 100 mg capsules/tablets from specialty pharmacies.
Side effects of quinacrine
Well-tolerated; no retinal toxicity. Common: Yellow skin/nails/sclera (reversible, dose-related).
| Side Effect | Frequency | Management |
|---|---|---|
| Skin/mucosal yellowing | 20–30% | Dose reduce to 50 mg; resolves off therapy |
| Gastrointestinal upset | 10–15% | Take with food |
| Psychosis (rare) | <1% | Discontinue; contraindicated in schizophrenia |
| Hepatotoxicity | Rare | LFT monitoring q3 months |
Quinacrine monitoring
- Baseline: CBC, LFTs, psych history.
- Ongoing: LFTs q3 months; no eye exams needed.
- Yellowing: Reassure patient; cosmetic only.
Drug interactions
- Avoid primaquine (hemolysis risk).
- CYP2D6 inhibitors may increase levels (e.g., cimetidine).
- Safe with HCQ/CQ, methotrexate, prednisone.
Contraindications and cautions
- Psychiatric disorders (psychosis risk).
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Pregnancy (Category C; limited data).
- Lactation: Avoid.
Frequently asked questions (FAQs)
Q: Is quinacrine FDA-approved for lupus?
A: No, used off-label; compounded in U.S. Supported by expert consensus for refractory CLE.
Q: Does quinacrine cause permanent yellow skin?
A: No, discoloration is reversible within weeks of discontinuation or dose reduction.
Q: How long until quinacrine works for skin lupus?
A: 4–12 weeks for noticeable improvement; full effect at 3–6 months.
Q: Can quinacrine replace hydroxychloroquine?
A: Rarely; best as add-on for synergy, not monotherapy.
Q: Is monitoring required like with HCQ?
A: Minimal; LFTs only, no retinal screening.
References
- Quinacrine for Lupus Skin Symptoms — HDRx Pharmacy. 2023. https://www.hdrx.com/quinacrine-lupus-skin-symptoms-michigan-pharmacy/
- Quinacrine for Lupus — CareFirst Specialty Pharmacy. 2023. https://www.cfspharmacy.pharmacy/blog/post/quinacrine-for-lupus
- Quinacrine Hydrochloride in Lupus Erythematosus — JAMA Dermatology. 1950-10-01. https://jamanetwork.com/journals/jamadermatology/fullarticle/523808
- Quinacrine: A Treatment Option That Should Not Be Overlooked — Actas Dermo-Sifiliográficas. 2017. https://www.actasdermo.org/en-quinacrine-a-treatment-option-that-articulo-S1578219016302360
- Response of Dermatomyositis to Quinacrine — NIH PMC. 2021-02-11. https://pmc.ncbi.nlm.nih.gov/articles/PMC7854791/
- Candidate Drug Replacements for Quinacrine in CLE — NIH PMC. 2020. https://pmc.ncbi.nlm.nih.gov/articles/PMC7577055/
- The Storied Past of Quinacrine HCI — PCCA Blog. 2023. https://www.pccarx.com/Blog/the-storied-past-of-quinacrine-hci
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