Two medicines, side by side
Hydroxychloroquine vs leflunomide
Hydroxychloroquine and leflunomide are both labeled for rheumatoid arthritis. Drugs@FDA records approvals of hydroxychloroquine since 1955 and of leflunomide since 1998. Pharmacies paid $0.149 per hydroxychloroquine 200 mg tablet and $0.324 per leflunomide 10 mg tablet (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. How each works, in its label's words: Hydroxychloroquine, “Malaria Hydroxychloroquine is a 4-aminoquinoline antimalarial [see Microbiology (12.4)] and antirheumatic agent.”; Leflunomide, “Leflunomide is an isoxazole immunomodulatory agent that inhibits dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine synthesis) and has antiproliferative activity.”
Check it at the source: the hydroxychloroquine FDA label on DailyMed (effective October 8, 2024); the leflunomide FDA label on DailyMed (effective June 4, 2025).
Highlights of the hydroxychloroquine record
Hydroxychloroquine (Plaquenil) · label of October 8, 2024
Used for
From the label: indicationsSOVUNA is an antimalarial and antirheumatic indicated for the: Treatment of uncomplicated malaria due to Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax in adult and pediatric patients. (1.1) Prophylaxis of malaria in geographic areas where chloroquine resistance is not reported in adult and pediatric patients. (1.1) Treatment of rheumatoid arthritis in adults. […]
On the market
- Earliest approval on file
- April 18, 1955
- Generic labelers
- 28 labelers
- Pharmacy cost
- $0.149 per tablet
Supply and safety
- Shortage
- A presentation being discontinued
- Recalls
- 2
Highlights of the leflunomide record
Leflunomide (Arava) · label of June 4, 2025
EMBRYO-FETAL TOXICITY and HEPATOTOXICITY WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity Teratogenicity and embryo-lethality occurred in animals administered leflunomide. ( 5.1 , 8.1 ) Exclude pregnancy prior to initiating ARAVA therapy. ( 5.1 , 8.3 ) Advise use of effective contraception in females of reproductive potential during treatment and during a drug elimination procedure.
Used for
From the label: indicationsARAVA is indicated for the treatment of adults with active rheumatoid arthritis (RA). ARAVA is a pyrimidine synthesis inhibitor indicated for the treatment of adults with active rheumatoid arthritis.
On the market
- Earliest approval on file
- September 10, 1998
- Generic labelers
- 16 labelers
- Pharmacy cost
- $0.324 per tablet
Supply and safety
- Shortage
- A presentation being discontinued
- Recalls
- 2
Source: FDA drug labels via openFDA (Hydroxychloroquine label of October 8, 2024, Leflunomide label of June 4, 2025); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do hydroxychloroquine and leflunomide differ on the record?
How each works, in its label's words: Hydroxychloroquine, “Malaria Hydroxychloroquine is a 4-aminoquinoline antimalarial [see Microbiology (12.4)] and antirheumatic agent.”; Leflunomide, “Leflunomide is an isoxazole immunomodulatory agent that inhibits dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine synthesis) and has antiproliferative activity.”
Only the leflunomide label carries a boxed warning.
Both are in FDA's class antirheumatic agents.
Half-life, in each label's words: Hydroxychloroquine, “Results following a single oral dose of a 200 mg tablet demonstrated a half-life of hydroxychloroquine about 40 days in …”; Leflunomide, “Due to the very long half-life of teriflunomide (18–19 days), a loading dose of 100 mg for 3 days was used in clinical …”
Generics: hydroxychloroquine since 1994; leflunomide since 2005 (Drugs@FDA).
| Hydroxychloroquine | Leflunomide | |
|---|---|---|
| Labeled for | Rheumatoid arthritis | Rheumatoid arthritis |
| Pharmacologic class | Antimalarial, Antirheumatic Agent | Antirheumatic Agent |
| How it works (label) | Malaria Hydroxychloroquine is a 4-aminoquinoline antimalarial [see Microbiology (12.4)] and antirheumatic agent. | Leflunomide is an isoxazole immunomodulatory agent that inhibits dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine synthesis) and has antiproliferative activity. |
| Half-life (label) | Results following a single oral dose of a 200 mg tablet demonstrated a half-life of hydroxychloroquine about 40 days in whole blood. | Due to the very long half-life of teriflunomide (18–19 days), a loading dose of 100 mg for 3 days was used in clinical studies to facilitate the rapid attainment of steady-state teriflunomide concentrations. |
| Earliest approval on file (Drugs@FDA) | April 18, 1955 | September 10, 1998 |
| First generic approved | September 30, 1994 | September 13, 2005 |
| Generic labelers (NDC) | 28 labelers | 16 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.149 per tablet (Hydroxychloroquine 200 mg tablet) | $0.324 per tablet (Leflunomide 10 mg tablet) |
| 12-month price change | -8% | -7% |
| Boxed warning | No | Yes |
| Shortage now | A presentation being discontinued | A presentation being discontinued |
| Recalls recorded | 2 | 2 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 151,392 | 104,036 |
| DEA schedule | none | none |
Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)
What next?
- Alternatives to hydroxychloroquine
- every medicine labeled for the same conditions