Thymosin Alpha-1

What it is

Thymosin alpha-1 (thymalfasin, brand name Zadaxin) is a synthetic 28-amino-acid peptide derived from thymic tissue that modulates immune cell activity, including T cells and dendritic cells. It is approved as a prescription drug in more than 30 countries for chronic hepatitis B, chronic hepatitis C in combination with interferon, and as a cancer or vaccine adjunct in some markets, but the manufacturer's own documentation states it has not been approved for sale in the United States or Europe, and it has no FDA drug label. Evidence quality is mixed and skews older. Small trials from the 1990s and 2000s support modest benefit in chronic hepatitis B and C when paired with interferon, and observational or retrospective studies suggest benefit as an adjunct in some cancers. The most rigorous recent evidence, however, is discouraging: a large 2025 randomized, placebo-controlled phase 3 trial in sepsis (over 1,000 patients) found no reduction in 28-day mortality, contradicting an earlier, smaller positive trial from 2013. A retrospective COVID-19 study reported a mortality benefit, but this has not been confirmed in a randomized trial. Reported side effects are mostly mild injection-site reactions, though many supporting trials are small, open-label, older, or manufacturer-summarized, so independent confirmatory data remain limited for most indications.

Dose ranges

Study-backed ranges carry a source you can open. Community ranges are widely reported but not clinically established - treat them as what people do, not as advice.

Reconstitution & storage

The clinical single-dose Zadaxin vial (1.6 mg) is labeled for reconstitution with 1 mL of sterile water for injection immediately before use, yielding a concentration of 1.6 mg/mL, and the labeling states the reconstituted product should be used immediately with no stated shelf life once mixed. Research-sold multi-dose vials (commonly 5 mg or 10 mg) are reconstituted by vendors and community sources with roughly 1 to 3 mL of bacteriostatic water; those volumes and any claimed post-reconstitution refrigerated storage window are community-reported and not clinically validated for this product.

Interactions & cautions

No formal drug-drug interaction studies for thymosin alpha-1 have been published. It has been studied and used clinically in combination with interferon-alpha for hepatitis B, hepatitis C, HIV, and some cancer protocols without evidence of added toxicity in those trials, so combination with interferon is a standard studied approach rather than a flagged interaction. The clinically important caution is pharmacodynamic rather than a drug interaction in the strict sense: because thymosin alpha-1 is an immune-stimulating peptide, ex-US prescribing information and an independent peer-reviewed review both state it is contraindicated in patients who are being deliberately immunosuppressed, such as organ transplant recipients, unless the potential benefit is judged to clearly outweigh the risk.

Questions people ask

Sources

1. [1]DailyMed search results for "thymalfasin"regulatoryConfirms DailyMed returns zero drug label results for thymalfasin (or thymosin alpha), consistent with the product having no FDA-approved US label.
2. [2]Zadaxin Product Monograph (SciClone Pharmaceuticals)regulatoryManufacturer monograph states verbatim that 'ZADAXIN has not been approved for sale in the United States or Europe,' that it 'is approved in over 30 countries,' gives its chemical structure (28 amino acids, molecular weight 3108), and summarizes dosing (0.6 to 9.6 mg/m2 or 1 mg to 16 mg, mostly subcutaneous biweekly) and safety data (more than 3,000 patients in over 70 studies, no serious adverse experiences reported).
3. [3]Zadaxin (Thymalfasin): Side Effects, Uses, Dosage, Interactions, Warnings (RxList)referenceGives reconstitution instructions (1.0 mL sterile water for injection to 1.6 mg/mL), storage (2-8 C, use immediately after reconstitution), the 1.6 mg twice-weekly hepatitis dosing regimen, and the contraindication in deliberately immunosuppressed patients such as organ transplant recipients.
4. [4]Thymalfasin, PubChem Compound Summary (CID 16130571)referenceConfirms chemical identity: compound name Thymalfasin, molecular formula C129H215N33O55, PubChem CID 16130571.
5. [5]Thymosin alpha 1: A comprehensive review of the literature (Dominari et al, World J Virol 2020) PMID 33362999reviewPeer-reviewed review stating thymalfasin is approved in more than 35 countries for hepatitis B and C and holds FDA orphan drug designation for melanoma, chronic active hepatitis B, DiGeorge anomaly, and hepatocellular carcinoma; gives dosing regimens for hepatitis B (1.6 mg SC twice weekly), sepsis (1.6 mg SC twice daily for 5 days), cancer (0.8-16 mg), and COVID-19 (10 mg SC once daily for at least 7 days); and states it is contraindicated in immunosuppressed patients such as organ transplant recipients.
6. [6]Immune Modulation with Thymosin Alpha 1 Treatment (King & Tuthill, Vitamins and Hormones 2016) PMID 27450734reviewPeer-reviewed review describing thymosin alpha-1's mechanism as pleiotropic immune modulation acting through Toll-like receptors on dendritic and myeloid cells, supporting the general mechanism-of-action framing.
7. [7]The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial (Wu et al, Critical Care 2013) PMID 23327199studyRandomized trial (n=361; 180 control, 181 thymosin alpha-1) reporting 28-day mortality of 26.0% versus 35.0% (relative risk 0.74, 95% CI 0.54 to 1.02), the basis for the sepsis dose range and the ETASS versus TESTS comparison discussed in the FAQ.
8. [8]The efficacy and safety of thymosin alpha1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial (Wu et al, BMJ 2025) PMID 39814420studyLarge phase 3 randomized placebo-controlled trial (n=1,089; 542 thymosin alpha-1, 547 placebo) given subcutaneously every 12 hours for 7 days, finding 28-day mortality of 23.4% versus 24.1% (hazard ratio 0.99, 95% CI 0.77-1.27, P=0.93), concluding no clear mortality benefit in sepsis.
9. [9]Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial (Sherman et al, Hepatology 1998) PMID 9537454studyUS randomized double-blind trial (n=109) of thymosin alpha-1 1.6 mg SC twice weekly plus interferon versus interferon alone versus placebo, reporting end-of-treatment biochemical response of 37.1% versus 16.2% (P=0.04), supporting the hepatitis C dose range and overview claim of modest combination benefit.
10. [10]Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial (Andreone et al, J Viral Hepat 2004) PMID 14738560studyRandomized pilot trial (n=41) showing combination therapy achieved significantly higher end-of-treatment virological response than interferon monotherapy (P=0.03), though sustained response rates were comparable at follow-up, supporting the honest caveat that hepatitis C benefit is often not durable.
11. [11]Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells (Liu et al, Clinical Infectious Diseases 2020) PMID 32442287studyRetrospective study of 76 severe COVID-19 cases reporting thymosin alpha-1 treatment significantly reduced mortality (11.11% vs 30.00%, P=.044) and restored CD4/CD8 T-cell counts, the basis for the COVID-19 mention in the overview (with the caveat that this is retrospective, not randomized, evidence).
12. [12]Thymosin alpha 1 as an adjunct to influenza vaccination in the elderly: rationale and trial summaries (Ershler et al, Ann NY Acad Sci 2007) PMID 17600281reviewPeer-reviewed review of trials showing thymosin alpha-1 enhanced antibody responses to influenza vaccination in elderly subjects, supporting the vaccine-adjuvant dose range and context.
13. [13]Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma (Maio et al, J Clin Oncol 2010) PMID 20194853studyRandomized phase 2 trial (n=488) testing thymosin alpha-1 at 1.6, 3.2, and 6.4 mg SC with dacarbazine plus interferon, reporting median overall survival of 9.4 versus 6.6 months (hazard ratio 0.80, 95% CI 0.63-1.02, P=.08), a non-statistically-significant trend used to support the cancer dose range while noting the result did not reach significance.
14. [14]Thymalfasin, a promising adjuvant therapy in small hepatocellular carcinoma after liver resection (He et al, Medicine (Baltimore) 2017) PMID 28422855studyRetrospective cohort (n=206) using thymalfasin 1.6 mg SC twice weekly for at least 26 weeks after liver resection, reporting improved 1/3/5-year overall survival (97.7%/90.6%/82.9% vs 95.1%/80.5%/62.9%, P=.014) versus resection alone, supporting the cancer-adjuvant dosing and overview claim of retrospective benefit in hepatocellular carcinoma.
15. [15]Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: a systematic review and meta-analysis (Tian et al., 2025) PMID 40599771reviewMeta-analysis of 5 randomized controlled trials (706 patients with severe acute pancreatitis) finding thymosin alpha-1 reduced extrapancreatic infection rates (RR=0.56, P=0.0005) and improved CD4+ and CD4+/CD8+ immune parameters, used to support the general statement that evidence outside hepatitis and sepsis is limited to small/pooled trials in adjacent critical-care conditions.
16. [16]Efficacy of thymosin alpha-1 plus peginterferon alpha-2a combination therapy compared with peginterferon alpha-2a monotherapy in HBeAg-positive chronic hepatitis B: a prospective, multicenter, randomized, open-label study (Scandinavian Journal of Gastroenterology 2012) PMID 22726105studyRandomized trial (26 combination vs 25 peginterferon-alone patients) finding no statistically significant difference in combined response rate at end of treatment (15.4% vs 12.0%, P=0.725), used as an honest counterexample showing not all hepatitis B trials favor thymosin alpha-1.
17. [17]Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study (Expert Opinion on Biological Therapy 2018) PMID 30063860studyRandomized trial (351 combination vs 339 entecavir-monotherapy patients with HBV-related compensated cirrhosis) finding no significant difference in the composite endpoint of liver decompensation, hepatocellular carcinoma, or death, another honest counterexample of a large, largely negative hepatitis B trial.
18. [18]Thymosin alpha-1 (Ancell, Phipps & Young, American Journal of Health-System Pharmacy 2001) PMID 11381492reviewPharmacy literature review reporting a half-life of approximately 2 hours, time to peak concentration within 2 hours, return to baseline by 24 hours, and a standard dose of 1.6 mg SC twice weekly, the basis for the half-life value.
19. [19]Pharmacokinetics of thymosin alpha1 after subcutaneous injection of three different formulations in healthy volunteers (Rost et al, International Journal of Clinical Pharmacology and Therapeutics 1999) PMID 10027483studyDedicated pharmacokinetic study in healthy volunteers at a 900 microg/m2 (about 1.6 mg) subcutaneous dose, reporting elimination half-life under 3 hours, time to maximum concentration of 1-2 hours, and no evidence of drug accumulation, the primary source for the half-life value.