Thymosin α-1
Thymosin alpha-1 (thymalfasin, brand name Zadaxin) is a 28-amino-acid thymic peptide that modulates the immune system. On the Zadaxin label, the dose is 1.6 mg injected under the skin twice a week: for 6–12 months in chronic hepatitis B, or 12 months alongside interferon in hepatitis C. Sepsis trials used 1.6 mg once or twice a day for about a week, with mixed results. It is approved in more than 35 countries but not by the US FDA, so there is no FDA-approved dose.
Thymosin alpha-1 dosage: the label and published trials
The labeled dose is 1.6 mg subcutaneously twice a week. This is the Zadaxin dose for chronic hepatitis B, where it is given for 6–12 months alone or with interferon, and for chronic hepatitis C, where it is given for 12 months with interferon only. Patients under 40 kg get 40 mcg/kg. The powder is mixed with 1.0 mL of the supplied diluent just before injection, and the label says it must not be given intravenously.7 That wording comes from Singapore’s registered product information. There is no US label, because the FDA has not approved thymosin alpha-1 for any use.
Trials outside hepatitis mostly used the same 1.6 mg unit but gave it much more often, and for days instead of months:
| Setting | Dose | Schedule | What it found |
|---|---|---|---|
| Chronic hepatitis B, Taiwan RCT (98 patients)8 | 1.6 mg SubQ | Twice weekly for 26 or 52 weeks | Complete virological response at 18 months: 40.6% (26 wk) and 26.5% (52 wk) vs 9.4% untreated |
| Chronic hepatitis B, US phase III (97 patients)5 | 1.6 mg SubQ | Twice weekly for 6 months | Complete response 14% vs 4% placebo; not significant (P = 0.084) |
| Severe sepsis, ETASS (361 patients)2 | 1.6 mg SubQ | Twice daily for 5 days, then once daily for 2 days | 28-day mortality 26.0% vs 35.0%; P = 0.062 in the unstratified analysis |
| Sepsis, TESTS phase 3 (1,106 patients)1 | 1.6 mg SubQ | Every 12 hours for up to 7 days | 28-day mortality 23.4% vs 24.1% placebo; no clear benefit |
| Sepsis RCTs, systematic review3 | 1.6 mg SubQ | Once daily (14 trials) or twice daily (5 trials) | Pooled mortality reduction in older, smaller trials |
| Hospitalized COVID-19, meta-analysis4 | 1.6 mg to 10–30 mg | Every other day to twice daily | No significant effect on mortality |
A 2020 literature review describes single doses from 0.8 to 6.4 mg, and multi-day courses from 1.6 to 16 mg over five to seven days. It reports that the drug was well tolerated across these ranges, with side effects mostly limited to injection-site reactions.9 Every figure on this page comes from a supervised hepatitis, sepsis or COVID-19 setting. None of it is a dose for healthy people or for self-directed use.
Thymosin α-1 reconstitution calculator
Thymosin α-1 dilution chart & full calculator →Typical dosing
| Goal | Range | Route | Frequency |
|---|---|---|---|
| Chronic hepatitis B (Zadaxin label — approved in ~35 countries, not the US) | 1.6 mg (900 mcg/m2); 40 mcg/kg if under 40 kg | SubQ (never IV) | 2x weekly for 6-12 months, as monotherapy or with interferon |
| Chronic hepatitis C (Zadaxin label) | 1.6 mg (900 mcg/m2); 40 mcg/kg if under 40 kg | SubQ | 2x weekly for 12 months, in combination with interferon only |
| Severe sepsis (ETASS trial regimen) | 1.6 mg | SubQ | 2x daily for 5 consecutive days, then 1x daily for 2 days |
| Sepsis (TESTS phase 3, 2025 — no 28-day mortality benefit) | 1.6 mg | SubQ | Every 12 hours for up to 7 days |
| Reconstitution and US status | Reconstitute with 1.0 mL of the supplied diluent immediately before use | SubQ | No FDA-approved dose exists — all of the above are non-US labels or trial protocols |
Ranges compiled from research literature — not a prescription.
How it works
Thymosin alpha-1 is a synthetic version of a peptide originally isolated from thymic tissue (thymosin fraction 5). It does not act as a direct antimicrobial or antiviral agent; instead it functions as an immune modulator. Research shows it binds Toll-like receptors (TLR2, TLR9, and others) on dendritic cells and macrophages, triggering NF-κB and MAPK signaling that drives dendritic cell maturation — upregulating MHC class I/II and costimulatory molecules (CD80, CD86) — and shifting T-cell differentiation toward Th1/cytotoxic phenotypes while also supporting regulatory T-cell balance.
Clinically, this mechanism underlies its longest-standing use: as Zadaxin, an adjuvant therapy for chronic hepatitis B and C, approved in more than 35 countries but never by the US FDA. The randomized trials in chronic hepatitis B do not agree with each other. A trial in Taiwan found more complete virological responses 18 months after a 26-week course than in untreated controls (40.6% vs 9.4%). A US phase III placebo-controlled trial found 14% vs 4%, which was not statistically significant, and its authors wrote that the results did not confirm earlier reports.
More recent research has tested thymosin alpha-1 as an adjunct in sepsis and COVID-19, conditions marked by immune dysregulation. Earlier trials and meta-analyses (including the ETASS trial) suggested a mortality benefit in sepsis, but the largest and most rigorous trial to date — TESTS, a multicentre phase 3 RCT of 1,106 adults published in 2025 — found no clear reduction in 28-day mortality, a reminder that early promising signals in smaller trials do not always hold up. COVID-19 studies showed a similar pattern: several cohort studies and smaller RCTs reported improved lymphocyte recovery or reduced mortality in moderate-to-severe patients, but a 2023 meta-analysis found no significant effect on mortality, with large differences between studies.
Taken together, thymosin alpha-1 has more extensive human clinical trial data than most investigational peptides, largely because of its decades of international use as Zadaxin. But that same body of evidence is mixed and context-dependent — strong in some hepatitis B/C and sepsis subgroups, inconclusive in others — and it remains unapproved by the FDA for any indication in the United States.
Side effects & safety
- Generally well tolerated in clinical trials; the most common adverse effects reported are mild injection-site reactions such as redness or swelling.
- As an immune-modulating agent, it may theoretically interact with autoimmune conditions or immunosuppressive/immunostimulant medications — clinical supervision is advised.
- Not FDA-approved in the US for any indication; approved as Zadaxin (prescription) in more than 35 countries for specific, medically supervised uses.
- Most long-term human safety data comes from patients with hepatitis B/C, sepsis, or cancer under clinical monitoring, not from healthy populations using it outside medical care.
- Sourcing and purity vary widely outside regulated pharmaceutical supply chains; unregulated or research-labeled material carries contamination and dosing-accuracy risks.
- Anyone considering use should consult a licensed clinician first, especially if pregnant, breastfeeding, immunocompromised, or taking other immune-active therapies.
Research
Primary sources — PubMed.
- Wu J, Pei F, Zhou L, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025;388:e082583. https://pubmed.ncbi.nlm.nih.gov/39814420/
- Wu J, Zhou L, Liu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013;17(1):R8. https://pmc.ncbi.nlm.nih.gov/articles/PMC4056079/
- Liu F, Wang HM, Wang T, et al. The efficacy of thymosin α1 as immunomodulatory treatment for sepsis: a systematic review of randomized controlled trials. BMC Infect Dis. 2016;16:488. https://pmc.ncbi.nlm.nih.gov/articles/PMC5025565/
- Shang W, Zhang B, Ren Y, et al. Thymosin alpha1 use in adult COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Int Immunopharmacol. 2023;114:109584. https://pmc.ncbi.nlm.nih.gov/articles/PMC9754924/
- Mutchnick MG, Lindsay KL, Schiff ER, et al. Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study. J Viral Hepat. 1999;6(5):397-403. https://pubmed.ncbi.nlm.nih.gov/10607256/
- Romani L, Bistoni F, Perruccio K, et al. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood. 2006;108(7):2265-2274. https://pubmed.ncbi.nlm.nih.gov/16741252/
- Health Sciences Authority, Singapore — National Drug Formulary. ZADAXIN INJECTION (SIN07483P): product information. https://www.ndf.gov.sg/about-drugs/product-information/sin07483p/
- Chien RN, Liaw YF, Chen TC, Yeh CT, Sheen IS. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology. 1998;27(5):1383-1387. https://pubmed.ncbi.nlm.nih.gov/9581695/
- Dominari A, Hathaway D III, Pandav K, et al. Thymosin alpha 1: a comprehensive review of the literature. World J Virol. 2020;9(5):67-78. https://pmc.ncbi.nlm.nih.gov/articles/PMC7747025/