Zadaxin

Zadaxin

thymalfasin

Manufacturer:

SciClone

Distributor:

DKSH
Full Prescribing Info
Contents
Thymosin α1 (thymalfasin).
Description
Each vial also contains the following excipients: Mannitol 50 mg and sodium phosphate buffer to adjust the pH to 6.8. The diluent used is sterile water for injection.
Zadaxin for SC injection is a purified, sterile, lyophilized preparation of chemically synthesized thymosin α1.
Thymosin α1 is an acetylated polypeptide with the following sequence: Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH. It has a molecular weight of 3108 daltons and a pl of 3.8.
Thymosin α1 is also known as thymalfasin.
Action
Pharmacology: The mechanism of action of Zadaxin in treating chronic hepatitis B is not completely understood. In various in vitro assays, the peptide shows promotion of T cell maturation by mitogen-stimulated peripheral blood lymphocytes; increase in production of various lymphokines, eg interferon α, interferon γ, interleukin 2 (IL-2) and interleukin 3 (IL-3) by T cells following antigen or mitogen activation; and increase in the levels of lymphokine receptors on T cells. It also enhances both allogeneic and autologous human mixed lymphocyte reactions by activation of T4 (helper/inducer) cells. Thymosin α1 may influence recruitment of prenatural killer (NK) cells, which then become cytotoxic after exposure to interferon. In vivo, thymosin α1 enhances IL-2 receptors and production of IL-2 in concanavalin A-stimulated mouse lymphocytes.
Pharmacokinetics: At 900 mcg/m2, thymosin α1 given SC results in peak plasma concentrations of 25-30 ng/mL approximately 1 hr after injection. Peak levels are maintained for 6 hrs and return to baseline over the following 18 hrs. Repeated injections twice a week for 15 weeks result in a very slight increase in baseline plasma thymosin α1 concentration.
Indications/Uses
Chronic Hepatitis B: Treatment of chronic hepatitis B when used as monotherapy or combination therapy with interferon in patients ≥18 years with compensated liver disease and hepatitis B virus (HBV) replication (serum HBV DNA positive).
Studies in patients who have been serum hepatitis B surface antigen (HBsAg) positive for at least 6 months with elevated serum alanine aminotransferase (ALT) demonstrate that treatment with Zadaxin therapy can produce virological remission (loss of serum HBV DNA) and normalization of serum aminotransferases. Zadaxin therapy resulted in the loss of serum HBsAg in some responding patients.
Vaccine Adjuvant: As an adjuvant for influenza vaccination in immunocompromised patients. Zadaxin was studied in various dosing regimens as an adjuvant for influenza vaccine in elderly patients as an adjuvant for both influenza and hepatitis B vaccines in chronic hemodialysis patients who failed to achieve adequate antibody titers from various immunization.
Dosage/Direction for Use
Treatment of Chronic Hepatitis B: The recommended dose when used as a monotherapy or in combination with interferon (at the labeled dose and schedule for interferon) is 1.6 mg (900 mcg/m2) administered SC twice a week with doses separated by 3 or 4 days. Therapy should be continued for 6 months (52 doses) without interruption. Patients weighing <40 kg should receive a Zadaxin dose of 40 mcg/kg.
Vaccine Adjuvant: The recommended dose when used as an enhancement to viral vaccines is 900 mcg/m2 (1.6 mg) administered SC twice a week with doses separated by 3 or 4 days and the 1st dose given coincident with the vaccine. Therapy should be continued for 4 weeks (a total of 8 doses) after a single-dose vaccine immunization regimen. For a multi-dose vaccine immunization regimen, therapy should continue twice a week between vaccinations and for 3 weeks (a total of 5-6 doses) after the last vaccination.
Zadaxin should not be given IM or IV. It should be reconstituted with 1 mL of the diluent provided immediately prior to use. It should be used immediately after reconstitution. At the discretion of the physician, the patient may be taught to self-administer the medication.
Overdosage
There are no reported instances of deliberate or accidental overdosage in humans. Animal toxicology studies have shown no adverse reactions in doses of 20 mg/kg, the highest level studied.
Contraindications
Patients with a history of hypersensitivity to thymosin α1 or any component of the injection. Because Zadaxin therapy appears to work by enhancing the immune system, it should be considered contraindicated in patients who are being deliberately immunosuppressed, for instance transplant patients, unless the potential benefits of the therapy clearly outweigh the potential risks.
Special Precautions
Information for Patients: Patients receiving Zadaxin treatment should be directed in its appropriate use and informed of the benefits and risks associated with treatment. If home use is prescribed, a puncture-resistant container for the disposal of used syringes and needles should be supplied to the patient. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of syringes or needles.
Laboratory Tests: Liver function tests, including serum ALT, albumin and bilirubin, should be evaluated periodically during treatment. HBeAg (hepatitis B envelope antigen), HBsAg, HBV DNA and ALT should be evaluated at the end of treatment, as well as 2, 4 and 6 months after treatment, since patients may become virologic responders during the 6 months following treatment.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Long-term studies with Zadaxin have not been done to determine carcinogenicity. Mutagenicity studies with Zadaxin showed no adverse findings.
Use in Pregnancy: Pregnancy Category C: Animal reproduction studies have shown no differences in fetal abnormalities in control animals and animals given Zadaxin. It is not known whether Zadaxin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Zadaxin should be given to a pregnant woman only if clearly needed.
Use in Lactation: It is not known whether Zadaxin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Zadaxin is administered to a nursing woman.
Use in Children: Safety and effectiveness have not been established in patients <18 years.
Use In Pregnancy & Lactation
Use in Pregnancy: Pregnancy Category C: Animal reproduction studies have shown no differences in fetal abnormalities in control animals and animals given Zadaxin. It is not known whether Zadaxin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Zadaxin should be given to a pregnant woman only if clearly needed.
Use in Lactation: It is not known whether Zadaxin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Zadaxin is administered to a nursing woman.
Adverse Reactions
Zadaxin is generally well tolerated. During clinical studies involving >2000 individuals distributed over all age groups, no clinically significant adverse reactions attributable to thymosin α1 administration were reported (see table).

Click on icon to see table/diagram/image

Immune Disorders: Autoimmune liver disease and primary immune deficiency.
Adverse experiences have been infrequent and mild, consisting primarily of local discomfort at the injection site and rare instances of erythema. Transient muscle atrophy, polyarthralgia with hand edema and rash at the injection site. As with any new drug, it is possible that expanded commercial use of the drug could reveal rare adverse reactions not observed in clinical studies. A transient increase in ALT to more than twice baseline value (flare) can occur during Zadaxin therapy for chronic hepatitis B. When ALT flare occurs, Zadaxin should generally be continued unless signs and symptoms of liver failure are observed.
Drug Interactions
Interactions between Zadaxin and other drugs have not been fully evaluated. Caution should be exercised when administering Zadaxin therapy in combination with other immune-modulating drugs. Zadaxin should not be mixed with any other drug.
Storage
Store between 2°C and 8°C (36°F and 46°F).
ATC Classification
L03AX - Other immunostimulants ; Used as immunostimulants.
Presentation/Packing
Powd for inj (vial) 1.6 mg (single use) x 1 mL + amp (diluent) 1 mL x 2's.
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