Interferon alfa formulations

Therapeutic formulations contain a recombinant form of IFN-a (either interferon alfa-2a or interferon alfa-2b). These are available as powders for reconstitution or as prefilled injection pens. The drug is administered by subcutaneous injection (or intravenous for reconstituted powder formulations) and intramuscular injection. The dosage is usually stated as units per millilitre (refer to BNF for various preparations and dosages). Powder formulations of interferon alfa-2b also contain glycine, sodium phosphate (mono- and dibasic) and human albumin prefilled pens contain sodium chloride, edetate disodium, polysorbate 80 and m-cresol as a preservative. 

Interferon alfa-2a formulations contain excipients sodium chloride, polysorbate, ammonium acetate, and benzyl alcohol as a preservative. Interferon alfa is also approved for use in the treatment of several other disorders. 

Peginterferon formulations are also available (polyethyleneglycol-conjugated interferon alfa). These have an extended serum half-life compared with non-conjugated forms. 

The reported side-effects of interferon alfa include cardiovascular problems such as arrhythmia, tachycardia and hypotension in the absence of history of such conditions, severe myelosuppression, depression and suicidal behaviour, opthalmic disorders, anorexia and flu-like symptoms and hypersensitivity reactions. Mr JJ should be advised of these and of the actions to be taken. The patient should be informed that under no circumstances should he switch treatments as different formulations may contain different dosages. Furthermore, he should be made aware of the proper disposal of used pens/syringes and to take extra care if blood enters the dispensers, as described in the product literature. Hepatitis B support groups are available. Dietary advice may be offered as cytokine-based treatments often cause reduced appetite. 

Imiquimod is an immune response enhancer that induces production of interferon and several other cytokines. It is used, in formulations containing 5%, to treat external genital and perianal warts/condylomata acuminata in adults (1). As imiquimod-treated warts regress, serum concentrations of interferon-alfa, interferon-beta, interferon-gamma, and tumor necrosis factor rise (2). Trials of imiquimod have failed to identify any particular systemic or laboratory abnormalities. 

In 1530 patients with chronic hepatitis C, pegylated interferon alfa-2b had a similar profile of adverse effects to unmodified interferon alfa-2b, but with more frequent dose-hmiting neutropenia (10). No particular adverse effect has emerged since the use of this new formulation. 

Although the adverse effects profiles of the currently available formulations of interferon alfa are very similar, patients who have adverse effects with one formulation can be successfully re-treated with another type of interferon alfa. This has been shown in 22 patients in whom lymphoblastoid interferon alfa was withdrawn because of severe adverse effects (leukopenia, thrombocytopenia, thyroid disorders, and psychiatric disturbances) and were successfully re-treated with similar dosages of leukocyte interferon alfa (22). Only one of these patients had severe leukopenia again. 

The respiratory adverse effects of interferon alfa include interstitial pneumonitis (38), which is rare. Since the first description of interstitial pneumonitis associated with interferon alfa in Japanese patients who also used the popular Sho-saiko-t herbal formulation, similar cases have been described in Western patients, suggesting that interferon alfa can be the sole cause in some patients (SED-13,1091) (SEDA-20, 326) (SEDA-21, 370) (39,40). 

Nakamura H (2005). Pegylated interferon alfa-2b formulation. Farmada. 41 769-761. 

Zhi, J., Teller, S.B. et al., 1995, Influence of human serum albumin content in formulations on the bioequivalency of interferon alfa-2b given by subcutaneous injection in healthy male volunteers. J Clin Pharmacol 35 281-4. 

---