Interferon alfa dosage

Recommended dosage and monitoring requirements The recommended dose of Roferon-A for chronic hepatitis C is 3 million international units (MIU) three times a week for 12 months. The recommended dose for CML is 9 MIU daily optimal duration of therapy has not been determined. The recommended dose for hairy cell leukemia is 3 MIU daily for 16 to 24 weeks. The recommended dose for AIDS-related Kaposi s sarcoma is 36 MIU daily for 10 to 12 weeks. There are five types of interferon alfa currently available in the United States interferon alfa-2a, peginterferon alfa-2a, interferon alfa-2b, interferon alfacon-1, and interferon alfa n3. Doses are not consistent for these preparations. 

The use of pegylated interferon alfa-2a and pegylated interferon alfa-2b, as a result of slower clearance resulting in substantially longer terminal half-lives and steadier drug concentrations, allows for less frequent dosing in patients with chronic HCV infection. Renal elimination accounts for about 30% of clearance, and clearance is approximately halved in subjects with impaired renal function dosage must therefore be adjusted. 

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. 

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. 

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. 

In one study in 119 patients treated with interferon alfa and ribavirin for chronic hepatitis C, in whom neutropenia was not considered as a cause for exclusion or dosage modification, the neutrophil count fell by an average of 34% (31-74%) (226). During the course of treatment, 32 patients had at least one neutrophil count below 1 X 10 /1, 11 had a neutrophil count below 0.75 x 10 /1, and 2 had a neutrophil count below 0.5 x 10 /1 however, none of these patients required dosage modification because of neutropenia. None of the 22 patients who developed documented or suspected bacterial infections... 

A review of 15 other available reports of renal insufficiency and proteinuria in patients with chronic myeloid leukemia or other malignancies confirmed that the histological spectrum of renal lesions associated with interferon alfa is varied, and includes membranous glomerulonephritis, minimal change glomerulonephritis, acute interstitial nephritis, hemolytic-uremic sjmdrome, and thrombotic microangiopathy. Renal comphcations were reversible in nine patients three patients had persistent proteinuria, and four had persistent renal dysfunction, of whom three required chronic hemodialysis. Two-thirds of the patients developed renal comphcations within 1 month of treatment with interferon alfa, and one-third had received a relatively low dosage of interferon alfa (9-15 MU/week). 

Meyerson s phenomenon, multiple focal and transient eczematous eruptions around melanocjdic nevi, has been reported in a 24-year-old man when the dosage of interferon alfa for Behqet s disease was doubled (303). 

Reduced efficacy of human erythropoietin, requiring increased erythropoietin dosages, has been clearly documented in several patients receiving interferon alfa... 

A 55-year-old man with chronic hepatitis C presented with a pruritic papular eruption on the trunk lasting 2 weeks. He had multiple, erythematous, excoriated papules on the neck, trunk, upper arms, and thighs. The lesions appeared 2 weeks after combination therapy with oral ribavirin and subcutaneous interferon alfa-2b. He had previously been treated with interferon alfa alone (in the same dosage). On withdrawal of ribavirin the lesions gradually faded, but they returned 1 week after reintroduction. 

A woman stabilised on long-term warfarin 2.5 to 3.5 mg daily had a prothrombin time rise from 16.7 to 20.4 seeonds after receiving 6 million units of interferon-alfa daily for 10 days, then three times a week. Her serum warfarin levels rose from about 0.8 to 5.2 mierograms/niL. She responded to a reduetion in the warfarin dosage to 2 mg daily. The authors of the report also say that they have seen 4 other... 

These reports seem to be the only ones to describe this interaction so the interaction is not yet established. However it would seem prudent to monitor the effects if interferon is given to patients taking coumarins, reducing the dosage if necessary. For a case of decreased warfarin effects in a patient given interferon alfa-2b and ribavirin, see Coumarins + Ribavirin , p.447. 

Systematic reviews In a systematic review of antiviral drug therapy in 16 studies, in which pegylated interferon alfa was used in combination with ribavirin for recurrent hepatitis C after liver transplantation, the mean sustained viral response rate was 30% (range 8-50%) [34 ]. Dosage reduction and withdrawal of treatment were common (73% and 28% respectively). 

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