Safety and Tolerance of Combination Therapy

The safety and tolerability of combination therapy have recently been reviewed in detail by Maddrey (81). The safety and tolerance of the combination of IFN and ribavirin is similar to those treated with IFN alone.

Ribavirin predictably causes hemolysis at currently recommended doses. The mean fall in hemoglobin (Hb) is 2-3 gm/dL, and this occurs during the first 4 wk of treatment, remains relatively stable thereafter, and returns to baseline within 4 wk of stopping treatment (33,45,50). Although only about 5% of patients develop Hb levels less than 9.6 gm/ dL, rapid and significant drops may occur in a short period of time, and therefore careful monitoring is required during the first few weeks of combination therapy. The fall in Hb is accompanied by a reticulocytosis. Recombinant erythropoietin has been shown to increase Hb levels back to near baseline, despite continuation of treatment, and may be useful in selected patients who become profoundly or symptomatically anemic (82). Decreases in white blood cell and neutrophil are similar to those with the decline with IFN alone. Likewise, platelet counts decline, whether or not ribavirin is added to the regimen, but the decrease is less in those receiving ribavirin, which is probably the result of a relative reactive throm-bocytosis resulting from anemia.

Most clinical trials have shown that the addition of ribavirin to the treatment regimen of chronic hepatitis does not increase clinically perceived side effects of treatment (33,45,50). However, many patients complain of more intense flu-like side effects when receiving combination treatment. Discontinuation of treatment is more common in those receiving both drugs than with IFN alone (9 vs 5%). The most common reason for dose reduction or interruption is anemia and resulting fatigue (33,45,50).

Clearly, from the side effect profile of ribavirin, that combination therapy is not indicated for every patient. It should be used with great caution, or not at all, in patients with pre-existing anemia or hemolytic disorders, coronary artery disease, or hypoxia. Careful consideration should be given to the potential effects of an acute anemia in each patient in whom combination treatment is considered. Because of the potential for teratogenic and embryotoxic effects in animals, it should not be used in patients of child-bearing potential, unless adequate contraception is assured. Trial and postmarketing surveillance data suggests that most patients or spouses of patients who become pregnant during or within 6 mo after treatment will spontaneously abort, if the pregnancy is not otherwise terminated, but one fetal anomaly has been observed (Davis, unpublished data).

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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