Dental and Periodontal Disorders
Dental and periodontal disorders have been reported in patients receiving ribavirin and interferon combination therapy. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the combination of REBETOL and interferon alfa-2b. Patients should brush their teeth thoroughly twice daily and have regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they should be advised to rinse out their mouth thoroughly afterwards.
In addition to those tests normally required for monitoring patients, the following laboratory tests are recommended for all patients on INTRON A therapy, prior to beginning treatment and then periodically thereafter.
- Standard hematologic tests - including hemoglobin, complete and differential white blood cell counts, and platelet count
- Blood chemistries - electrolytes, liver function tests, and TSH
Those patients who have preexisting cardiac abnormalities and/or are in advanced stages of cancer should have electrocardiograms taken prior to and during the course of treatment.
Mild to moderate leukopenia and elevated serum liver enzyme (SGOT) levels have been reported with intralesional administration of INTRON A (see ADVERSE REACTIONS); therefore, the monitoring of these laboratory parameters should be considered.
Baseline chest X-rays are suggested and should be repeated if clinically indicated.
For malignant melanoma patients, differential WBC count and liver function tests should be monitored weekly during the induction phase of therapy and monthly during the maintenance phase of therapy.
For specific recommendations in chronic hepatitis C and chronic hepatitis B, see INDICATIONS AND USAGE.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies with INTRON A have not been performed to determine carcinogenicity.
Interferon may impair fertility. In studies of interferon administration in nonhuman primates, menstrual cycle abnormalities have been observed. Decreases in serum estradiol and progesterone concentrations have been reported in women treated with human leukocyte interferon.12 Therefore, fertile women should not receive INTRON A therapy unless they are using effective contraception during the therapy period. INTRON A therapy should be used with caution in fertile men.
Mutagenicity studies have demonstrated that INTRON A is not mutagenic.
Studies in mice (0.1, 1.0 million IU/day), rats (4, 20, 100 million IU/kg/day), and cynomolgus monkeys (1.1 million IU/kg/day; 0.25, 0.75, 2.5 million IU/kg/day) injected with INTRON A for up to 9 days, 3 months, and 1 month, respectively, have revealed no evidence of toxicity. However, in cynomolgus monkeys (4, 20, 100 million IU/kg/day) injected daily for 3 months with INTRON A toxicity was observed at the mid and high doses and mortality was observed at the high dose.
However, due to the known species-specificity of interferon, the effects in animals are unlikely to be predictive of those in man.
INTRON A in combination with REBETOL should be used with caution in fertile men. See REBETOL package insert for additional information.
Pregnancy Category C
INTRON A has been shown to have abortifacient effects in Macaca mulatta (rhesus monkeys) at 15 and 30 million IU/kg (estimated human equivalent of 5 and 10 million IU/kg, based on body surface area adjustment for a 60-kg adult). There are no adequate and well-controlled studies in pregnant women. INTRON A therapy should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category X applies to combination treatment with INTRON A and REBETOL (see CONTRAINDICATIONS). See REBETOL package insert for additional information. Significant teratogenic and/or embryocidal effects have been demonstrated in all animals species exposed to ribavirin. REBETOL therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. See CONTRAINDICATIONS and the REBETOL package insert.
Ribavirin Pregnancy Registry: A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment and for 6-months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.