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Hytrin (Terazosin Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Use with Other Drugs

In a study (n=24) where terazosin and verapamil were administered concomitantly, terazosin’s mean AUC0-24 increased 11% after the first verapamil dose and after 3 weeks of verapamil treatment it increased by 24% with associated increases in Cmax (25%) and Cmin (32%) means. Terazosin mean Tmax decreased from 1.3 hours to 0.8 hours after 3 weeks of verapamil treatment. Statistically significant differences were not found in the verapamil level with and without terazosin. In a study (n=6) where terazosin and captopril were administered concomitantly, plasma disposition of captopril was not influenced by concomitant administration of terazosin and terazosin maximum plasma concentrations increased linearly with dose at steady-state after administration of terazosin plus captopril (see DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

HYTRIN was devoid of mutagenic potential when evaluated in vivo and in vitro (the Ames test, in vivo cytogenetics, the dominant lethal test in mice, in vivo Chinese hamster chromosome aberration test and V79 forward mutation assay).

HYTRIN, administered in the feed to rats at doses of 8, 40, and 250 mg/kg/day (70, 350, and 2100 mg/M2/day), for two years, was associated with a statistically significant increase in benign adrenal medullary tumors of male rats exposed to the 250 mg/kg dose. This dose is 175 times the maximum recommended human dose of 20 mg (12 mg/M2). Female rats were unaffected. HYTRIN was not oncogenic in mice when administered in feed for 2 years at a maximum tolerated dose of 32 mg/kg/day (110 mg/M2; 9 times the maximum recommended human dose). The absence of mutagenicity in a battery of tests, of tumorigenicity of any cell type in the mouse carcinogenicity assay, of increased total tumor incidence in either species, and of proliferative adrenal lesions in female rats, suggests a male rat species-specific event. Numerous other diverse pharmaceutical and chemical compounds have also been associated with benign adrenal medullary tumors in male rats without supporting evidence for carcinogenicity in man.

The effect of HYTRIN on fertility was assessed in a standard fertility/reproductive performance study in which male and female rats were administered oral doses of 8, 30 and 120 mg/kg/day. Four of 20 male rats given 30 mg/kg (240 mg/M2; 20 times the maximum recommended human dose), and five of 19 male rats given 120 mg/kg (960 mg/M2; 80 times the maximum recommended human dose), failed to sire a litter. Testicular weights and morphology were unaffected by treatment. Vaginal smears at 30 and 120 mg/kg/day, however, appeared to contain less sperm than smears from control matings and good correlation was reported between sperm count and subsequent pregnancy.

Oral administration of HYTRIN for one or two years elicited a statistically significant increase in the incidence of testicular atrophy in rats exposed to 40 and 250 mg/kg/day (29 and 175 times the maximum recommended human dose), but not in rats exposed to 8 mg/kg/day (> 6 times the maximum recommended human dose). Testicular atrophy was also observed in dogs dosed with 300 mg/kg/day (> 500 times the maximum recommended human dose) for three months but not after one year when dosed with 20 mg/kg/day (38 times the maximum recommended human dose). This lesion has also been seen with Minipress®, another (marketed) selective-alpha-1 blocking agent.

Pregnancy

Teratogenic Effects

Pregnancy Category C

HYTRIN was not teratogenic in either rats or rabbits when administered at oral doses up to 280 and 60 times, respectively, the maximum recommended human dose. Fetal resorptions occurred in rats dosed with 480 mg/kg/day, approximately 280 times the maximum recommended human dose. Increased fetal resorptions, decreased fetal weight and an increased number of supernumerary ribs were observed in offspring of rabbits dosed with 60 times the maximum recommended human dose. These findings (in both species) were most likely secondary to maternal toxicity. There are no adequate and well-controlled studies in pregnant women and the safety of terazosin in pregnancy has not been established. HYTRIN is not recommended during pregnancy unless the potential benefit justifies the potential risk to the mother and fetus.

OVERDOSAGE

Should overdosage of HYTRIN lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that HYTRIN is highly protein bound; therefore, dialysis may not be of benefit.

CONTRAINDICATIONS

HYTRIN tablets are contraindicated in patients known to be hypersensitive to terazosin hydrochloride.

REFERENCE

  1. Lepor H. Role of alpha-adrenergic blockers in the treatment of benign prostatic hypertrophy. Prostate 1990; 3:75-84.

Abbott Laboratories

North Chicago, IL 60064, U.S.A.

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