Safety assessment of terazosin in thetreatment of patients with symptomatic benign prostatic hyperplasia: A combined analysis

doi:10.1016/S0090-4295(94)80008-1

Urology

Volume 44, Issue 1, July 1994, Pages 46-51

https://doi.org/10.1016/S0090-4295(94)80008-1 Get rights and content

Abstract

Objectives

This study reviews and assesses the safety of terazosin for thetreatment of symptomatic benign prostatic hyperplasia (BPH).

Methods.

Six placebo-controlled trials (including two unpublished series) involving 996patients provide the database for this evaluation. Six hundred thirty-six patients received terazosin from 1 to 20 mg daily for a total of 229 patient-years of exposure to terazosin. The most common final dose of terazosin was 10 mg once daily.

Results

Side effects were generally mild or moderate in severity and resolved following cessation of therapy. Side effects resulted in premature withdrawal in 9% of terazosin-treated patients and 7% of placebo-treated patients (difference not significant). Dizziness (2.0%) and headache (1.1 %) were the most common symptoms leading to premature withdrawal from the studies. Although postural symptoms and dizziness were slightly more common in those terazosin-treated patients 65 or more years old compared with patients less than 65 years old, this difference was not statistically significant. Only 4 of the 636 patients (0.6%) had syncopal episodes; 2 of these occurred at initiation of terazosin therapy or at dose escalation. Minimal reductions in blood pressure were observed in normotensive patients and patients with hypertension controlled by concomitant medication, whereas patients with untreated hypertension had substantial decreases in both systolic and diastolic blood pressures. Statistically significant increases in high density lipoprotein to cholesterol ratio and reductions in total cholesterol, low density lipoprotein, and triglycerides were also seen.

Conclusions.

This combined analysis suggests that terazosin can be safely administered to both normotensive and hypertensive patients with symptomatic BPH.

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Cited by (65)

Time Course of Incident Adverse Experiences Associated with Doxazosin, Finasteride and Combination Therapy in Men with Benign Prostatic Hyperplasia: The MTOPS Trial
2016, Journal of Urology
Citation Excerpt :
Previous studies have shown variable incidences of sexual AEs with α-blocker BPH medical therapies. An assessment of safety data from 6 BPH studies ranging in duration from 2 to 6 months indicated that the incidence of erectile dysfunction was 2% for terazosin compared to 1% for placebo.12 In another pooled analysis of adverse event reports from 7 double-blind, placebo controlled terazosin clinical trials 2 months to 1 year in duration abnormal ejaculation was reported in 1% of men treated with terazosin compared with 0.3% treated with placebo (p <0.01).13
We examined first (incident) reports of selected adverse experiences associated with medical therapy in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia.
We studied the 6 most common adverse experiences, including nonsexual function related experiences (dizziness, orthostatic hypotension and weakness) and sexual function related experiences (impotence, decreased libido and abnormal ejaculation) reported in the MTOPS (Medical Therapy of Prostatic Symptoms) Study. A total of 3,047 men were randomized to placebo, doxazosin, finasteride or combination therapy and followed for a mean duration of 4.5 years. We compared the incidence rates of adverse experiences at year 1 to the rates thereafter.
For each assigned treatment group, the incidence rates were significantly higher for all 6 adverse experiences examined at year 1 compared with the rates thereafter. Men assigned to combination therapy experienced the highest rates at year 1 with rates 3.4-fold to 10.6-fold higher than rates after year 1. The incidence rates for orthostatic hypotension and dizziness were significantly higher in the doxazosin and combination therapy groups compared with the placebo group at year 1. The incidence rates of the 3 examined sexual function related adverse experiences were significantly higher in the finasteride and combination therapy groups than in the placebo group at year 1.
Rates of the first report of sexual function related and other adverse experiences associated with doxazosin, finasteride and combination therapy were greatest during year 1 of treatment. These patterns should be considered by patients and physicians when treatment for lower urinary tract function is initiated with these drugs.
Pharmacologic complications
2009, Complications of Urologic Surgery: Expert Consult
Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line
2009, Cancer Letters
Citation Excerpt :
But the reported IC50 of terazosin on prostate cancer cells is higher than 100 μM (about 46 μg/ml) [12,13,19]. We used lower and nontoxic dosage of terazosin (1 μg/ml) to decrease adverse effects [41–43], and in combination with 5 μg/ml of genistein to produce more effective anticancer results suggesting that this combination strategy would be an attractive clinical option. Many anticancer agents and DNA-damaging agents arrest the cell cycle at G1, S, or G2/M phase and induce apoptotic cell death [44–49].
Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective α1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an α1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145.
Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 μg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 μg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-X_L, and of VEGF₁₆₅ and VEGF₁₂₁ than genistein alone.
In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.
A review of combination therapy in patients with benign prostatic hyperplasia
2007, Clinical Therapeutics
Trials of monotherapy with α₁-adrenergic-receptor antagonists (α₁ARAs) and 5a-reductase inhibitors (5ARIs) have found that the former drug class is effective in managing benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and improving the maximal urinary flow rate in shortand long-term treatment, regardless of prostate size, whereas the latter drug class is effective in reducing prostate size and preventing disease progression in longer-term treatment. The differing mechanisms of action and areas of efficacy of these 2 drug classes make them promising candidates for combination therapy.
This article reviews key trials of monotherapy and combination α₁ARV5ARI therapy in the treatment and prevention of BPH-related voiding dysfunction.
MEDLINE (1976–2006) and the Cochrane Central Register of Controlled Trials (1976–2006) were searched for relevant clinical trials and reviews using the terms benign prostatic byperplasia, lower urinary tract symptoms, LUTS, α-adrenergic-receptor antagonists, α-blockers, 5α-reductase inbibitors, combination therapy, MTOPS, SMART, PREDICT, adverse events, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, and finasteride. Abstracts from selected professional conferences also were reviewed.
Three previous trials of α₁ARA/5ARI therapy found no therapeutic benefit for combination therapy relative to monotherapy, but their conclusions were limited to some extent by their designs, particularly the duration of treatment. Data from the Medical Therapy of Prostatic Symptoms (MTOPS) study, however, indicated a potential role for long-term use of α₁ARA/5ARI therapy, particularly in patients with greater symptom severity (mean score of 17 on the American Urological Association symptom index), larger prostate volume (mean, 32 g), and higher prostate-specific antigen (PSA) levels (>1.5 ng/mL) at baseline. In the MTOPS study, combination therapy with the α₁ARA doxazosin and the SARI finasteride was significantly more effective than either component alone in reducing BPH-related symptoms (P = 0.006 vs doxazosin monotherapy; P < 0.001 vs finasteride monotherapy) and lowering the rate of overall clinical progression (P < 0.001 vs either monotherapy). In addition, there are data from a subgroup analysis of MTOPS suggesting that the presence of prostatic inflammation may indicate a greater likelihood of treatment efficacy with combination α₁ARA/5ARI therapy.
The available data suggest that combination α₁ARA/5ARI therapy is beneficial in the treatment of BPH and the associated symptoms. The greatest efficacy was evident in patients with an enlarged prostate, more severe symptoms, and higher PSA levels. There are limited data suggesting that the presence of prostatic inflammation may indicate a greater likelihood of treatment efficacy with combination therapy.
Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia
2003, Urology
To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo.
The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded.
At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P <0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively.
Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy.
Hepatotoxicity induced by terazosin [3]
2003, Medicina Clinica

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^*: This research was supported by a grant from Abbott Laboratories, Abbott Park, Illinois.

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Adult urologySafety assessment of terazosin in thetreatment of patients with symptomatic benign prostatic hyperplasia: A combined analysis*

Abstract

Objectives

Methods.

Results

Conclusions.

J Urol

J Urol

J Urol

J Urol

J Urol

The use of alpha-blockers in the a ngement of benign prostatic hyperplasia

NY State J Med

Alpha-blockade in the management of benign prostatic hyperplasia

Alpha-adrenergic blockers in prostatism

Br J Surg

The use of alphadrenergic blockers in benign prostatic obstruction

Br J Urol

A placebo-controlled double-blind study of the effect of phenoxybenzami in benign prostatic obstruction

Br J Urol

Bladder outflow obstruction treated with phenoxybenzamine

Br J

Adult urology
Safety assessment of terazosin in thetreatment of patients with symptomatic benign prostatic hyperplasia: A combined analysis*