Terazosin

Description

DESCRIPTION Terazosin hydrochloride, an alpha-1-selective adrenoceptor blocking agent, is a quinazoline derivative represented by the following chemical name,molecular formula and structural formula: (RS)-Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-[(tetrahydro-2-furanyl)carbonyl]-, monohydrochloride.C 19 H 26 ClN 5 O 4 Terazosin hydrochloride is a white, crystalline substance, freely soluble in water and isotonic saline and has a molecular weight of 423.93. Each capsule, for oral administration, contains 1 mg, 2 mg, 5 mg or 10 mg of terazosin as terazosin hydrochlolde. In addition, each capsule contains the following inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, and pregelatinized starch. The gelatin capsule contains gelatin, silicon dioxide, sodium lauryl sulfate, and titanium dioxide. The 1 mg shell also contains black iron oxide; the 2 mg capsule shell also contains D&C Yellow #10; the 5 mg capsule shell also contains D&C Yellow #10, FD&C Red #40 and D&C Red #28; the 10 mg capsule shell also contains FD&C Green #3 and D&C Yellow#10. Terazosin Hydrochloride Chemical Structure

What Is Terazosin Used For?

INDICATIONS AND USAGE Terazosin capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH). There is a rapid response, with approximately 70% of patients experiencing an increase in urinary flow and improvement in symptoms of BPH when treated with terazosin capsules. The long-term effects of terazosin capsules on the incidence of surgery, acute urinary obstruction or other complications of BPH are yet to be determined. Terazosin capsules are also indicated for the treatment of hypertension. Terazosin capsules can be used alone or in combination with other antihypertensive agents such as diuretics or beta-adrenergic blocking agents.

Dosage and Administration

DOSAGE AND ADMINISTRATION If terazosin capsules administration is discontinued for several days, therapy should be reinstituted using the initial dosing regimen. Benign Prostatic Hyperplasia Initial Dose : 1 mg at bedtime is the starting dose for all patients, and this dose should not be exceeded as an initial dose. Patients should be closely followed during initial administration in order to minimize the risk of severe hypotensive response. Subsequent Doses : The dose should be increased in a stepwise fashion to 2 mg, 5 mg, or 10 mg once daily to achieve the desired improvement of symptoms and/or flow rates. Doses of 10 mg once daily are generally required for the clinical response. Therefore, treatment with 10 mg for a minimum of 4 to 6 weeks may be required to assess whether a beneficial response has been achieved. Some patients may not achieve a clinical response despite appropriate titration. Although some additional patients responded at a 20 mg daily dose, there was an insufficient number of patients studied to draw definitive conclusions about this dose. There are insufficient data to support the use of higher doses for those patients who show inadequate or no response to 20 mg daily. If terazosin administration is discontinued for several days or longer, therapy should be reinstituted using the initial dosing regimen. Use With Other Drugs : Caution should be observed when terazosin capsules are administered concomitantly with other antihypertensive agents, especially the calcium channel blocker verapamil, to avoid the possibility of developing significant hypotension. When using terazosin capsules and other antihypertensive agents concomitantly, dosage reduction and retitration of either agent may be necessary (see PRECAUTIONS ). Hypotension has been reported when terazosin capsules have been used with phosphodiesterase-5 (PDE-5) inhibitors. Hypertension The dose of terazosin capsules and the dose interval (12 or 24 hours) should be adjusted according to the patient’s individual blood pressure response. The following is a guide to its administration: Initial Dose 1 mg at bedtime is the starting dose for all patients, and this dose should not be exceeded. This initial dosing regimen should be strictly observed to minimize the potential for severe hypotensive effects. Subsequent Doses The dose may be slowly increased to achieve the desired blood pressure response. The usual recommended dose range is 1 mg to 5 mg administered once a day; however, some patients may benefit from doses as high as 20 mg per day. Doses over 20 mg do not appear to provide further blood pressure effect and doses over 40 mg have not been studied. Blood pressure should be monitored at the end of the dosing interval to be sure control is maintained throughout the interval. It may also be helpful to measure blood pressure 2 to 3 hours after dosing to see if the maximum and minimum responses are similar, and to evaluate symptoms such as dizziness or palpitations which...

Side Effects (Adverse Reactions)

ADVERSE REACTIONS Benign Prostatic Hyperplasia The incidence of treatment-emergent adverse events has been ascertained from clinical trials conducted worldwide. All adverse events reported during these trials were recorded as adverse reactions. The incidence rates presented below are based on combined data from six placebo-controlled trials involving once-a-day administration of terazosin at doses ranging from 1 to 20 mg. Table 1 summarizes those adverse events reported for patients in these trials when the incidence rate in the terazosin group was at least 1%, and was greater than that for the placebo group, or where the reaction is of clinical interest. Asthenia, postural hypotension, dizziness, somnolence, nasal congestion/rhinitis, and impotence were the only events that were significantly (p ≤ 0.05) more common in patients receiving terazosin than in patients receiving placebo. The incidence of urinary tract infection was significantly lower in the patients receiving terazosin than in patients receiving placebo. An analysis of the incidence rate of hypotensive adverse events (see PRECAUTIONS ) adjusted for the length of drug treatment has shown that the risk of the events is greatest during the initial seven days of treatment, but continues at all time intervals. TABLE 1. Adverse Reactions During Placebo-Controlled Trials Benign Prostatic Hyperplasia Body System Terazosin (N = 636) Placebo (N = 360) BODY AS A WHOLE Includes weakness, tiredness, lassitude, and fatigue. Asthenia Flu Syndrome Headache 7.4% p ≤ 0.05 comparison between groups. 2.4% 4.9% 3.3% 1.7% 5.8% CARDIOVASCULAR SYSTEM Hypotension Palpitations Postural Hypotension Syncope 0.6% 0.9% 3.9% 0.6% 0.6% 1.1% 0.8% 0.0% DIGESTIVE SYSTEM Nausea 1.7% 1.1% METABOLIC AND NUTRITIONAL DISORDERS Peripheral Edema Weight Gain 0.9% 0.5% 0.3% 0.0% NERVOUS SYSTEM Dizziness Somnolence Vertigo 9.1% 3.6% 1.4% 4.2% 1.9% 0.3% RESPIRATORY SYSTEM Dyspnea Nasal Congestion/Rhinitis 1.7% 1.9% 0.8% 0.0% SPECIAL SENSES Blurred Vision/Amblyopia 1.3% 0.6% UROGENITAL SYSTEM Impotence Urinary Tract Infection 1.6% 1.3% 0.6% 3.9% Additional adverse events have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to terazosin. The safety profile of patients treated in the long-term open-label study was similar to that observed in the controlled studies. The adverse events were usually transient and mild or moderate in intensity, but sometimes were serious enough to interrupt treatment. In the placebo-controlled clinical trials, the rates of premature termination due to adverse events were not statistically different between the placebo and terazosin groups. The adverse events that were bothersome, as judged by their being reported as reasons for discontinuation of therapy by at least 0.5% of the terazosin group and being reported more often than in the placebo group, are shown in Table 2. TABLE 2. Discontinuation During Placebo-Controlled Trials Benign Prostatic Hyperplasia Body System Terazosin (N = 636) Placebo (N = 360) BODY AS A WHOLE Fever Headache 0.5% 1.1% 0.0% 0.8% CARDIOVASCULAR SYSTEM Postural Hypotension Syncope 0.5% 0.5% 0.0% 0.0% DIGESTIVE SYSTEM Nausea 0.5% 0.3% NERVOUS SYSTEM Dizziness Vertigo 2.0% 0.5% 1.1% 0.0% RESPIRATORY SYSTEM Dyspnea 0.5% 0.3% SPECIAL SENSES Blurred Vision/Amblyopia 0.6% 0.0% UROGENITAL SYSTEM Urinary Tract Infection 0.5% 0.3% Hypertension The prevalence of adverse reactions has been ascertained from clinical trials conducted primarily in the United States. All adverse experiences (events) reported during these trials were recorded as adverse reactions. The prevalence rates presented below are based on combined data from fourteen placebo-controlled trials involving once-a-day administration of terazosin, as monotherapy or in combination with other antihypertensive agents, at doses ranging from 1 to 40 mg. Table 3 summarizes those adverse experiences reported for patients in these...

Drug Interactions

Drug Interactions In controlled trials, terazosin have been added to diuretics, and several beta-adrenergic blockers; no unexpected interactions were observed. Terazosin has also been used in patients on a variety of concomitant therapies; while these were not formal interaction studies, no interactions were observed. Terazosin has been used concomitantly in at least 50 patients on the following drugs or drug classes: analgesic/anti-inflammatory (e.g., acetaminophen, aspirin, codeine, ibuprofen, indomethacin); antibiotics (e.g., erythromycin, trimethoprim and sulfamethoxazole); anticholinergic/sympathomimetics (e.g., phenylephrine hydrochloride, phenylpropanolamine hydrochloride, pseudoephedrine hydrochloride); antigout (e.g., allopurinol); antihistamines (e.g., chlorpheniramine); cardiovascular agents (e.g., atenolol, hydrochlorothiazide, methyclothiazide, propranolol); corticosteroids; gastrointestinal agents (e.g., antacids); hypoglycemics; sedatives and tranquilizers (e.g., diazepam).

Contraindications

CONTRAINDICATIONS Terazosin capsules are contraindicated in patients known to be hypersensitive to terazosin hydrochloride.

Pregnancy and Breastfeeding

Pregnancy Teratogenic Effects : Pregnancy Category C Terazosin capsules were 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. Terazosin capsules are not recommended during pregnancy unless the potential benefit justifies the potential risk to the mother and fetus. Nonteratogenic Effects : In a peri- and post-natal development study in rats, significantly more pups died in the group dosed with 120 mg/kg/day (> 75 times the maximum recommended human dose) than in the control group during the three-week postpartum period.

Nursing Mothers : It is not known whether terazosin is excreted in breast milk. Because many drugs are excreted in breast milk, caution should be exercised when terazosin capsules are administered to a nursing woman.

Overdosage

OVERDOSAGE Should overdosage of terazosin capsules 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 terazosin is 90-94% protein bound; therefore, dialysis may not be of benefit.

How Supplied

HOW SUPPLIED Terazosin Capsules are available in four dosage strengths: 1 mg Terazosin Capsules, USP are available as Size 3 iron gray opaque capsules printed "TL 383" axially in black ink on body and cap. Bottles of 90: NDC 59746-383-90 Bottles of 100: NDC 59746-383-06 Bottles of 500: NDC 59746-383-09 Bottles of 1000: NDC 59746-383-10 2 mg Terazosin Capsules, USP are available as Size 3 ivory opaque capsules printed "TL 384" axially in black ink on body and cap. Bottles of 90: NDC 59746-384-90 Bottles of 100: NDC 59746-384-06 Bottles of 500: NDC 59746-384-09 Bottles of 1000: NDC 59746-384-10 5 mg Terazosin Capsules, USP are available as Size 3 orange opaque capsules printed "TL 385" axially in black ink on body and cap. Bottles of 90: NDC 59746-385-90 Bottles of 100: NDC 59746-385-06 Bottles of 500: NDC 59746-385-09 Bottles of 1000: NDC 59746-385-10 10 mg Terazosin Capsules, USP are available as Size 3 light green opaque capsules printed "TL 386" axially in black ink on body and cap. Bottles of 90: NDC 59746-386-90 Bottles of 100: NDC 59746-386-06 Bottles of 500: NDC 59746-386-09 Bottles of 1000: NDC 59746-386-10 Dispense in a tight, light-resistant container as defined in the USP. Recommended storage: Store at 20 to 25°C (68 to 77°F) [see USP Controlled Room Temperature]. Protect from light and moisture. Rx only Revised 01/2018 Jubilant Cadista Pharmaceuticals Inc. Salisbury, MD 21801, USA For additional copies of the printed patient information/medication guide, please visit www.cadista.com or call 1-800-313-4623.