d tranquilizers (e.g., diazepam).

a 1 mg dose of terazosin, given at bedtime. the 2 mg, 5 mg and 10 mg capsules are not indicated as initial therapy. dosage should then be increased slowly, according to recommendations in the dosage and administration section and additional antihypertensive agents should be added with caution. the patient should be cautioned to avoid situations, such as driving or hazardous tasks, where injury could result should syncope occur during initiation of therapy. in early investigational studies, where increasing single doses up to 7.5 mg were given at 3 day intervals, tolerance to the first dose phenomenon did not necessarily develop and the "first dose" effect could be observed at all doses. syncopal episodes occurred in 3 of the 14 subjects given terazosin at doses of 2.5, 5 and 7.5 mg, which are higher than the recommended initial dose; in addition, severe orthostatic hypotension (blood pressure falling to 50/0 mmhg) was seen in two others and dizziness, tachycardia, and lightheadedness occurred in most subjects. these adverse effects all occurred within 90 minutes of dosing. in three placebo-controlled bph studies 1, 2, and 3 (see clinical pharmacology ), the incidence of postural hypotension in the terazosin treated patients was 5.1%, 5.2%, and 3.7% respectively. in multiple dose clinical trials involving nearly 2000 hypertensive patients treated with terazosin, syncope was reported in about 1% of patients. syncope was not necessarily associated only with the first dose. if syncope occurs, the patient should be placed in a recumbent position and treated supportively as necessary. there is evidence that the orthostatic effect of terazosin is greater, even in chronic use, shortly after dosing. the risk of the events is greatest during the initial seven days of treatment, but continues at all time intervals. priapism rarely, (probably less than once in every several thousand patients), terazosin and other α 1 – antagonists have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). two or three dozen cases have been reported. because this condition can lead to permanent impotence if not promptly treated, patients must be advised about the seriousness of the condition (see precautions, information for patients ).

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 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 can result from excessive hypotensive response. if response is substantially diminished at 24 hours an increased dose or use of a twice daily regimen can be considered. if terazosin administration is discontinued for several days or longer, therapy should be reinstituted using the initial dosing regimen. in clinical trials, except for the initial dose, the dose was given in the morning. use with other drugs (see above).

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. 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. 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 trials where the prevalence rate in the terazosin group was at least 5%, where the prevalence rate for the terazosin group was at least 2% and was greater than the prevalence rate for the placebo group, or where the reaction is of particular interest. asthenia, blurred vision, dizziness, nasal congestion, nausea, peripheral edema, palpitations and somnolence were the only symptoms that were significantly (p < 0.05) more common in patients receiving terazosin than in patients receiving placebo. similar adverse reaction rates were observed in placebo-controlled monotherapy trials. additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to terazosin. the following additional adverse reactions were reported by at least 1% of 1987 patients who received terazosin in controlled or open, short- or long-term clinical trials or have been reported during marketing experience: body as a whole chest pain, facial edema, fever, abdominal pain, neck pain, shoulder pain cardiovascular system arrhythmia, vasodilation digestive system constipation, diarrhea, dry mouth, dyspepsia, flatulence, vomiting metabolic/nutritional disorders gout musculoskeletal system arthralgia, arthritis, joint disorder, myalgia nervous system anxiety, insomnia respiratory system bronchitis, cold symptoms, epistaxis, flu symptoms, increased cough, pharyngitis, rhinitis skin and appendages pruritus, rash, sweating special senses abnormal vision, conjunctivitis, tinnitus urogenital system urinary frequency, urinary incontinence primarily reported in postmenopausal women, urinary tract infection. the adverse reactions were usually mild or moderate in intensity but sometimes were serious enough to interrupt treatment. the adverse reactions that were most 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 4. post-marketing experience post-marketing experience indicates that in rare instances patients may develop allergic reactions, including anaphylaxis, following administration of terazosin hydrochloride. there have been reports of priapism and thrombocytopenia during post-marketing surveillance. atrial fibrillation has been reported. during cataract surgery, a variant of small pupil syndrome known as intraoperative floppy iris syndrome (ifis) has been reported in association with alpha-1 blocker therapy (see precaution s). to report suspected adverse reactions, contact avet pharmaceuticals inc. at 1-866-901-drug (3784) or fda at 1-800-fda-1088 or www.fda.gov/medwatch. image image image image

d tranquilizers (e.g., diazepam).

by blockade of alpha-1 adrenoceptors in the bladder neck and prostate. because there are relatively few alpha-1 adrenoceptors in the bladder body, terazosin is able to reduce the bladder outlet obstruction without affecting bladder contractility. terazosin has been studied in 1222 men with symptomatic bph. in three placebo-controlled studies, symptom evaluation and uroflowmetric measurements were performed approximately 24 hours following dosing. symptoms were quantified using the boyarsky index. the questionnaire evaluated both obstructive (hesitancy, intermittency, terminal dribbling, impairment of size and force of stream, sensation of incomplete bladder emptying) and irritative (nocturia, daytime frequency, urgency, dysuria) symptoms by rating each of the 9 symptoms from 0 to 3, for a total score of 27 points. results from these studies indicated that terazosin statistically significantly improved symptoms and peak urine flow rates over placebo as follows: in all three studies, both symptom scores and peak urine flow rates showed statistically significant improvement from baseline in patients treated with terazosin from week 2 (or the first clinic visit) and throughout the study duration. analysis of the effect of terazosin on individual urinary symptoms demonstrated that compared to placebo, terazosin significantly improved the symptoms of hesitancy, intermittency, impairment in size and force of urinary stream, sensation of incomplete emptying, terminal dribbling, daytime frequency and nocturia. global assessments of overall urinary function and symptoms were also performed by investigators who were blinded to patient treatment assignment. in studies 1 and 3, patients treated with terazosin had a significantly (p ≤ 0.001) greater overall improvement compared to placebo treated patients. in a short term study (study 1), patients were randomized to either 2, 5 or 10 mg of terazosin or placebo. patients randomized to the 10 mg group achieved a statistically significant response in both symptoms and peak flow rate compared to placebo (figure 1). in a long-term, open-label, non-placebo controlled clinical trial, 181 men were followed for 2 years and 58 of these men were followed for 30 months. the effect of terazosin on urinary symptom scores and peak flow rates was maintained throughout the study duration (figures 2 and 3): in this long-term trial, both symptom scores and peak urinary flow rates showed statistically significant improvement suggesting a relaxation of smooth muscle cells. although blockade of alpha-1 adrenoceptors also lowers blood pressure in hypertensive patients with increased peripheral vascular resistance, terazosin treatment of normotensive men with bph did not result in a clinically significant blood pressure lowering effect: b. hypertension in animals, terazosin causes a decrease in blood pressure by decreasing total peripheral vascular resistance. the vasodilatory hypotensive action of terazosin appears to be produced mainly by blockade of alpha-1-adrenoceptors. terazosin decreases blood pressure gradually within 15 minutes following oral administration. patients in clinical trials of terazosin were administered once daily (the great majority) and twice daily regimens with total doses usually in the range of 5 to 20 mg/day, and had mild (about 77%, diastolic pressure 95 to 105 mmhg) or moderate (23%, diastolic pressure 105 to 115 mmhg) hypertension. because terazosin, like all alpha antagonists, can cause unusually large falls in blood pressure after the first dose or first few doses, the initial dose was 1 mg in virtually all trials, with subsequent titration to a specified fixed dose or titration to some specified blood pressure end point (usually a supine diastolic pressure of 90 mmhg). blood pressure responses were measured at the end of the dosing interval (usually 24 hours) and effects were shown to persist throughout the interval, with the usual supine responses 5 to 10 mmhg systolic and 3.5 to 8 mmhg diastolic greater than placebo. the responses in the standing position tended to be somewhat larger, by 1 to 3 mmhg, although this was not true in all studies. the magnitude of the blood pressure responses was similar to prazosin and less than hydrochlorothiazide (in a single study of hypertensive patients). in measurements 24 hours after dosing, heart rate was unchanged. limited measurements of peak response (2 to 3 hours after dosing) during chronic terazosin administration indicate that it is greater than about twice the trough (24 hour) response, suggesting some attenuation of response at 24 hours, presumably due to a fall in blood terazosin concentrations at the end of the dose interval. this explanation is not established with certainty, however, and is not consistent with the similarity of blood pressure response to once daily and twice daily dosing and with the absence of an observed dose-response relationship over a range of 5 to 20 mg, i.e., if blood concentrations had fallen to the point of providing less than full effect at 24 hours, a shorter dosing interval or larger dose should have led to increased response. further dose response and dose duration studies are being carried out. blood pressure should be measured at the end of the dose interval; if response is not satisfactory, patients may be tried on a larger dose or twice daily dosing regimen. the latter should also be considered if possibly blood pressure-related side effects, such as dizziness, palpitations, or orthostatic complaints, are seen within a few hours after dosing. the greater blood pressure effect associated with peak plasma concentrations (first few hours after dosing) appears somewhat more position-dependent (greater in the erect position) than the effect of terazosin at 24 hours and in the erect position there is also a 6 to 10 beat per minute increase in heart rate in the first few hours after dosing. during the first 3 hours after dosing 12.5% of patients had a systolic pressure fall of 30 mmhg or more from supine to standing, or standing systolic pressure below 90 mmhg with a fall of at least 20 mmhg, compared to 4% of a placebo group. there was a tendency for patients to gain weight during terazosin therapy. in placebo-controlled monotherapy trials, male and female patients receiving terazosin gained a mean of 1.7 and 2.2 pounds respectively, compared to losses of 0.2 and 1.2 pounds respectively in the placebo group. both differences were statistically significant. during controlled clinical trials, patients receiving terazosin monotherapy had a small but statistically significant decrease (a 3% fall) compared to placebo in total cholesterol and the combined low-density and very-low-density lipoprotein fractions. no significant changes were observed in high-density lipoprotein fraction and triglycerides compared to placebo. analysis of clinical laboratory data following administration of terazosin suggested the possibility of hemodilution based on decreases in hematocrit, hemoglobin, white blood cells, total protein and albumin. decreases in hematocrit and total protein have been observed with alpha-blockade and are attributed to hemodilution. pharmacokinetics terazosin hydrochloride administered as terazosin capsules is essentially completely absorbed in man. administration of capsules immediately after meals had a minimal effect on the extent of absorption. the time to reach peak plasma concentration however, was delayed by about 40 minutes. terazosin has been shown to undergo minimal hepatic first-pass metabolism and nearly all of the circulating dose is in the form of parent drug. the plasma levels peak about one hour after dosing, and then decline with a half-life of approximately 12 hours. in a study that evaluated the effect of age on terazosin pharmacokinetics, the mean plasma half-lives were 14 and 11.4 hours for the age group ≥ 70 years and the age group of 20 to 39 years, respectively. after oral administration the plasma clearance was decreased by 31.7% in patients 70 years of age or older compared to that in patients 20 to 39 years of age. the drug is 90 to 94% bound to plasma proteins and binding is constant over the clinically observed concentration range. approximately 10% of an orally administered dose is excreted as parent drug in the urine and approximately 20% is excreted in the feces. the remainder is eliminated as metabolites. impaired renal function had no significant effect on the elimination of terazosin, and dosage adjustment of terazosin to compensate for the drug removal during hemodialysis (approximately 10%) does not appear to be necessary. overall, approximately 40% of the administered dose is excreted in the urine and approximately 60% in the feces. the disposition of the compound in animals is qualitatively similar to that in man. image image image image image

nt over the clinically observed concentration range. approximately 10% of an orally administered dose is excreted as parent drug in the urine and approximately 20% is excreted in the feces. the remainder is eliminated as metabolites. impaired renal function had no significant effect on the elimination of terazosin, and dosage adjustment of terazosin to compensate for the drug removal during hemodialysis (approximately 10%) does not appear to be necessary. overall, approximately 40% of the administered dose is excreted in the urine and approximately 60% in the feces. the disposition of the compound in animals is qualitatively similar to that in man.

the body in black, packaged in bottles of 100 and 1000 capsules, ndc # 23155-738-01 and ndc # 23155-738-10. pharmacist: dispense in a tight, light-resistant container as defined in the usp, with a child-resistant closure (as required). store at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. protect from light and moisture distributed by: avet pharmaceuticals inc. east brunswick, nj 08816 1.866.901.drug (3784) revised: 08/2021 image