FDA label 41ee39bd-9a63-52c0-e054-00144ff8d46c

WARNINGS Syncope andFirst-doseEffect Terazosin capsules, like other alpha-adrenergic blocking agents, can cause marked lowering of blood pressure, especially postural hypotension, and syncope in association with the first dose or first few days of therapy. A similar effect can be anticipated if therapy is interrupted for several days and then restarted. Syncope has also been reported with other alpha-adrenergic blocking agents in association with rapid dosage increases or the introduction of another antihypertensive drug. Syncope is believed to be due to an excessive postural hypotensive effect, although occasionally the syncopal episode has been preceded by a bout of severe supraventricular tachycardia with heart rates of 120 to 160 beats per minute. Additionally, the possibility of the contribution of hemodilution to the symptoms of postural hypotension should be considered. To decrease the likelihood of syncope or excessive hypotension, treatment should always be initiated with a 1 mg dose of terazosin capsules, 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 thefirst-dose 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 capsules, 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 capsules 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 otherhave 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 ).

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 (p0.05) 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 SystemTerazosinPlacebo(N = 636)(N = 360)BODY AS A WHOLE * Asthenia7.4% 3.3%Flu Syndrome2.4%1.7%Headache4.9%5.8% CARDIOVASCULAR SYSTEM Hypotension0.6%0.6%Palpitations0.9%1.1%Postural Hypotension3.9% 0.8%Syncope0.6%0.0% DIGESTIVE SYSTEM Nausea1.7%1.1% METABOLIC ANDNUTRITIONAL DISORDERS Peripheral Edema0.9%0.3%Weight Gain0.5%0.0% NERVOUS SYSTEM Dizziness9.1% 4.2%Somnolence3.6% 1.9%Vertigo1.4%0.3% RESPIRATORY SYSTEM Dyspnea1.7%0.8%Nasal Congestion/Rhinitis1.9% 0.0% SPECIAL SENSES Blurred Vision/ Amblyopia1.3%0.6% UROGENITAL SYSTEM Impotence1.6% 0.6%Urinary Tract Infection1.3%3.9% * Includes weakness, tiredness, lassitude, and fatigue. p0.05 comparison between groups. 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 SystemTerazosinPlacebo(N = 636)(N = 360)BODY AS A WHOLE Fever0.5%0.0%Headache1.1%0.8% CARDIOVASCULAR SYSTEM Postural Hypotension0.5%0.0%Syncope0.5%0.0% DIGESTIVE SYSTEM Nausea0.5%0.3% NERVOUS SYSTEM Dizziness2.0%1.1%Vertigo0.5%0.0% RESPIRATORY SYSTEM Dyspnea0.5%0.3% SPECIAL SENSES Blurred Vision/Amblyopia0.6%0.0% UROGENITAL SYSTEM Urinary Tract Infection0.5%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 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. TABLE 3. Adverse Reactions During Placebo-Controlled Trials Hypertension Body SystemTerazosinPlacebo(N = 859)(N = 506)BODY AS A WHOLE * Asthenia11.3% 4.3%Back Pain2.4%1.2%Headache16.2%15.8% CARDIOVASCULAR SYSTEM Palpitations4.3% 1.2%Postural Hypotension1.3%0.4%Tachycardia1.9%1.2% DIGESTIVE SYSTEM Nausea4.4% 1.4% METABOLIC ANDNUTRITIONAL DISORDERS Edema0.9%0.6%Peripheral Adema5.5% 2.4%Weight Gain0.5%0.2% MUSCULOSKETAL SYSTEM PainExtremities3.5%3.0% NERVOUS SYSTEM Depression0.3%0.2%Dizziness19.3% 7.5%Libido Decreased0.6%0.2%Nervousness2.3%1.8%Paresthesia2.9%1.4%Somnolence5.4% 2.6% RESPIRATORY SYSTEM Dyspnea3.1%2.4%Nasal Congestion5.9% 3.4%Sinusitis2.6%1.4% SPECIAL SENSES Blurred Vision1.6% 0.0% UROGENITAL SYSTEM Impotence1.2%1.4% * Includes weakness, tiredness, lassitude, and fatigue. Statistically significant at p=0.05 level. 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 studies 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. TABLE 4. Discontinuation During Placebo-Controlled Trials Hypertension Body SystemTerazosinPlacebo(N = 859)(N = 506)BODY AS A WHOLE Asthenia1.6%0.0%Headache1.3%1.0% CARDIOVASCULAR SYSTEM Palpitations1.4%0.2%Postural Hypotension0.5%0.0%Syncope0.5%0.2%Tachycardia0.6%0.0% DIGESTIVE SYSTEM Nausea0.8%0.0% METABOLIC AND NUTRITIONALDISORDERS Peripheral Edema0.6%0.0% NERVOUS SYSTEM Dizziness3.1%0.4%Paresthesia0.8%0.2%Sonmolence0.6%0.2% RESPIRATORY SYSTEM Dyspnea0.9%0.6%Nasal Congestion0.6%0.0% SPECIAL SENSES Blurred Vision0.6%0.0% 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 PRECAUTIONS ).