HYTRIN®
(terazosin hydrochloride)
CAPSULES
DESCRIPTION
CLINICAL PHARMACOLOGY
INDICATIONS AND USAGE
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
OVERDOSAGE
DOSAGE AND ADMINISTRATION
HOW SUPPLIED
HYTRIN (terazosin hydrochloride), an alpha-1-selective
adrenoceptor blocking agent, is a quinazoline derivative represented by the following chemical
name and structural formula:
(RS)-Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-
4-[(tetra-hydro-2-furanyl)carbonyl]-, monohydrochloride
dihydrate.
Terazosin hydrochloride is a white, crystalline substance,
freely soluble in water and isotonic saline and has a molecular
weight of 459.93. HYTRIN capsules (terazosin hydrochloride
capsules) for oral ingestion are supplied in four dosage
strengths containing terazosin hydrochloride equivalent to
1 mg, 2 mg, 5 mg, or 10 mg of terazosin.
Inactive Ingredients:
1 mg capsules: gelatin, glycerin, iron oxide, methylparaben,
mineral oil, polyethylene glycol, povidone, propylparaben,
titamum dioxide, and vanillin.
2 mg capsules: D&C; yellow No. 10, gelatin, glycerin,
methylparaben, mineral oil, polyethylene glycol, povidone,
propylparaben, titanium dioxide, and vanillin.
5 mg capsules: D&C; red No. 28, FD&C; red No. 40, gelatin,
glycerin methylparaben, mineral oil, polyethylene glycol,
povidone, propylparaben, titanium dioxide, and vanillin.
10 mg capsules: FD&C; blue No. 1, gelatin, glycerin,
methylparaben, mineral oil, polyethylene glycol, povidone,
propylparaben, titanium dioxide, and vanillin.
Pharmacodynamics:
A. Benign Prostatic Hyperplasia (BPH):
The symptoms associated with BPH are related to bladder
outlet obstruction, which is comprised of two underlying
components: a static component and a dynamic component.
The static component is a consequence of an increase in prostate size. Over time, the prostate
will continue to enlarge. However, clinical studies have demonstated that the size of the prostate
does not correlate with the severity of BPH symptoms or the degree of urinary obstruction. The
dynamic component is a function of an icrease in smooth muscle tone in
the prostate and bladder neck, leading to constriction of the
bladder outlet. Smooth muscle tone is mediated by sympathetic nervous stimulation of alpha-1
adrenoceptors, which are
abundant in the prostate, prostatic capsule and bladder neck.
The reduction in symptoms and improvement in urine flow
rates following administration of terazosin is related to relaxation of smooth muscle produced 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 0-3, 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:
a Highest dose 10 mg shown.
b 23% of patients on 10 mg,41% of patients on 20 mg.
c 67% of patients on 10 mg.
* Significantly (p < 0.05) more improvement than placebo.
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
rcsponse in both symptoms and peak flow rate compared to
placebo (Figure 1)
t for baseline values see above table
* p < 0.05, compared to placebo group
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):
* p < 0.05 vs. baseline
mean baseline = 10.7
* p < 0.05 vs. baseline
mean baseline = 9.9
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:
* p < 0.05 vs. placebo
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 dally (the great majority) and twice daily regimens with
total doses usually in the range of 5-20 mg/day and had mild
(about 77%, diastolic pressure 95-105 mmHg or moderate
(23%, diastolic pressure 105-115 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 5-10 mmHg systolic and 3.5 – 8 mmHg diastolic
greater than placebo. The responses in the standing position
tended to be somewhat larger, by 1-3 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 (2-3 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 5-20 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 pressurerelated 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 6-10 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 HYTRIN 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
14.0 and 11.4 hours for the age group > 70 years and the age
group of 20-39 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 20-39
years of age.
The drug is 90-94% 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.
HYTRIN (terazosin hydrochloride) is 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 HYTRIN. The longterm effects of HYTRIN on the incidence
of surgery, acute
urinary obstruction or other complications of BPH are yet to
be determined.
HYTRIN is also indicated for the treatment of hypertension. It can be used alone or in
combination with other antihypertensive agents such as diuretics or beta-adrenergic
blocking agents.
HYTRIN capsules are contraindicated in patients known to be
hypersensitive to terazosin hydrochloride.
Syncope and “First-dose” Effect:
HYTRIN 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 120-160 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, 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.
General:
Prostatic Cancer
Carcinoma of the prostate and BPH cause many of the same
symptoms. These two diseases frequently co-exist. Therefore,
patients thought to have BPH should be examined prior to
starting HYTRIN therapy to rule out the presence of carcinoma of the prostate.
Orthostatic Hypotension
While syncope is the most severe orthostatic effect of terazosin (see Warnings), other symptoms
of lowered blood pres-
sure, such as dizziness, lightheadedness and palpitations,
were more common and occurred in some 28% of patients in
clinical trials of hypertension. In BPH clinical trials, 21% of
the patients experienced one or more of the following: dizziness, hypotension, postural
hypotension, syncope, and vertigo. Patients with occupations in which such events represent
potential problems should be treated with particular caution.
Information for Patients (see Patient Package Insert):
Patients should be made aware of the possibility of syncopal
and orthostatic symptoms, especially at the initiation of therapy, and to avoid driving or
hazardous tasks for 12 hours after
the first dose, after a dosage increase and after interruption of
therapy when treatment is resumed. They should be cautioned
to avoid situations where injury could result should syncope
occur during initiation of terazosin therapy. They should also
be advised of the need to sit or lie down when symptoms of
lowered blood pressure occur, although these symptoms are
not always orthostatic, and to be careful when rising from a
sitting or lying position. If dizziness, lightheadedness, or palpitations are bothersome they should
be reported to the physician, so that dose adjustment can be considered.
Patients should also be told that drowsiness or somnolence
can occur with terazosin, requiring caution in people who
must drive or operate heavy machinery.
Laboratory Tests:
Small but statistically significant decreases in hematocrit,
hemoglobin, white blood cells, total protein and albumin were
observed in controlled clinical trials. These laboratory findings suggested the possibility of
hemodilution. Treatment
with terazosin for up to 24 months had no significant effect on
prostate specific antigen (PSA) levels.
Drug Interactions:
In controlled trials, terazosin has 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: 1)
analgesic/anti-inflammatory(e.g., acetaminophen, aspirin, codeine, ibuprofen, insomethacin); 2) antibiotics
(e.g., erythromycin, trimethoprim and sulfamethoxazole); 3) anticholinergic/sympathomimetics
(e.g., phenylephrine hydrochloride phenylpropanolamine
hydrochloride, psuedoephedrine hydrochloride); 4) antigout
(e.g., allopurinol); 5) antihistamines (e.g., chlorpheniramine);
6 ) cardiovascular agents (e.g., atenolol hydrochlorothiazide,
methylclothiazide, propranolol); 7) corticosteroids; 8) gastrointestinal agents (e.g., antacids); 9) hypoglycemics; 10)
sedatives and tranquilizers (e.g., diazepam).
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:
Terazosin 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).
Terazosin, 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. Terazosin 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 terazosin 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 terazosin 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 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 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. Terazosin 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 adequete 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.
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 is administered to a nursing woman.
Pediatric Use:
Safety and effectiveness in children have not been determined.
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.
t Includes weakness, tiredness, lassitude and fatigue.
* p < 0.05 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.
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.
tIncludes 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 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;
Respiratoty 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.
Post-marketing experience indicates that in rare instances
patients may develop allergic reactions, including anaphylaxis, following administration of
terazosin hydrochloride.
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.
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 terazosin is 90-94%
protein bound; therefore, dialysis may not be of benefit.
If HYTRIN 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 4-6 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 HYTRIN is administered
concomitantly with other antihypertensive agents, especially
the calcium channel blocker verapamil, to avoid the possibility of developing significant
hypotension. When using
HYTRIN and other antihypertensive agents concomitantly,
dosage reduction and retitration of either agent may be necessary (see Precautions).
Hypertension:
The dose of HYTRIN 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 minimalize 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 2-3
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)
HYTRIN capsules (terazosin hydrochloride capsules) are
available in four dosage strengths:
1 mg grey capsules (imprinted with 
and the Abbo-Code HH):
Bottles of 100…………………..(NDC 0074-3805-13),
Abbo-Pac® unit dose strip packages
of 100 capsules………………….(NDC 0074-3805-11).
2 mg yellow capsules (imprinted with and the Abbo-Code HY):
Bottles of 100…………………..(NDC 0074-3806-13),
Abbo-Pac® unit dose strip packages
of 100 capsules …………………(NDC 0074-3806-11).
5 mg red capsules (imprinted with and the Abbo-Code HK):
Bottles of 100…………………..(NDC 0074-3807-13),
Abbo-Pac® unit dose strip packages
of 100 capsules………………….(NDC 0074-3807-11).
10 mg blue capsules (imprinted with and the Abbo-Code HN):
Bottles of 100…………………..(NDC 0074-3808-13),
Abbo-Pac® unit dose strip packages
of 100 capsules………………….(NDC 0074-3808-11).
Recommended storage: Store at controlled room temperature
between 20-25蚓 (68-77蚌). See USP. Protect from light and
moisture.
Revised: October, 1994
