Label: TERAZOSIN HYDROCHLORIDE capsule

Terazosin hydrochloride, an alpha-1-selective adrenoceptor blocking agent, is 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. C19H26ClN5O4

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.

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 demonstrated 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 increase 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 extensively 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:

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 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):

Terazosin hydrochloride 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 hydrochloride. The long term effects of terazosin on the incidence of surgery, acute urinary obstruction or other complications of BPH are yet to be determined.

Terazosin hydrochloride capsule 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.

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

Syncope and “First-dose” Effect

Terazosin hydrochloride 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 about of severe supraventricular tachycardia with heart rates of120-160 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 witha1 mg dose of terazosin, given at bedtime. The 2mg, 5mg 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 α1-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).

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.

 

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 anaphlaxis, 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).

Should overdosage of terazosin hydrochloride 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 the administration of terazosin hydrochloride capsule 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, or10 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 4-6weeksmay 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 20mg 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 hydrochloride is administered concomitantly with other antihypertensive agents, especially the calcium channel blocker verapamil, to avoid the possibility of developing significant hypotension. When using terazosin hydrochloride and other antihypertensive agents concomitantly, dosage reduction and retitration of either agent may be necessary (see Precautions).

Hypotension has been reported when terazosin hydrochloride has been used with phosphodiesterase-5 (PDE-5) inhibitors.

Hypertension:

The dose of terazosin hydrochloride 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 2-3 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).

5 mg Terazosin Hydrochloride Capsules (equivalent to 5 mg terazosin) are available as bright orange opaque cap/body printed "TL 385" in black ink.

Available in:

Bottles of 30:      NDC 42549-666-30


Dispense in a tight, light-resistant container as defined in the USP


Recommended storage:  Store at 20 - 25 degrees C (68 - 77 degrees F) [see USP Controlled Room Temperature].  Protect from light and moisture.


Revised 04/11

Julilant 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.


Relabeling and Repackaging by:
STAT Rx USA LLC
Gainesville, GA  30501

PATIENT INFORMATION ABOUT
TERAZOSIN HYDROCHLORIDE
CAPSULES
Generic Name: Terazosin
(Ter-A-so-sin) Hydrochloride

When used to treat Hypertension or Benign Prostatic Hyperplasia (BPH)

Please read this leaflet before you start taking TERAZOSIN HYDROCHLORIDE CAPSULES. Also, read it each time you get a new prescription. This is a summary and should NOT take the place of a full discussion with your doctor who has additional information about TERAZOSIN HYDROCHLORIDE CAPSULES. You and your doctor should discuss TERAZOSIN HYDROCHLORIDE CAPSULES and your condition before you start taking it and at your regular check-ups.

TERAZOSIN HYDROCHLORIDE CAPSULES are used to treat high blood pressure (hypertension). TERAZOSIN HYDROCHLORIDE CAPSULES are also used to treat benign prostatic hyperplasia (BPH) in men. This leaflet describes TERAZOSIN HYDROCHLORIDE CAPSULES as a treatment for hypertension or BPH.

What is hypertension (high blood pressure)?

Blood pressure is the tension of the blood within the blood vessels. If blood is pumped too forcefully, or if the blood vessels are too narrow, the pressure of the blood against the walls of the vessels rises. If high blood pressure is not treated, over time, the increased pressure can damage blood vessels or it can cause the heart to work too hard and may decrease the flow of blood to the heart, brain, and kidneys. As a result, these organs may become damaged and not function correctly. If high blood pressure is controlled, this damage is less likely to happen.

Treatment options for hypertension

Non-drug treatments are sometimes effective in controlling mild hypertension. The most important lifestyle changes to lower blood pressure are to lose weight, reduce salt, fat, and alcohol in the diet, quit smoking, and exercise regularly. However, many hypertensive patients require one or more ongoing medications to control their blood pressure. There are different kinds of medications used to treat hypertension. Your doctor has prescribed TERAZOSIN HYDROCHLORIDE CAPSULES for you.

What TERAZOSIN HYDROCHLORIDE CAPSULES do to treat hypertension

TERAZOSIN HYDROCHLORIDE CAPSULES work by relaxing blood vessels so that blood passes through them more easily. This helps to lower blood pressure.

What is BPH?

The prostate is a gland located below the bladder of men. It surrounds the urethra (you-REETH-rah), which is a tube that drains urine from the bladder. BPH is an enlargement of the prostate gland. The symptoms of BPH, however, can be caused by an increase in the tightness of muscles in the prostate. If the muscles inside the prostate tighten, they can squeeze the urethra and slow the flow of urine. This can lead to symptoms such as:

• a weak or interrupted stream when urinating
• a feeling that you can not empty your bladder completely
• a feeling of delay when you start to urinate
• a need to urinate often, especially at night, or
• a feeling that you must urinate right away

 

Treatment options for BPH

There are three main treatment options for BPH:

• Program of monitoring or "Watchful Waiting".

Some men have an enlarged prostate gland, but no symptoms, or symptoms that are not bothersome. If this applies, you and your doctor may decide on a program of monitoring including regular checkups, instead of medication or surgery.

• Medication. There are different kinds of medication used to treat BPH. Your doctor has prescribed TERAZOSIN HYDROCHLORIDE CAPSULES for you. See "What TERAZOSIN HYDROCHLORIDE CAPSULES do to treat BPH" below.
• Surgery. Some patients may need surgery.

Your doctor can describe several different surgical procedures to treat BPH. Which procedure is best depends on your symptoms and medical condition.

What TERAZOSIN HYDROCHLORIDE CAPSULES do to treat BPH

TERAZOSIN HYDROCHLORIDE CAPSULES relax the tightness of a certain type of muscle in the prostate and at the opening of the bladder. This may increase the rate of urine flow and/or decrease the symptoms you are having.

• TERAZOSIN HYDROCHLORIDE CAPSULES help relieve the symptoms of BPH. It does NOT change the size of the prostate, which may continue to grow. However, a larger prostate does not necessarily cause more or worse symptoms.

• If TERAZOSIN HYDROCHLORIDE CAPSULES are helping you, you should notice an effect on your particular symptoms in 2 to 4 weeks of starting to take the medication.

• Even though you take TERAZOSIN HYDROCHLORIDE CAPSULES and they may help you, TERAZOSIN HYDROCHLORIDE CAPSULES may not prevent the need for surgery in the future.

 

Other important facts about TERAZOSIN HYDROCHLORIDE CAPSULES for BPH

• You should see an effect on your symptoms in 2 to 4 week. So, you will need to continue seeing your doctor to check your progress regarding your BPH and to monitor your blood pressure in addition to your other regular check-ups.

• Your doctor has prescribed TERAZOSIN HYDROCHLORIDE CAPSULES for your BPH and not for prostate cancer. However, a man can have BPH and prostate cancer at the same time. Doctors usually recommend that men be checked for prostate cancer once a year when they turn 50 (or 40 if a family member has had prostate cancer). These checks should continue even if you are taking TERAZOSIN HYDROCHLORIDE CAPSULES. TERAZOSIN HYDROCHLORIDE CAPSULES are not a treatment for prostate cancer.

• About Prostate Specific Antigen (PSA). Your doctor may have done a blood test called PSA. Your doctor is aware that TERAZOSIN HYDROCHLORIDE CAPSULES do not affect PSA levels. You may want to ask your doctor more about this if you have had a PSA test done.

 

What you should know while taking TERAZOSIN HYDROCHLORIDE CAPSULES for hypertension or BPH

WARNINGS

TERAZOSIN HYDROCHLORIDE CAPSULES Can Cause A Sudden Drop In Blood Pressure After the VERY FIRST DOSE. You may feel dizzy, faint, or "lightheaded" particularly after you get up from bed or from a chair. This is more likely to occur after you've taken the first few doses, but can occur at any time while you are taking the drug. It can also occur if you stop taking the drug and then re-start treatment.

Because of this effect, your doctor may have told you to take TERAZOSIN HYDROCHLORIDE CAPSULES at bedtime. If you take TERAZOSIN HYDROCHLORIDE CAPSULES at bedtime but need to get up from bed to go to the bathroom, get up slowly and cautiously until you are sure how the medicine affects you. It is also important to get up slowly from a chair or bed at any time until you learn how you react to TERAZOSIN HYDROCHLORIDE CAPSULES. You should not drive or do any hazardous tasks until you are used to the effects of the medication. If you begin to feel dizzy, sit or lie down until you feel better.

• You will start with a 1 mg dose of TERAZOSIN HYDROCHLORIDE CAPSULES. Then the dose will be increased as your body gets used to the effect of the medication.

• Other side effects you could have while taking TERAZOSIN HYDROCHLORIDE CAPSULES include drowsiness, blurred or hazy vision, nausea or "puffiness" of the feet or hands. Discuss any unexpected effects you notice with your doctor. Extremely rarely, TERAZOSIN HYDROCHLORIDE CAPSULES and similar medications have caused painful erection of the penis sustained for hours and unrelieved by sexual intercourse or masturbation. This condition is serious, and if untreated it can be followed by permanent inability to have an erection. If you have a prolonged abnormal erection, call your doctor or go to an emergency room as soon as possible.

 

How to take TERAZOSIN HYDROCHLORIDE CAPSULES

Follow your doctor's instructions about how to take TERAZOSIN HYDROCHLORIDE CAPSULES. You must take it every day at the dose prescribed. Talk with your doctor if you don't take it for a few days, you may have to restart it at a 1 mg dose and be cautious about possible dizziness. Do not share TERAZOSIN HYDROCHLORIDE CAPSULES with anyone else; it was prescribed only for you.

Keep TERAZOSIN HYDROCHLORIDE CAPSULES and all medicines out of the reach of children.

Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.

FOR MORE INFORMATION ABOUT TERAZOSIN HYDROCHLORIDE CAPSULES AND HYPERTENSION OR BPH, TALK WITH YOUR DOCTOR, NURSE, PHARMACIST OR OTHER HEALTH CARE PROVIDER.

Revised 04/11

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.

Relabeling and Repackaging by:
STAT Rx USA LLC
Gainesville, GA  30501