Terazosin 5 MG Oral Capsule
WARNINGS
Syncope and “First-dose” Effect 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 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 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 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 ).
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).
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.
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 19H 26ClN 5O 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.
HOW SUPPLIED
Terazosin Capsules are available in four dosage strengths: 1 mg Terazosin Capsules, USP are available as gray opaque cap/body printed “TL 383” in black ink.
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 ivory opaque cap/body printed “TL 384” in black ink.
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 bright orange opaque cap/body printed “TL 385” in black ink.
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 light green opaque cap/body printed “TL 386” in black ink.
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° – 25°C (68° – 77°F) [see USP Controlled Room Temperature].
Protect from light and moisture.
Rx only Revised 08/12 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.
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.
PEDIATRIC USE
Pediatric Use : Safety and effectiveness in pediatric patients have not been determined.
PREGNANCY
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.
NUSRING MOTHERS
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.
INFORMATION FOR PATIENTS
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.
Patients should be advised about the possibility of priapism as a result of treatment with terazosin capsules and other similar medications.
Patients should know that this reaction to terazosin capsules is extremely rare, but that if it is not brought to immediate medical attention, it can lead to permanent erectile dysfunction (impotence).
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 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.)