Approval date: March 07, 2007
Revision date: December 30, 2011
Revision date: December 01, 2013
Revision date: December 01, 2015
Revision date: December 13, 2018
Terazosin Hydrochloride Capsules Instructions
Please read the instructions carefully and use under the guidance of your physician
[Drug Name].
Generic Name: Terazosin Hydrochloride Capsules
Trade Name: Tylenol
English Name: Terazosin Hydrochloride Capsules
Hanyu Pinyin: Yansuan Telazuoqin Jiaonang
[Ingredient
The main ingredient of this product is terazosin hydrochloride.
Chemical name: 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(tetrahydro-2-furancarbonyl)piperazine hydrochloride dihydrate.
Chemical structure formula.
Molecular formula: C19H25N5O4-HCl-2H2O
Molecular weight: 459.93
[Properties
The content of this product is white or off-white granules or powder.
[Indications
1. For the treatment of hypertension, it can be used alone or together with other anti-hypertensive drugs.
2. Used to improve urinary symptoms in patients with BPH, such as: urinary frequency, urinary urgency, thinning of the urinary line, difficulty in urination, increased nocturia, and a feeling of incomplete urination.
[Specifications
According to C19H25N5O4 (1) 1mg (2) 2mg
[Dosage].
Hypertension.
The initial dose is 1 mg at bedtime and should not be exceeded to minimize the occurrence of hypotensive events with the first dose. The dose is gradually increased until satisfactory efficacy occurs. The commonly used maintenance dose is 1 to 5 mg daily, with a maximum daily dose of 20 mg daily. no increase in efficacy has been seen with doses above 20 mg, and no studies have been conducted with doses above 40 mg. If discontinued for a few days or longer, treatment should be restarted using the initial dosing regimen.
Benign prostatic hyperplasia.
The initial dose is 1 mg at bedtime and should not be exceeded to minimize the incidence of hypotensive events with the first dose. The dose should be gradually increased to 2 mg, 5 mg, or 10 mg once daily until satisfactory efficacy occurs. The usual maintenance dose is 10 mg daily. if discontinued for a few days or longer, treatment should be restarted using the initial dosing regimen.
[Adverse Reactions
Benign prostatic hyperplasia
Six placebo-controlled clinical trials of terazosin and placebo in BPH demonstrated that the incidence of adverse events was at least 1% with terazosin 1 to 20 mg once daily and was higher than placebo controls, or clinically significant adverse events; the most common adverse events with terazosin included weakness, postural hypotension hypotension, dizziness, drowsiness, nasal congestion/rhinitis, and impotence, and all other adverse events were more common than in the placebo group (p≤0.05). The incidence of urinary tract infections was significantly lower in the terazosin group (Table 1). The risk of hypotensive adverse events was greatest during the first 7 days of treatment and including each dosing interval.
Table 1: Adverse reactions during a placebo-controlled trial for benign prostatic hyperplasia
Body SystemTerazosin (N=636)Placebo (N=360)Full body *Powerless7.4%†3.3%Influenza Complication Symptoms2.4%1.7% Headache4.9%5.8%Cardiovascular System Low blood pressure0.6%0.6%Heart palpitations0.9%1.1% Postural hypotension3.9%†0.8%swoon0.6%0.0%Digestive system Nauseous1.7%1.1%Metabolic and nutritional disorders Peripheral edema0.9%0.3%weight gain
Adverse reactions that occurred in at least 1% of patients taking the drug in 1987 controlled or open, short-term or long-term clinical trials or that were reported post-marketing were as follows: systemic: chest pain, facial edema, fever, abdominal pain, neck pain, shoulder pain; cardiovascular: arrhythmias, vasodilation; digestive: constipation, diarrhea, dry mouth, dyspepsia, gastrointestinal gas, vomiting The musculoskeletal system: arthralgia, arthritis, arthrosis, myalgia; the nervous system: anxiety, insomnia; the respiratory system: bronchitis, cold symptoms, rhinorrhea, flu symptoms, cough aggravation, pharyngitis, rhinitis; the skin and its adnexa: pruritus, rash, sweating; special sensations: visual abnormalities, conjunctivitis, tinnitus; the genitourinary system: urinary frequency, urinary incontinence (mainly seen in postmenopausal women), urinary tract infection.
Post-marketing experience
Post-market experience has shown that allergic reactions, including systemic hypersensitivity reactions, have been reported rarely. Abnormal penile erection and thrombocytopenia have been reported, and atrial fibrillation has been reported.
The occurrence of various small pupil syndromes, or intraoperative iris relaxation syndrome (IFIS), associated with α-1 receptor blocker therapy during cataract surgery has been reported.
[Contraindicated].
This product is contraindicated in patients with hypersensitivity to terazosin hydrochloride.
[Precautions].
1. Prostate cancer
Prostate cancer and BPH cause many of the same symptoms. The two diseases often coexist. Therefore, it is thought that patients with BPH should be tested to rule out the presence of prostate cancer prior to treatment with terazosin capsules.
Upright hypotension
Although syncope is the most severe upright response to terazosin, other symptoms of hypotension are more common, such as dizziness, mild headache, and palpitations. In clinical trials of hypertension, the symptom was seen in 28% of patients. In the BPH trial, 21% of patients experienced one or more of the following symptoms: dizziness, hypotension, postural hypotension, syncope, and mild headache. The above events are potentially dangerous in certain occupations, and patients in these occupations should be treated with special caution.
Patients should be advised that this product may cause syncope and upright hypotension, especially at the initiation of therapy and to avoid driving or hazardous operations 12 hours after the initial dose, after a dose increase, or when therapy is interrupted and then restarted. Remind patients to avoid injury due to syncope during initiation of terazosin hydrochloride therapy. Patients should be advised to sit or lie down when symptoms of hypotension occur, although these symptoms are not always upright, and caution should be exercised when the patient stands up from a sitting or lying position. If symptoms of dizziness, lightheadedness, or palpitations are uncomfortable, the physician should be informed so that a dose adjustment can be considered.
3. Patients should be informed that drowsiness or somnolence may occur with terazosin treatment and caution should be exercised by those who must drive or operate heavy machinery.
4. Patients should be informed that treatment with terazosin hydrochloride or other similar drugs may result in abnormal penile erections. Patients should be aware that the reaction is relatively rare, but it can lead to permanent erectile dysfunction (impotence) if not brought to the physician’s attention in a timely manner.
5. Laboratory tests
In controlled clinical trials, a slight but statistically significant decrease in hematocrit, hemoglobin, leukocytes, total protein, and albumin levels was observed with terazosin. This suggests that terazosin may have a hemodiluting effect. Treatment with terazosin capsules for up to 24 months did not significantly affect prostate-specific antigen (PSA) levels.
6. iris relaxation syndrome (IFIS)
Intraoperative iris relaxation syndrome (IFIS) has been found to occur during cataract surgery in some patients who are currently or have been treated with alpha-1 receptor blockers. The iris may prolapse from the cataract ultrasound incision. The patient’s ophthalmologist should be prepared for possible modifications to their surgical approach, such as the use of iris hooks, iris dilating rings, or viscoelastic substances. Discontinuation of α-1 receptor blocker therapy before cataract surgery does not appear to be beneficial.
7. Syncope and the “first dose” effect
Terazosin capsules, like other α-adrenergic receptor blockers, may cause a significant decrease in blood pressure, especially postural hypotension; syncope may occur with the first dose or during the first few days of the course, and similar adverse effects may occur when the course is restarted after a few days of interruption. Syncope can also result from rapid dose increases with other alpha-adrenergic receptor blockers or when other antihypertensive agents are added. It is generally accepted that syncope is due to an excessive postural hypotensive response, but episodes of syncope are occasionally preceded by supraventricular tachycardia with a heart rate of 120 to 160 beats per minute. In addition, the exacerbation of postural hypotension symptoms by hemodilution should be considered.
To reduce the likelihood of syncope or excessive hypotension, the initial dose of terazosin capsules should be 1 mg and taken at bedtime. 2 mg capsules are not appropriate as an initial dose. The dose should be increased slowly and other antihypertensive drugs should be added with caution as recommended in the dosage section. Patients should be advised that syncope may occur at the beginning of the course and that driving or performing hazardous operations should be avoided to prevent injury from sudden syncope.
If syncope occurs, the patient should be made to lie flat and given supportive therapy if necessary. There is evidence that the upright position reaction to terazosin capsules is worse when the drug is first taken, even when taken for a long period of time. The incidence of this adverse reaction is most severe during the first seven days of treatment and continues throughout the dosing period.
[For pregnant and lactating women
This product is contraindicated in pregnant women, and lactation should be discontinued in nursing women when using this product.
[For Children].
The safety and efficacy of this product in children have not been established.
[For use in the elderly
This trial was not conducted and no references are available.
[Drug Interactions].
In controlled trials, no unintended interactions have been observed with terazosin capsules in combination with diuretics and certain beta-adrenergic blockers. Terazosin has been co-administered with the following classes of drugs.
1. analgesic/anti-inflammatory drugs (e.g., acetaminophen, aspirin, codeine, ibuprofen, indomethacin).
2. antibiotics (e.g., erythromycin, methotrexate, and sulfamethoxazole).
3. anticholinergic/sympathomimetic drugs (e.g., phenylephrine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride).
4. antigout medications (e.g., allopurinol).
5. antihistamines (e.g. chlorpheniramine).
6. cardiovascular drugs (e.g. atenolol, hydrochlorothiazide, metachlorothiazide, propranolol).
7. corticosteroids.
8. Gastrointestinal drugs (e.g., antacids).
9. hypoglycemic drugs.
10. Sedative and tranquilizing drugs (e.g., diazepam).
In combination with other drugs
When terazosin and verapamil were given together (n=24), the mean AUC 0-24 of terazosin increased by 11% when verapamil was first given and by 24% after 3 weeks of treatment with verapamil, and the mean Cmax and Cmin increased by 25% and 32%, and the mean Tmax of terazosin decreased from 1.3 hours to 0.8 hours at this time. No significant effect was found on verapamil. When terazosin and captopril were administered concomitantly (n=6), plasma concentrations of captopril were not affected by terazosin. When terazosin was combined with captopril to reach steady state, the maximum plasma concentration of terazosin increased linearly with dose.
[Drug overdose].
Overdose can result in hypotension, in which case cardiovascular support therapy should be used. The patient should lie on his or her back to allow blood pressure to return as well as normalize the heart rate. If this approach does not resolve, then volume expansion should be used first to treat shock. Use vasopressors if necessary. Renal function should be monitored and conventional supportive therapy applied. Laboratory data suggest that plasma protein binding of terazosin is 90% to 94%; therefore, dialysis is ineffective.
[Pharmacologic Toxicology].
Pharmacology
Terazosin reduces peripheral vascular resistance and relaxes prostatic smooth muscle by blocking α1-adrenergic receptors.
Toxicological studies
Genotoxicity
Terazosin was not potentially mutagenic in the Ames test, cytogenetic in vivo assay, dominant lethal assay in mice, Chinese hamster chromosome aberration assay, and V79 cell forward mutation assay.
Reproductive toxicity
A reduction in sperm count and loss of fertility was seen in male rats given orally 8, 30 and 120 mg/kg/day of terazosin, and testicular weight and shape were not affected. fertility was not affected in male rats at a dose of 8 mg/kg (>6 times the maximum recommended human dose of 20 mg).
In rats given orally 480 mg/kg/day (280 times the maximum recommended human dose) of terazosin, an increase in fetal uptake was seen. In rabbits given orally 60 times the maximum recommended human dose of terazosin daily, an increase in absorbed fetuses, reduced litter weight, and multiple ribs were seen.
In rats, perinatal oral administration of terazosin at 120 mg/kg/day (greater than 75 times the maximum recommended human dose) resulted in increased pup mortality 3 weeks after delivery.
Carcinogenicity
In rats given terazosin 8, 40, and 250 mg/kg/day (70, 350, and 2100 mg/M2/day) by adulteration for 2 years, the incidence of benign adrenal medullary tumors was increased in male rats in the 250 mg/kg group (175 times the maximum recommended human dose). No effect was seen in female rats. No carcinogenicity was seen in mice given 32 mg/kg/day (110 mg/M2/day, 9 times the maximum recommended human dose) of terazosin by adulteration for 2 consecutive years. The relevance of this phenomenon to human clinical dosing is not known.
[Pharmacokinetics].
Terazosin is largely completely absorbed after oral administration in humans. Postprandial administration of this product has minimal effect on the degree of absorption, but delays the time to peak plasma concentration by approximately 40 minutes. The hepatic first-pass metabolism of terazosin is minimal, and almost all of it is present in the body as a prototype drug. Plasma concentrations peak approximately 1 hour after administration, with a half-life of approximately 12 hours. In a study evaluating the effect of age on the pharmacokinetics of terazosin, plasma half-lives of 14.0 and 11.4 hours were found in patients aged 70 years or older and 20 to 39 years, respectively. The plasma protein binding rate of this product was 90% to 94%. About 40% is excreted in the urine and about 60% is excreted in the feces.
[Storage]Sheltered from light and stored under 30°C in a sealed container.
[Package]Polyvinyl chloride solid pharmaceutical hard tablets and aluminum foil for pharmaceutical packaging, 6 tablets per plate, 2 plates per box; 6 tablets per plate, 8 plates per box.
[Expiration date]24 months
[Executive Standard].
[Approval number] (1)国药准字H20000093 (2)国药准字H20000094
[Manufacturer
Company name: Yangtze River Pharmaceutical Group Jiangsu Pharmaceutical Co.
Production Address: No. 2 Tongjiang East Road, Gaogang District, Taizhou City, Jiangsu Province
Postal Code: 225321
Phone number: 400-988-1999
Fax number: (0523)86976161
Web Address: www.yangzijiang.com