Approval Date: 01/01/2007
Revision Date: 07/16/2010
December 30, 2011
November 01, 2012
December 01, 2013
October 18, 2015
December 23, 2018
Terazosin Hydrochloride Tablets Instructions
Please read the instruction manual carefully and use under the guidance of your physician
[Drug Name].
Generic Name: Terazosin Hydrochloride Tablets
Trade name: Marsanib®
English Name: Terazosin Hydrochloride Tablets
Hanyu Pinyin: Yansuan Telazuoqin Pian
[Ingredients
The main ingredient of this product: Terazosin Hydrochloride
Chemical name: 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(tetrahydro-2-furanylcarbonyl)piperazine hydrochloride dihydrate.
Chemical structure formula.
Molecular Formula: C19H25N5O4-HCl-2H2O
Molecular weight: 459.93
[Properties
This product is a white or off-white tablet.
[Indications
Oral administration of this product is indicated for the treatment of mild or moderate hypertension and can be used in combination with thiazide diuretics or other antihypertensive drugs, as well as alone when other drugs are not indicated or are ineffective. This product primarily lowers diastolic blood pressure.
Oral administration of this product is also indicated for the treatment of symptoms caused by benign prostatic hyperplasia (BPH).
[Specifications
2mg (based on C19H25N5O4)
[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. After one week, the single daily dose may be doubled to achieve the desired effect. The usual maintenance dose is 2 to 10 mg once daily. no increase in efficacy has been seen with doses above 20 mg, and no studies have been conducted with doses above 40 mg.
Benign prostatic hyperplasia (BPH).
Adjust the dose administered according to the patient’s response. 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 daily dose may be doubled after one or two weeks to achieve the desired effect. The usual maintenance dose is 5 to 10 mg once daily, with significant improvement in symptoms after two weeks of dosing. To date, there are insufficient data to suggest that doses above 10 mg once daily cause further symptomatic relief.
Treatment should be initiated with the initial dose and summarized after four weeks. Temporary adverse reactions may occur with each dose adjustment. If adverse reactions persist, a reduction in the dose administered should be considered.
[Adverse Reactions].
The most common are: weakness, palpitations, nausea, peripheral edema, dizziness, drowsiness, nasal congestion/rhinitis, and blurred/amblyopic vision.
In addition, the following adverse effects have been reported: back pain, headache, tachycardia, postural hypotension, syncope, edema, weight gain, extremity pain, decreased libido, depression, neuroticism, sensory abnormalities, dyspnea, sinusitis, and impotence.
Other adverse reactions reported in clinical trials and less clearly related to the use of this product in market feedback reports: chest pain, facial edema, fever, abdominal pain, neck pain, shoulder pain, vasodilation, arrhythmia, constipation, diarrhea, dry mouth, dyspepsia, gastrointestinal gas, vomiting, gout, arthralgia, arthritis, joint disorders, myalgia, anxiety, insomnia, bronchitis rhinorrhea, flu symptoms, pharyngitis, rhinitis, cold symptoms, itching, rash, cough, sweating, visual abnormalities, conjunctivitis, tinnitus, frequent urination, urinary tract infections, and early urinary incontinence in postmenopausal women.
At least two cases of allergic reactions have been reported with this product.
Thrombocytopenia and abnormal penile erection have been reported with this product, and atrial fibrillation has also been reported, but a causal relationship has not been established.
Laboratory tests: Small but statistically significant reductions in hematocrit, hemoglobin, white blood cells, total protein, and albumin were found in controlled clinical trials. These laboratory results suggest the possibility of plasma dilution. Continuous treatment with this product for more than 24 months had no significant effect on prostate-specific antigen (PSA) levels.
Postmarketing Experience: A variant form of alpha-1 blocker-related micropupillary syndrome, intraoperative iris relaxation syndrome (IFIS), has been reported during cataract surgery.
[Contraindicated].
It is contraindicated in persons with known sensitivity to alpha-adrenoceptor antagonists.
[Precautions].
No change in recommended dose is required in patients with renal impairment.
The dosage of terazosin should be reduced when adding a thiazide diuretic or other antihypertensive agent, and the dosage should be readjusted if necessary. Care should be taken to prevent hypotension when terazosin is combined with thiazide diuretics or other antihypertensives.
As with other α-adrenergic receptor antagonists, terazosin is not recommended for patients with a history of voiding syncope.
Upright hypotension occurs more frequently in patients with BPH than in those with hypertension, with older patients being more prone to it than younger patients.
If dosing is interrupted for several days, treatment should be resumed with the initial dosing regimen.
Dizziness, mild headache, or drowsiness may occur with initial dosing or discontinuation, or with re-dosing after discontinuation; avoidance of driving or hazardous work for 12 hours after the initial dose is given or when the dose is increased is recommended.
Like other alpha-adrenergic receptor antagonists, terazosin can cause vertigo. Vertigo often occurs within 30 to 90 minutes of initial dosing and occasionally when the dose is increased too rapidly or when another antihypertensive drug is added. If vertigo occurs, the patient should be placed in a transverse position and supportive therapy should be used if necessary. Although tachycardia (heart rate of 120 to 160 beats per minute) occasionally occurs before syncope, syncope is usually thought to be associated with excessive upright hypotension.
Dizziness, mild headache, and even syncope may occur when there is a sudden shift from a recumbent or seated position to an upright position. When these symptoms occur, the patient should lie down and then sit for a few moments before standing to prevent recurrence of symptoms. In most cases, this reaction does not recur after the initial or continuous phase of treatment.
Prostate cancer shares many of the same symptoms as BPH, and the two may often occur together, so the possibility of prostate cancer should be ruled out before using this product for BPH.
Treatment with this and other similar drugs may cause hetero-erection, which is rare but can lead to permanent impotence if left untreated.
Cataract surgery: Intraoperative iris relaxation syndrome (IFIS) has been observed in some patients undergoing or previously treated with alpha-1 blockers during cataract surgery. It is characterized by a loosening of the iris and a violent surge in response to irritating irrigation during surgery; a persistent narrowing during surgery, even when dilated with standard preoperative dilators; and a possible prolapse of the iris from the lens emulsion incision. The ophthalmologist should be prepared to make technical corrections to the surgical technique, such as the use of iris traction hooks, iris dilation, or viscoelastic, when performing this procedure. Discontinuation of alpha-1 blocking therapy before cataract surgery has not been shown to be beneficial.
[Use in 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
Unclear.
[Geriatric use].
Pharmacokinetic studies suggest that the recommended dose does not need to be changed when using this product in the elderly. Upright hypotension is more likely to occur in older patients than in younger patients when using terazosin for BPH.
[Drug Interactions].
A higher proportion of patients treated with this product in combination with angiotensin (ACE) inhibitors or diuretics reported vertigo or other related adverse reactions in foreign clinical trials than in all patients treated with this product. Care should be taken when combining this product with other antihypertensive drugs to avoid significant hypotension. When this product is added to a diuretic or other antihypertensive drug, the dose should be reduced and, if necessary, reformulated.
This product is not known to interact with analgesics/anti-inflammatory drugs, cardiac glycosides, hypoglycemic agents, antiarrhythmic drugs, anxiolytics/sedatives, antibacterial agents, hormones/steroids, and drugs for gout.
There have been reports of hypotension in combination with phosphodiesterase (PDE-5) inhibitors.
[Drug overdose
Overdose may result in acute hypotension, in which case cardiovascular support therapy should be used. The patient should lie supine to allow blood pressure to return and heart rate to normalize. If this approach does not resolve the problem, then volume expansion should be used first to treat shock and, if necessary, vasopressors. Renal function should be monitored and conventional supportive therapy applied. Dialysis is ineffective because of the high plasma protein binding rate of this product.
[Pharmacology and Toxicology
Pharmacological effects
While the exact mechanism of the hypotensive effect of terazosin hydrochloride has not been established to date, the relaxation of peripheral vasculature is primarily due to competitive antagonism of postsynaptic α-adrenergic receptors. Terazosin produces a slow blood pressure-lowering effect at the beginning and then exerts a sustained antihypertensive effect.
Clinical experience suggests that a 2-5% reduction in total plasma cholesterol and a 3-7% reduction in the LDLc+VLDLc binding fraction are associated with terazosin treatment doses.
Mild reductions in total cholesterol and plasma concentrations of bound LDL and VLDLc were observed in clinical trials with terazosin hydrochloride. No increase in total cholesterol was seen with the combination of other antihypertensive agents that elevate total plasma cholesterol.
Studies have shown that antagonism of α1-adrenoceptors is beneficial in improving urethral function in patients with chronic bladder block (e.g., benign prostatic hyperplasia, BPH), whose symptoms are mainly caused by prostatic hyperplasia and increased urethral outlet and prostatic smooth muscle thresholds (mainly due to α11). (primarily regulated by alpha1adrenergic receptors).
In vitro tests have shown that terazosin hydrochloride antagonizes phenylephrine-induced contraction of human prostate tissue. Terazosin hydrochloride has also been shown in clinical trials to improve urethral function and symptoms in patients with BPH.
Toxicity studies
Genotoxicity.
Terazosin hydrochloride was not potentially mutagenic in in vivo and ex vivo assays (Ames test, cytogenetic in vivo assay, mouse dominant lethal assay, Chinese hamster chromosomal aberration in vivo assay, and V79 cell forward mutation assay).
Reproductive toxicity.
Rats were given 8, 30 and 120 mg/kg of terazosin by daily gavage to study fertility/reproductive effects. The results showed that 4 of 20 male rats in the 30 mg/kg group (240 mg/M2, 20 times the maximum recommended human dose) and 5 of 19 male rats in the 120 mg/kg group (960 mg/M2, 80 times the maximum recommended human dose) lost fertility. Testicular weight and shape were not affected. Post-mating vaginal smears showed a lower sperm count in the 30 and 120 mg/kg groups compared to the control group, and sperm count correlated well with the number of pregnant litters.
Testicular atrophy was significantly increased in rats given orally 40 and 250 mg/kg daily (29 and 175 times the maximum recommended human dose) for 1 or 2 years, but was not seen at 8 mg/kg daily (greater than 6 times the maximum recommended human dose). Testicular atrophy was also seen in dogs given terazosin 300 mg/kg daily for 3 months (500 times the maximum recommended human dose). However, no testicular atrophy was observed with daily administration of 20 mg/kg of terazosin (38 times the maximum recommended human dose) for 1 year. Prazosin (a selective α1 receptor blocker) can also cause this injury.
Terazosin was not teratogenic in rats and rabbits given daily orally at 280 and 60 times the maximum recommended human dose, respectively. Absorption of fetuses was seen in rats given 480 mg/kg daily (280 times the maximum recommended human dose). Increased fetal absorption, reduced fetal weight and multiple fetuses in the offspring were seen in rabbits given 60 times the maximum recommended human dose of terazosin daily. This phenomenon may be a secondary response to maternal toxicity.
The number of pup deaths was significantly increased in the rat group given 120 mg/kg daily (>75 times the maximum recommended human dose) of terazosin compared to the control group.
Carcinogenic effects
Prolonged administration of high doses of terazosin to male rats caused tumorigenesis, but this phenomenon was not seen in female rats and mice. The relevance of this phenomenon to human clinical dosing is not known.
[Pharmacokinetics
Prodrug plasma concentration maxima occur about 1 hour after dosing, with a half-life of approximately 12 hours. Food rarely, if ever, affects terazosin bioavailability. Approximately 40% of the administered amount is excreted in the urine and 60% in the feces. Terazosin has a high plasma protein binding rate.
[Storage]Store under shade and seal.
[Packaging
Aluminium-plastic packaging: 14 tablets/plate, 1 plate/box.
Aluminium-plastic packaging: 14 tablets/plate, 2 plates/box.
Aluminium-plastic packaging: 20 tablets/plate, 1 plate/box.
[Expiration date]24 months
[Executive Standard].
[Approval number]State Drug Administration H10970081
[Manufacturer
Company Name: China Resources Saike Pharmaceutical Co.
Manufacturing Address: No. 3 Jinghai 7 Road, Zhongguancun Science and Technology Park, Tongzhou District, Beijing
Postal Code: 101111
Phone number: 400-810-8780
Fax Number: 010-67793887
Web Address: www.saike.com.cn