Each tablet contains: Doxazosin mesylate eq. to Doxazosin 1 mg.
Each tablet contains: Doxazosin mesylate eq. to Doxazosin 2 mg.
Each tablet contains: Doxazosin mesylate eq. to Doxazosin 4 mg.
Pharmacology: Doxazosin has a selective postsynaptic alpha1-adrenergic blocking action, which is thought to account primarily for its effects.
Hypertension: Blockade of alpha1-adrenergic receptors by Doxazosin results in peripheral vasodilation, which produce a fall in blood pressure because of decreased peripheral vascular resistance.
Benign prostatic hyperplasia: Relaxation of smooth muscle in the bladder neck, prostate, and prostate capsule produced by alpha1-adrenergic blockade results in a reduction in urethral resistance and pressure, bladder outlet resistance, and urinary symptoms.
Pharmacokinetics: Absorption: Well-absorbed from gastrointestinal tract; bioavailability is about 65%.
Protein binding: Very high (98 to 99%).
Biotransformation: Metabolized extensively in the liver. Although several active and inactive metabolites have been identified (2-piperazinyl, 6' and 7'-hydroxy, 6' and 7'-O-desmethyl, and 2-amino), there is no evidence that they are present in substantial amounts.
Half-life: Elimination: 19 to 22 hours; does not appear to be significantly influenced by age or mild to moderate renal impairment.
Onset of action: Hypertension: 1 to 2 hours; there is a slight initial fall in blood pressure within the first hour, but the main hypertensive effect is apparent from 2 hours onwards. Benign prostatic hyperplasia (BPH): within 1 to 2 weeks.
Time to peak concentration: 1.5 to 3.6 hours.
Peak serum concentration: At steady state, there is a positive linear relationship between peak serum concentration and dose of Doxazosin. Following an oral dose of 1 mg Doxazosin, the standardized peak serum concentration was 9.6 mcg per L.
Time to peak effect: Antihypertensive: Single dose: 2 to 6 hours.
Duration of action: Antihypertensive: Single dose: 24 hours.
Elimination: Fecal: Unchanged drug, about 5%; metabolites, 63 to 65%. Renal: 9%. In dialysis: Doxazosin is not removed by hemodilaysis.
Indicated in the treatment of hypertension; Urinary outflow obstruction and the obstructive and irritative symptoms associated with benign prostatic hyperplasia (BPH). Obstructive symptoms are hesitation, intermittency, dribbling, weak urinary stream, and incomplete emptying of the bladder; while irritative symptoms include nocturia, daytime frequency, urgency, and burning.
Usual adult dose: Antihypertensive: Initial: 1 mg (base) once a day; Maintenance: The dosage being increased gradually to meet individual requirements; depending on periodic blood pressure measurements, dosage may be increased every two weeks, titrating upwards to 2, 4, 8, and 16 mg (base) once a day as needed and tolerated.
Note: Increases in dose beyond 4 mg (base) increase the likelihood of excessive postural effects including syncope, postural dizziness or vertigo, and postural hypotension. Geriatric patients may be more sensitive to the effects of the usual adult dose.
Benign prostatic hyperplasia: Initial: 1 mg (base) once a day. Dosage increases made to 2 mg and afterwards to 4 mg and 8 mg once daily should be titrated at one- to two-week intervals.
Usual adult prescribing limits: 16 mg once a day for hypertension.
8 mg once a day for BPH.
Usual pediatric dose: Safety and efficacy have not been established.
Risk-benefit should be considered when the following medical problems exist: Hepatic function impairment (although studies in patients with impaired hepatic function have not been done, Doxazosin is metabolized primarily in the liver, and, therefore, increased sensitivity or prolonged Doxazosin effect may occur).
Renal function impairment (small incidence of increased risk of first-dose orthostatic hypotensive reaction and prolonged hypotensive effect).
Sensitivity to Doxazosin.
Cross-sensitivity and/or related problems: Patients sensitive to other quinazolines (Prazosin, Terazosin) may also be sensitive to Doxazosin.
Carcinogenicity: In one 24-month chronic dietary administration study in rats, Doxazosin (given at a dose equivalent to 150 times the maximum recommended human dose) produced no evidence of carcinogenicity. In another similarly conducted study done in mice, up to 18 months of dietary administration produced no evidence of carcinogenicity. The latter study, however, did not use a maximally tolerated dose of Doxazosin.
Mutagenicity: There is no evidence of drug- or metabolic-related effects at either chromosomal or subchromosomal levels.
Fertility: Studies in rats given oral doses of 20 mg per kg of body weight (mg/kg) per day (equivalent to about 75 times the maximum recommended human dose) have shown that Doxazosin reduces fertility in male rats. The effect was reversible after 2 weeks of discontinuation of treatment.
Use in Children: No information is available on the relationship of age to the effects of Doxazosin in pediatric patients. Safety and efficacy have not been established.
Use in Elderly: A study performed in approximately 2000 hypertensive patients older than 65 years of age did not demonstrate geriatrics-specific problems that would limit the usefulness of Doxazosin in the elderly. However, the hypotensive effect of Doxazosin may be more pronounced in elderly hypertensive individuals, and lower daily maintenance doses may be required. Experienced with use of Doxazosin in elderly patients with benign prostatic hyperplasia (BPH) has shown that the safety profile of Doxazosin is similar to that in younger patients.
Breast-feeding: It is not known whether Doxazosin is distributed into breast milk. Problems in humans have not been documented.
However, in rats given a single oral dose of 1 mg/kg, Doxazosin accumulated in the milk of lactating rats with a maximum concentration about 20 times greater than the maternal plasma concentration.
Pregnancy: Adequate and well-controlled studies in humans have not been done.
Studies in rabbits and rats given daily oral doses of 40 and 20 mg/kg, respectively, have shown no evidence of harm to the fetus. The rabbit study, however, did not use a maximally tolerated dose of Doxazosin. Reduced fetal survival was associated with a dosage regimen of 82 mg/kg in rabbits. Following oral administration of labeled Doxazosin to pregnant rats, radioactivity was found to cross the placenta.
Studies in perinatal and postnatal rats given 40 or 50 mg/kg per day of Doxazosin revealed evidence of delayed postnatal development manifested by slower body weight gain and slightly later appearance of anatomical features and reflexes.
Those indicating need for medical attention:
Incidence more frequent: Dizziness; vertigo (dizziness or lightheadedness).
Incidence less frequent: Arrhythmias (irregular heartbeat); dyspnea (shortness of breath); orthostatic hypotension (dizziness or lightheadedness when getting up from a lying or sitting position; sudden fainting); palpitations (pounding heartbeat); peripheral edema (swelling of feet or lower legs); tachycardia (fast heartbeat).
Incidence rare: Priapism (painful or prolonged erection of the penis).
Those indicating need for medical attention only if they continue or are bothersome:
Incidence more frequent: Headache; unusual tiredness.
Incidence less frequent: Nausea; nervousness, restlessness, or unusual irritability; rhinitis (runny nose); somnolence (sleepiness or unusual drowsiness).
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), especially Indomethacin (antihypertensive effects of Doxazosin may be reduced when the medication is used concurrently with these agents; Indomethacin, and possibly other NSAIDs, may antagonize the antihypertensive effect by inhibiting renal prostaglandin synthesis and/or by causing sodium and fluid retention; the patient should be carefully monitored to confirm that the desired effect is being obtained).
Cimetidine (concurrent use may slightly increase the serum concentration of Doxazosin; however, the clinical significance of this increase is not known).
Hypotension-producing medications, other (antihypertensive effects may be potentiated when these medications are used concurrently with Doxazosin; although some antihypertensive and/or diuretic combinations are frequently used to therapeutic advantage, dosage adjustment are necessary during concurrent use).
Sympathomimetics (antihypertensive effects of Doxazosin may be reduced when it is used concurrently with these agents; the patient should be carefully monitored to confirmed that the desired effect is being obtained) (concurrent use of Doxazosin antagonizes the peripheral vasoconstrictrion produced by high doses of Dopamine).
Store at temperature not more than 30°C.
C02CA04 - doxazosin ; Belongs to the class of alpha-adrenoreceptor antagonists, peripherally-acting antiadrenergic agents. Used in the treatment of hypertension.
Tab 1 mg x 10 x 10's. 2 mg x 10 x 10's. 4 mg x 10 x 10's.