Doxazosin dosing

The manufacturer of doxazosin notes that no adverse drug interaction has been seen between doxazosin and thiazides or furosemide7 However, they point out that doxazosin doses of greater then 4 mg daily increase the likelihood of adverse effects such as postural hypotension and syncope. ... 

Generally, arblockers are considered as second-line agents to be added on to most other agents when hypertension is not adequately controlled. They may have a specific role in the antihypertensive regimen for elderly males with prostatism however, their use is often curtailed by complaints of syncope, dizziness, or palpitations following the first dose and orthostatic hypotension with chronic use. The roles of doxazosin, terazosin, and prazosin in the management of patients with hypertension are limited due to the paucity of outcome data and the absence of a unique role for special populations or compelling indications from JNC 7. 

Requirement for up-titration of dose Yes (for terazosin and doxazosin immediate-release) no (for alfuzosin possibly for doxazosin extended-release and tamsulosin) No... 

Need for up-titration of daily dose. Up-titration is required for terazosin and immediate-release doxazosin. It is minimally required for extended-release doxazosin and tamsulosin. It is not required for extended-release alfuzosin. 

Dosage formulation. Immediate-release formulations of terazosin and doxazosin are quickly absorbed and produce high peak plasma levels. Modified- or extended-release formulations of doxazosin, alfuzosin, and tamsulosin produce lower peak levels, but more sustained therapeutic plasma levels, than immediate-release formulations and have less potential for producing hypotensive episodes, thereby allowing initiation of treatment with a therapeutic dose and once daily dosing.25-27... 

This system is the only osmotic system developed commercially at this time that is suitable for the oral administration of insoluble drugs to humans. It has been utilized in the development of several other drugs including isradipine, doxazosin, diltiazem, contraceptive steroids, glipizide, and verapamil [48-53], The system has also been utilized to codeliver the free bases of compounds normally administered as water-soluble salts such as pseudoephedrine and bromo-pheniramine [54], The latter system includes both a loading dose and a controlled release dose and is intended for applications in the over-the-counter market. 

Patients should be slowly titrated to a maintenance dose and should take these drugs at bedtime to minimize orthostatic hypotension and first-dose syncope with terazosin and doxazosin. Sample titration schedules for terazosin include ... 

Gillen water, J.Y. et al. 1995. Doxazosin for the treatment of benign prostatic hyperplasia in patients with mild to moderate essential hypertension A double-blind, placebo-controlled, dose-response multicenter study. J Urol. 154 110. 

First-dose effect Prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin,... 

The first-dose phenomenon may be minimized by limiting the initial dose to 1 mg of terazosin or prazosin (given at bedtime) or doxazosin. 

Doxazosin is well absorbed after oral administration and approximately two third of the dose is bioavailable. 

Prazosin, doxazosin, and terazosin are all efficacious in patients with BPH. These drugs are particularly useful in patients who also have hypertension. Considerable interest has focused on which -receptor subtype is most important for smooth muscle contraction in the prostate subtype-selective K1A-receptor antagonists might lead to improved efficacy and safety in treating this disease. As indicated above, tamsulosin is also efficacious in BPH and has relatively minor effects on blood pressure at a low dose. This drug may be preferred in patients who have experienced orthostatic hypotension with other -receptor... 

Prazosin Doxazosin Terazosin Block , but not a2 Lower BP Hypertension benign prostatic hyperplasia Larger depressor effect with first dose may cause orthostatic hypotension... 

Caution [C, ] CrCl <30 Contra Component sensitivity, asthma, severe COPD, sinus bradycardia Disp Soln SE Irritation, bitter taste, superficial keratitis, ocular allergic Rxn EMS Drug is absorbed systemically OD May cause electrolyte disturbances (K), acidosis and bradycardia monitor ECG Doxazosin (Cardura, Cardura XL) [Antihypertensive/Alpha Blocker] Uses HTN symptomatic BPH Action < [-Adrenergic blocker relaxes bladder neck smooth muscle Dose HTN Initial 1 mg/d PO may be T to 16 mg/d PO BPH Initial 1 mg/d PO, may T to 8 mg/d XR 2-8mg qAM Caution [B, ] Use w/ PDE5 inhibitor (eg, sildenafil) can cause 1 BP Contra Component sensitivity Disp Tabs SE Dizziness, HA, drowsiness, sexual dysfxn, doses >4 mg T postural BP risk Interactions T Effects W/ nitrates, antihypertensives, EtOH i effects W/ NSAEDs, butcher s broom -t effects OF clonidine EMS Concurrent EtOH use can T drowsiness syncope may occur w/in 90 min of initial dose OD May cause profound hypotension place pt in supine position, give IV fluids, use pressors if needed... 

Terazosin can often be given once daily, with doses of 5-20 mg/d. Doxazosin is usually given once daily starting at 1 mg/d and progressing to 4 mg/d or more as needed. Although long-term treatment with these -blockers causes relatively little postural hypotension, precipitous drop in standing blood pressure develops in a number of patients shortly after the first dose is absorbed. For this reason, the first dose should be small and should be administered at bedtime. While the mechanism of this first-dose phenomenon is not clear, it occurs more commonly in patients who are salt- and volume-depleted. 

Tadalafil has also been extensively evaluated in patients with cardiovascular disease and has a similar safety and efficacy profile to sildenafil (45). Studies have shown no adverse effects on cardiac contraction, ventricular repolarization, or ischemic threshold. A similar hypotensive effect has been recorded with a dose of doxazosin 8 mg so caution is needed. As hypotension does not occur in the supine position and as tadalafil has a long half-life it is suggested that tadalafil is taken in the morning and doxazosin in the evening. There is no interaction of tadalafil with the selective a-adrenoceptor antagonist tamsulosin, which can, therefore, be prescribed as an alternative to doxazosin for symptomatic benign prostate hypertrophy (46). 

Doxazosin (t/ 8h) was the first a-adrenoceptor blocker suitable for once daily prescribing. The first dose effect is also much less marked, although it is still advisable to start patients at a lower dose than is intended for maintenance. It is convenient, for instance, to prescribe 1 mg daily, increasing after 1 week to twice this dose without repeating the blood pressure measurement at this stage. A slow-release formulation, Cardura XL, can be started at the maintenance dose of 4 mg daily. 

A 64-year-old man developed a right hemiparesis after taking one dose of doxazosin 4 mg for prostatic symptoms. A CT scan of the brain and carotid ultrasound studies were normal. He recovered most of his neurological function within a few days. Ambulatory blood pressure monitoring after treatment with doxazosin 2 mg showed striking blood pressure reduction during sleep. 

Second-generation agents include prazosin, terazosin, doxazosin, and alfuzosin. These differ in terms of duration of action and dosing schedule. Whereas prazosin requires dosing two to three times a day, terazosin, doxazosin, and alfuzosin offer more convenient once-daUy dosing. Prazosin, terazosin, and doxazosin antagonize peripheral vascular ai-adrenergic receptors, in addition to those in the prostate, at the usual doses used to treat BPH. As a result, first-dose syncope, orthostatic hypotension, and dizziness are... 

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