Terazosin was approved by the Food and Drug Administration (FDA) in 1987 initially as a treatment for hypertension and then approved in 1993 as a treatment for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia.[1][2] In more recent literature, terazosin, among other agents of its class been the subject of research as an off-label agent for the use of medical expulsive therapy (MET), a form of medical management for distal ureteral calculi.[3][4] The role of pharmacologic therapy in distal urinary tract stones is currently a focus of research, with terazosin and other alpha-1 antagonists under consideration for potential therapeutic value in addition to its traditionally accepted symptomatic relief effects[5]. Other off-label uses for terazosin currently being studied include alleviation of nightmares associated with post-traumatic stress disorder (PTSD),[6] antihidrotic in patients who have hyperhidrosis related to selective serotonin reuptake inhibitor (SSRI) use,[5] chronic prostatitis/chronic pelvic pain syndrome,[7] urethritis associated with radiation therapy, and idiopathic oligozoospermia.[8][9]

Terazosin is a selective, quinazoline-derived post-synaptic alpha-1 antagonist.[10][11] Alpha-1 adrenergic receptors subdivide into alpha-1A, alpha-1B, and alpha-1D.[12] Due to their nature as adrenergic receptors, they are a member of the G-protein coupled receptor category.  Terazosin is a competitive antagonist at these receptors, similar to other selective alpha-1 antagonists such as prazosin and doxazosin, notably at alpha-1A, which comprises the majority of alpha receptors in the urothelium.[13] The alpha-1 receptors are commonly located diffusely in smooth muscle tissue, including vascular smooth muscle, sphincter smooth muscle, and urinary bladder smooth muscle.[14] Alpha-1 adrenergic receptors are also present in many other organ systems, including the central nervous system, endocrine system, and gastrointestinal system. The primary anti-hypertensive action occurs by blocking vascular smooth muscle in the arterioles, and the anti-obstructive urinary tract effects result from smooth muscle relaxation in the ureters, bladder, and urethral sphincter.  The exertion of an anti-nightmare effect by terazosin does not have a clearly elucidated mechanism. However, a possible explanation could be because of the presence of presynaptic alpha-adrenergic receptors in the central nervous system.

Terazosin is available in the US in oral capsule formulation in the form of an HCl salt, available in 1 mg, 2 mg, 5 mg, and 10 mg formulations.

 For the FDA approved indications of hypertension and benign prostatic hyperplasia, the dosing route, frequency, and amount are as follows:

• Hypertension:

The initial dose is 1 mg to 10 mg orally daily, titrated upwards as needed to a maximum of 20 mg daily. Considered a second-line agent due to adverse effects, additional consideration as an agent if the patient also experiences lower urinary tract symptoms associated with benign prostatic hyperplasia.[15][16]

• Benign Prostatic Hyperplasia:

The initial dose is of 1 mg to 10 mg orally at bedtime, titrated upwards as needed based upon patient response up to 20 mg daily in 1 or 2 divided doses.[17]

 For Non-FDA approved indications, including medical expulsive therapy (MET), chronic prostatitis, hyperlipidemia, urethritis, hyperhidrosis, and oligospermia:

• Medical expulsive therapy for distal ureteral calculi:

2 mg to 10 mg orally at bedtime. Most studies have indicated usage of 2 mg to 5mg, and only rarely have 10 mg doses been cited. For MET, the typical duration of terazosin is for up to 2 weeks, and the patient may discontinue therapy following the expulsion of the stone.[3]

• Chronic Prostatitis/Chronic Pelvic Pain Syndrome:

1 mg to 5 mg orally daily for 14 weeks. Terazosin demonstrated effectiveness in a study comparing alpha-antagonist naïve patients with chronic prostatitis/chronic pelvic pain syndrome with a placebo.[7]

• Hyperlipidemia/Hypercholesterolemia:

5 mg, 10 mg, or 20 mg orally daily.  Studies demonstrating the lipid-lowering effects were subject to confounding factors due to titration of drug dosing to diastolic blood pressure or meeting maximum (20mg) dosage for terazosin. Additionally, there have not been studies to demonstrate a mortality benefit, as seen for other lipid-lowering drugs.[18][19]

• Idiopathic oligozoospermia:

2 mg orally daily. One clinical study by Gregoriou et al. demonstrated a statistically significant improvement in spermatozoa count and seminal fluid volume after treatment with six months of terazosin. However, the study noted no change in the mean percentage of abnormal spermatozoa and also did not detect any significant difference in pregnancy rates.[9]

• Urethritis associated with radiotherapy in prostate cancer

2 mg to 6 mg orally daily.  One study from Zelefsky et al. suggests an improvement in urinary tract symptoms associated with radiotherapy for localized prostate cancer.[20]

• Antidepressant-induced excessive sweating

1 mg to 6 mg orally daily.  A recent clinical trial demonstrated a positive response to hyperhidrosis associated with selective serotonin reuptake inhibitor use.[5]

Terazosin is generally well-tolerated. Many adverse effects of terazosin are explainable due to its blockade of alpha-1 adrenergic receptors.[16][11] Statistically significant adverse effects associated with terazosin detected in placebo-controlled trials listed in the FDA database include dizziness, headache, weakness, postural hypotension, and nasal congestion.[21][22] First-dose syncope is rare and may be mitigated by bedtime use. Orthostatic hypotension is common and should merit strong consideration when prescribing terazosin.[23] According to the FDA, post-marketing surveys also found priapism, atrial fibrillation, anaphylaxis, intraoperative floppy iris syndrome to be associated with terazosin use, though instances of such occurrences were extremely rare.

The only absolute contraindication to the usage of terazosin is allergy or hypersensitivity to the medication.  Relative contraindications include usage in geriatric populations due to the potential for patient harm associated with syncope and/or postural hypotension as a result of terazosin use, patients with heart failure as well as general intolerance of the adverse effects associated with terazosin as listed above.[24] It is important to note that in geriatric patient populations, the occurrence of syncope or orthostatic hypotension can lead to falls, which are associated with increased mortality, morbidity, loss of functional capacity, and institutionalization for diagnostic workup/rehabilitation related to the syncope.[25] Though not contraindicated for use in pediatric populations, caution is advised to due limited data available regarding the use of terazosin in children, though there are small studies of safe usage in children without adverse outcomes.[26][27][28]