Hytrin - Drug Monograph

Introduction

Hytrin (terazosin hydrochloride) is an alpha-1 adrenergic receptor antagonist primarily used in the management of hypertension and benign prostatic hyperplasia (BPH). As a selective alpha-1 blocker, it exerts its therapeutic effects through peripheral vasodilation and relaxation of smooth muscle in the prostate and bladder neck.

Mechanism of Action

Terazosin selectively blocks postsynaptic alpha-1 adrenergic receptors located in vascular smooth muscle and the prostate. This inhibition results in:

• Vasodilation of peripheral arteries and veins, reducing peripheral vascular resistance
• Relaxation of smooth muscle in the prostate capsule and bladder neck
• Decreased sympathetic tone without affecting cardiac output significantly

Indications

• Hypertension (alone or in combination with other antihypertensive agents)
• Symptomatic benign prostatic hyperplasia (BPH)
• Off-label: Raynaud's phenomenon, pheochromocytoma (preoperative management)

Dosage and Administration

• Initial dose: 1 mg at bedtime
• Maintenance: 1-5 mg once daily (maximum 20 mg/day)
• Titrate gradually over weeks based on response

• Initial dose: 1 mg at bedtime
• Maintenance: 5-10 mg once daily
• May require several weeks for optimal effect

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution
• Geriatric: Start with lowest dose
• Pediatric: Not recommended

Pharmacokinetics

• Absorption: Well absorbed orally (>90%), bioavailability ~90%
• Distribution: Volume of distribution 0.6 L/kg, 90-94% protein bound
• Metabolism: Hepatic via CYP3A4, minimal first-pass metabolism
• Elimination: Half-life 12 hours, excreted primarily in feces (60%) and urine (40%)
• Onset: Antihypertensive effect within 15 minutes, peak at 2-3 hours

Contraindications

• Hypersensitivity to terazosin or other quinazolines
• Concomitant use with phosphodiesterase-5 inhibitors in hypertension treatment
• Orthostatic hypotension
• Severe hepatic impairment

Warnings and Precautions

• First-dose effect: Significant hypotension and syncope may occur within 30-90 minutes of initial dose
• Orthostatic hypotension: Risk increased with volume depletion, diuretic use, or concurrent antihypertensives
• Intraoperative floppy iris syndrome: May occur during cataract surgery
• Priapism: Rare but requires immediate medical attention
• Cataract surgery: Inform surgeon about terazosin use
• Hepatic impairment: Monitor closely

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, itraconazole): Increased terazosin levels
• Other antihypertensives: Additive hypotensive effects
• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil): Profound hypotension
• NSAIDs: May reduce antihypertensive effect
• Estrogens: May decrease antihypertensive effect
• Beta-blockers: Enhanced first-dose hypotension

Adverse Effects

• Dizziness (19%)
• Headache (16%)
• Asthenia (11%)
• Postural hypotension (7%)
• Nasal congestion (6%)

• Syncope
• Priapism
• Severe orthostatic hypotension
• Angina exacerbation
• Palpitations
• Visual disturbances

Monitoring Parameters

• Blood pressure (standing and supine) at initiation and regularly thereafter
• Heart rate
• BPH symptoms (IPSS score) for efficacy assessment
• Orthostatic blood pressure changes
• Liver function tests (periodically)
• Serum electrolytes in patients on diuretics
• Adverse effect profile

Patient Education

• Take initial dose at bedtime to minimize first-dose effects
• Rise slowly from sitting or lying position to prevent dizziness
• Avoid alcohol and excessive heat exposure
• Do not drive or operate machinery until effects are known
• Report any dizziness, fainting, or prolonged erection
• Continue taking even if feeling well; hypertension often asymptomatic
• Do not stop abruptly without medical supervision
• Inform all healthcare providers about terazosin use, especially before surgery

References

1. FDA Prescribing Information: Hytrin (terazosin hydrochloride) 2. Chobanian AV, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003 3. Roehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol 2005 4. Michaels E. Terazosin in the treatment of hypertension and benign prostatic hyperplasia. J Clin Pharmacol 1995 5. Lepor H. Alpha blockers for the treatment of benign prostatic hyperplasia. Urol Clin North Am 1995 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Terazosin monograph 7. Martindale: The Complete Drug Reference. London: Pharmaceutical Press