Terazosin

G04C - Drugs used in benign prostatic hypertrophy ATC G04CA03 Small molecule approved 1987 Oral Natural product

JFDA label: Terastat tablet

Mechanism of Action

Alpha1-specific blocking agent with minimal alpha2 effects; this allows peripheral postsynaptic blockade, with the resultant decrease in arterial tone, while preserving the negative feedback loop which is mediated by the peripheral presynaptic alpha2-receptors; terazosin relaxes the smooth muscle of the bladder neck, thus reducing bladder outlet obstruction

Indications

Approved

Benign prostatic hyperplasia
Hypertension

Off-label

Pediatric hypertension
Ureteral calculi (distal)

Contraindications

Source: Lexicomp

Hypersensitivity to terazosin or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (5)

Common orthostatic hypotension · palpitations · Peripheral edema · syncope · tachycardia

Nervous system disorders (5)

Very Common Dizziness · myasthenia

Common Drowsiness · paresthesia · vertigo

Renal and urinary disorders (1)

Common Impotence

Metabolism and nutrition disorders (2)

Common Decreased libido · weight gain

Gastrointestinal disorders (1)

Common Nausea

Musculoskeletal and connective tissue disorders (2)

Common back pain · Limb pain

Eye disorders (1)

Common Blurred vision

Respiratory, thoracic and mediastinal disorders (3)

Common dyspnea · Nasal congestion · sinusitis

Dosing

Source: Lexicomp

Note: If terazosin is discontinued for several days or longer, consider beginning with initial dose and retitrate as needed. Benign prostatic hyperplasia: Oral: Initial: 1 mg at bedtime; thereafter, titrate upwards, if needed, over several weeks, balancing therapeutic benefit with terazosin-induced postural hypotension; most patients require 10 mg once daily; if no response after 4 to 6 weeks of 10 mg/day, may increase to 20 mg/day (maximum: 20 mg/day). Hypertension: Oral: Initial: 1 mg at bedtime; slowly increase dose to achieve desired blood pressure, up to 20 mg/day; usual dosage range (ASH/ISH [Weber 2014]: 1 to 2 mg daily. Note: Daily dosage may be divided and given as a twice-daily regimen if response is diminished at 24 hours and hypotension is observed at 2 to 4 hours following a dose. Ureteral calculi (distal) (off-label use): Oral: 2 to 5 mg at bedtime for up to 2 weeks or until stone expulsion; may be used as adjunctive therapy to shock wave lithotripsy (Gurbuz 2011; Wang 2009).

(For additional information see "Terazosin: Pediatric drug information") Hypertension (off-label use): Children and Adolescents: Oral: Initial: 1 mg once daily typically administered at bedtime; slowly increase dose to achieve desired blood pressure as tolerated; maximum daily dose: 20 mg/day (NHBPEP 2004; NHLBI 2011).

Refer to adult dosing. In the management of hypertension, consider lower initial doses (eg, immediate release: 0.5 mg once daily) and titrate to response (Aronow, 2011).

No dosage adjustment necessary. Hemodialysis: 10% dialyzable; supplemental dose not necessary.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Floppy iris syndrome

Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery. May require modifications to surgical technique.

Orthostatic hypotension/syncope

May cause significant orthostatic hypotension and syncope, especially with first dose or first few days of therapy; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE-5 inhibitor is introduced.

Priapism

Priapism has been associated with use (rarely); seek immediate medical assistance for erections lasting longer than 4 hours. Disease-related concerns:

Heart failure

In a scientific statement from the American Heart Association, terazosin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]). Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warning/precautions:

Appropriate use

BPH: Rule out prostatic carcinoma before beginning therapy (many symptoms of BPH and prostate cancer are similar).

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have not been observed in animal studies. Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are generally preferred (ACOG 2013).

Lactation

It is not known if terazosin is excreted in breast milk. The manufacturer recommends that caution be exercised when administering terazosin to nursing women.

Monitoring

Clinical pearl	Standing and sitting/supine blood pressure, especially following the initial dose at 2-4 hours following the dose and thereafter at the trough point to ensure adequate control throughout the dosing interval; urinary symptoms

Chemistry & Properties

Formula	C19H25N5O4
Molecular weight	387.44 g/mol
IUPAC name	[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(oxolan-2-yl)methanone
CAS	63590-64-7
PubChem CID	5401
InChIKey	`VCKUSRYTPJJLNI-UHFFFAOYSA-N`
logP	1.06 (XLogP 1.4)
Polar surface area	103.04 Å²
H-bond acceptors / donors	8 / 1
Drug-likeness (QED)	0.83
Lipinski violations	0

SMILES

COc1cc2nc(N3CCN(C(=O)C4CCCO4)CC3)nc(N)c2cc1OC

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Receptor binding (top 6)

Target	Action	Affinity
adrenergic Alpha1D (ADRA1D)	Binding	pKi 9.2
adrenergic Alpha1B (ADRA1B)	Binding	pKi 8.9
alpha1B	Binding	pKi 8.8
adrenergic Alpha1A (ADRA1A)	Binding	pKi 8.7
adrenergic Alpha1	Binding	pKi 8.1
alpha1A	Binding	pKi 7.3

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MRP2 (Substrate)OCT1 (Substrate)P-gp (Substrate)

Drug–drug interactions (50, DDInter)

Interacting drug	Severity	Management
Aldesleukin	moderate
Alimemazine	moderate
Amifostine	moderate
Betamethasone	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Budesonide	moderate
Bupropion	moderate
Canagliflozin	moderate
Codeine	moderate
Corticotropin	moderate
Dapagliflozin	moderate
Deflazacort	moderate
Dexamethasone	moderate
Diphenhydramine	moderate
Doxepin	moderate
Doxepin (topical)	moderate
Dronabinol	moderate
Empagliflozin	moderate
Epoprostenol	moderate
Ertugliflozin	moderate
Ethanol	moderate
Fludrocortisone	moderate
Hydrocodone	moderate
Hydrocortisone	moderate
Iloprost	moderate
Mepyramine	moderate
Methdilazine	moderate
Methylprednisolone	moderate
Minoxidil (topical)	moderate
Morphine	moderate
Morphine (liposomal)	moderate
Nabilone	moderate
Nitrous acid	moderate
Olopatadine (nasal)	moderate
Opium	moderate
Ozanimod	moderate
Pentoxifylline	moderate
Prednisolone	moderate
Prednisone	moderate

Showing 40 of 50.

Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Terastat tablet	Tablet 1 mg	20 tab pack varies	Advanced Pharmaceutical Industry	4.720
Terastat tablet	Tablet 5 mg	20 tab pack varies	Advanced Pharmaceutical Industry	5.630
Terastat tablet	Tablet 1 mg	50 tab pack varies	Advanced Pharmaceutical Industry	11.210
Terastat tablet	Tablet 5 mg	50 tab pack varies	Advanced Pharmaceutical Industry	13.370