Terazosin

Concomitant use of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) and terazosin may lead to symptomatic hypotension in some patients. In order to minimise the risk for developing postural hypotension the patient should be stable on the alpha-adrenoceptor blocker therapy before initiating use of phosphodiesterase-5-inhibitors.

The terazosin dose should be titrated with particular caution in patients with impaired liver function since terazosin undergoes extensive hepatic metabolism and is mainly excreted by the biliary tract. As no clinical experience is available in patients with severe hepatic impairment, the use of terazosin is not recommended in these patients.

In patients receiving terazosin plus ACE inhibitors or diuretics the proportion reporting dizziness or related side effects was greater than in the total population of terazosin treated patients from clinical trials.

Caution should be observed when terazosin is administered with other antihypertensive agents, to avoid the possibility of significant hypotension. When adding terazosin to a diuretic or other antihypertensive agent, dosage reduction and retitration may be necessary.

In patients with severe coronary heart disease, a very rapid or excessive decrease in blood pressure can lead to an exacerbation of angina pectoris.

Due to the vasodilatory effect of terazosin, it should be administered with caution if the following cardiac conditions are present:

• Pulmonary oedema due to aortic or mitral valve stenosis
• High output cardiac insufficiency
• Right-sided cardiac insufficiency due to pulmonary embolism or pericardial effusion
• Left-sided cardiac insufficiency with low filling pressure

Terazosin hydrochloride was not teratogenic in either rats or rabbits when administered at oral doses up to 1330 and 165 times, respectively, the maximum recommended human dose. Fetal resorptions occurred in rats dosed with 480mg/kg/day, approximately 1330 times the maximum recommended human dose. Increased fetal resorptions, decreased fetal weight and an increased number of supernumerary ribs were observed in offspring of rabbits dosed with 165 times the maximum recommended human dose. These findings (in both species) were most likely secondary to maternal toxicity.

Although no teratogenic effects were seen in animal testing, the safety of terazosin use during pregnancy has not yet been established. Furthermore, data from animal studies show that terazosin may increase the duration of pregnancy. Therefore, terazosin should not be used in pregnancy unless the potential benefit outweighs the risk.

It is not known whether terazosin is excreted in breast milk. Because many drugs are excreted in breast milk, caution should be exercised when terazosin is administered to a nursing woman.

Terazosin tablets have a major influence on the ability to drive and use machines.

Dizziness, light-headedness or drowsiness may occur with the initial dose or in association with missed doses and subsequent reinitiation of terazosin therapy. Patients should be cautioned about these possible adverse effects and the circumstances in which they may occur and advised to avoid driving or hazardous tasks for approximately 12 hours after initial dose or when the dose is increased.

Terazosin in common with other alpha-adrenoceptor blockers may cause syncope. Syncopal episodes have occurred within 30 to 90 minutes of the initial dose of the drug. Syncope has occasionally occurred in association with rapid dosage increases or the introduction of another antihypertensive agent.

In clinical trials in hypertension, the incidence of syncopal episodes was approximately one percent. In most cases this was believed to be due to an excessive postural hypotensive effect although occasionally the syncopal episode has been preceded by a bout of tachycardia with heart rates of 120 to 160 beats per minute.

If syncope occurs the patient should be placed in a recumbent position and supportive treatment applied as necessary.

Dizziness, light-headedness or fainting may occur when standing up quickly from a lying or sitting position. Patients should be advised of this possibility and instructed to lie down if these symptoms appear and then sit for a few minutes before standing to prevent their recurrence.

These adverse effects are self-limiting and in most cases do not recur after the initial period of therapy or during subsequent re-titration.

Adverse drug effects reported with terazosin from multiple sources including clinical trials and spontaneous reports:

Blood and lymphatic system disorder: Thrombocytopenia

Immune system disorders: Anaphylactoid reaction

Psychiatric disorders: Depression, nervousness, anxiety, insomnia

Nervous system disorders: Dizziness, somnolence, headache, paraesthesia, vertigo

Eye disorders: Blurred vision, amblyopia, visual impairment, conjunctivitis

Ear and labyrinth disorders: Tinnitus

Cardiac disorders: Palpitations, tachycardia, arrhythmia, atrial fibrillation

Vascular disorders: Postural hypotension, syncope, vasodilatation

Respiratory, thoracic and mediastinal disorders: Nasal congestion, rhinitis, dyspnoea, sinusitis, bronchitis, epistaxis, flu symptoms, pharyngitis, cold symptoms, cough

Gastrointestinal system disorders: Nausea, abdominal pain, constipation, diarrhoea, dry mouth, dyspepsia, flatulence, vomiting

Skin and subcutaneous tissue disorders: Pruritus, rash, hyperhidrosis, angioedema

Musculoskeletal and connective tissue disorders: Back pain, pain in extremity, neck pain, shoulder pain, gout, arthralgia, arthritis, joint disorders, myalgia

Renal and urinary disorders: Pollakiuria, urinary tract infection and urinary incontincece (primarily reported in post-menopausal women).

Reproductive system and breast disorders: Libido decreased, erectile dysfunction, priapism

General disorders and administration site conditions: Asthenia, peripheral oedema, oedema, chest pain, face oedema, pyrexia

Investigations: Weight increased. Decreased haematocrit, decreased haemoglobin, decreased white blood cell count, decreased total protein and decreased blood albumin (suggestive of haemodilution)

Treatment with terazosin for up to 24 months had no significant effect on prostate specific antigen (PSA) levels.