HYTRIN Tablet Ref.[8192] Active ingredients: Terazosin

Terazosin hydrochloride, like other alpha-adrenoceptor blockers, can cause marked lowering of blood pressure, especially postural hypotension and syncope in association with the first dose or first few doses of therapy. A similar effect can be anticipated if therapy is interrupted for more than a few doses and then re-started. Syncope has also been reported with other alpha-adrenoceptor blockers in association with rapid dosage increases or the introduction of another antihypertensive drug. Syncope is believed to be due to an excessive postural hypotensive effect, although occasionally the syncopal episode has been preceded by a bout of severe supraventricular tachycardia with heart rates of 120 to 160 beats per minute.

In clinical trials, the incidence of postural hypotension was greater in BPH patients than in those with hypertension. In these cases, the incidence of postural hypotension events was greater in patients aged 65 years and over (5.6%) than those aged less than 65 years (2.6%).

If administration is discontinued for more than several days, therapy should be re-instituted using the initial dosing regimen.

Due to the risk of an excessive decrease in blood pressure, caution is advised for the concomitant administration of terazosin and thiazides or other antihypertensive medications. If a thiazide diuretic or another antihypertensive medication is added during treatment with terazosin, the terazosin dose must be reduced or the drug discontinued. A new dose-titration is essential. When administering terazosin in addition to other antihypertensives, the dose of the other antihypertensives should be reduced before commencement of therapy and adjusted after discontinuation of terazosin.

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

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

Laboratory Tests

Small but statistically significant decreases in haematocrit, haemoglobin, white blood cells, total protein and albumin were observed in controlled clinical trials. These laboratory findings suggest the possibility of haemodilution. Treatment with terazosin for up to 24 months had no significant effect on Prostate Specific Antigen (PSA) levels.

Caution is also recommended, when terazosin is administered concomitantly with drugs, which may influence hepatic metabolism.

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 ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients on or previously treated with tamsulosin. Isolated reports have also been received with other alpha-adrenoceptor blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during cataract operation current or past use of alpha-adrenoceptor blockers should be made known to the ophthalmic surgeon in advance of surgery.

Hytrin 2mg Tablets contain lactose

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Hytrin 2mg Tablets contain colouring agent quinoline yellow aluminium lake E104

May cause allergic reactions.

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.

Terazosin has been given without interaction with analgesics/anti-inflammatories, cardiac glycosides, hypoglycemics, antiarrhythmics, anxiolytics/sedatives, antibacterials, hormones/steroids and drugs used for gout.

Phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) (see section 4.4).

Pregnancy

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 Hytrin use during pregnancy or during lactation has not yet been established. Furthermore, data from animal studies show that terazosin may increase the duration of pregnancy or inhibit labour. Therefore, Hytrin should not be used in pregnancy unless the potential benefit outweighs the risk.

Breast-feeding

It is not known whether terazosin hydrochloride is excreted in breast milk. Because many drugs are excreted in breast milk, caution should be exercised when terazosin hydrochloride 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 Hytrin 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.

Hytrin 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.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.

Not applicable.