SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Hytrin BPH 5 mg Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Active: Terazosin 5.0    mg/tablet

as monohydrochloride dehydrate    5.0

3    PHARMACEUTICAL FORM

Tablet.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Orally administered Hytrin BPH is indicated as a therapy for the symptomatic treatment of urinary obstruction caused by benign prostatic hyperplasia (BPH). Terazosin is a selective post synaptic alpha-1-adrenoreceptor antagonist. Antagonism of alpha-1-receptors on prostatic and urethral smooth muscle has been shown to improve urinary tract flow and relieve the urinary obstruction caused by BPH.

4.2    Posology and method of administration

Adults Only:

The dose of terazosin should be adjusted according to the patient's response. The following is a guide to administration:

Initial dose 1 mg before bedtime is the starting dose for all patients and should not be exceeded. Strict compliance with this recommendation should be observed to minimise acute first-dose hypotensive episodes.

Subsequent dose

The dose may be increased by approximately doubling at weekly or bi-weekly intervals to achieve the desired reduction in symptoms. The maintenance dose is usually 5 to 10 mg once daily. Improvements in symptoms have been detected as early as two weeks after starting treatment with terazosin.

At present there are insufficient data to suggest additional symptomatic relief with doses above 10 mg once daily.

Treatment should be initiated using the Hytrin BPH Starter Pack and response to treatment reviewed at four weeks. Transient side effects may occur at each titration step. If any side effects persist, consideration should be given to reducing the dose.

Use in renal insufficiency

Pharmacokinetic studies indicate that patients with impaired renal function need no alteration in the recommended dosages.

Use in Children

Use in children for BPH is not applicable.

Use in the Elderly

Pharmacokinetic studies in the elderly indicate that no alteration in dosage recommendation is required.

Postural Hypotension

Postural hypotension has been reported to occur in patients receiving terazosin for the symptomatic treatment of urinary obstruction caused by BPH. In these cases, the incidence of postural hypotensive events was greater in patients aged 65 years and over (5.6%) than those aged less than 65 years (2.6%)

4.3 Contraindications

Terazosin is contraindicated in patients known to be hypersensitive to alpha-adrenoreceptor antagonists.

4.4 Special warnings and precautions for use

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-blocker therapy before initiating use of phosphodiesterase-5-inhibitors.

In patients with benign prostatic hyperplasia Terazosin is not recommended for patients with a history of micturition syncope.

Terazosin decreases peripheral vascular resistance and since many patients with this disorder are elderly, careful monitoring of blood pressure during initial administration and during adjustment of dosage is recommended. The possibility of postural hypotension, or rarely, loss of consciousness, as reported in other patient groups should be borne in mind. Close observation is especially recommended. For patients taking medications that are known to lower blood pressure, Terazosin may augment the efficacy of antihypertensive therapy, consequently, close observation is especially recommended for patients taking medications that are known to lower blood pressure. Terazosin should not normally be administered to patients already receiving another alpha-1 -antagonist.

Sudden collapse may follow the initial dose of Terazosin.

In patients with congestive cardiac failure Terazosin is not recommended in the treatment of congestive cardiac failure due to mechanical obstruction such as aortic valve stenosis, mitral valve stenosis, pulmonary embolism and restrictive pericardial disease. Adequate data are not yet available to establish efficacy in patients with heart failure due to recent myocardial infarction.

When Terazosin is initially administered to patients with congestive cardiac failure who have undergone vigorous diuretic or other vasodilator treatment, particularly in higher than the recommended starting dose, the resultant decrease in left ventricular filling pressure may be associated with a significant fall in cardiac output and systemic blood pressure. In such patients, observance of the recommended starting dose of Terazosin followed by gradual dosage increase is particularly important.

The clinical efficacy of Terazosin in congestive cardiac failure has been reported to diminish after several months of treatment, in a proportion of patients. In these patients there is usually evidence of weight gain or peripheral oedema indicating fluid retention. Since spontaneous deterioration may occur in such severely ill patients, a causal relationship to Terazosin therapy has not been established. Thus, as with all patients with congestive cardiac failure, careful adjustment of diuretic dosage according to the patient's clinical condition is required to prevent excessive fluid retention and consequent relief of symptoms.

In those patients without evidence of fluid retention, when clinical improvement has diminished, an increase in the dosage of Terazosin will usually restore clinical efficacy.

In patients with hypertension A very small percentage of patients may respond in an abrupt and exaggerated manner to the initial dose of Terazosin. Postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness, has been reported, particularly with the commencement of therapy, but this effect is readily avoided by initiating treatment with a low dose of Terazosin and with small increases in dosage during the first one to two weeks of therapy. The effect when observed is not related to the severity of hypertension, is self-limiting and in most patients does not recur after the initial period of therapy or during subsequent titration steps.

4.5 Interaction with other medicinal products and other forms of interaction

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).

4.6 Pregnancy and lactation

Although no teratogenic effects were seen in animal testing, the safety of Hytrin use during pregnancy or during lactation has not yet been established. Hytrin should not be used therefore in pregnancy unless the potential benefit outweighs the risk.

4.7 Effects on 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.

4.8 Undesirable effects

Hytrin in common with other alpha-adrenoceptor antagonists 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 events reported with terazosin

The most common events were asthenia, palpitations, nausea, peripheral oedema, dizziness, somnolence, nasal congestion/rhinitis and blurred vision/amblyopia.

In addition, the following have been reported: back pain; headache; tachycardia; postural hypotension; syncope; oedema; weight gain; pain in extremities; decreased libido; depression; nervousness; paraesthesia; vertigo; dyspnoea; sinusitis and impotence.

Additional adverse reactions reported in clinical trials or reported during marketing experience but not clearly associated with the use of terazosin include the following: chest pain; facial oedema; fever; abdominal pain; neck pain; shoulder pain; vasodilation; arrhythmia; constipation; diarrhoea; dry mouth; dyspepsia; flatulence; vomiting; gout; arthralgia; arthritis; joint disorders; myalgia; anxiety; insomnia; bronchitis; epistaxis; flu symptoms; pharyngitis; rhinitis; cold symptoms; pruritis; rash; increased cough; sweating; abnormal vision; conjunctivitis; tinnitus; urinary frequency; urinary tract infection and urinary incontinence primarily reported in post-menopausal women.

At least two cases of anaphylactoid reactions have been reported with the administration of terazosin.

Post marketing experience: Thrombocytopenia and priapism have been reported. Atrial fibrillation has been reported: however, a cause and effect relationship has not been established.

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.

4.9 Overdose

Should administration of Hytrin lead to acute hypotension, cardiovascular support is of first importance. Restoration of blood pressure and normalisation of heart rate may be accomplished by keeping the patient in a supine position. If this measure is inadequate, shock should first be treated with volume expanders and if necessary, vasopressors could then be used. Renal function should be monitored and general supportive measures applied as required. Dialysis may not be of benefit since laboratory data indicate that terazosin is highly protein bound.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Studies suggest that alpha-1-adrenoreceptor antagonism is useful in improving the urodynamics in patients with chronic bladder obstruction such as in benign prostatic hyperplasia (BPH).

The symptoms of BPH are caused mainly by the presence of an enlarged prostate and by the increased smooth muscle tone of the bladder outlet and prostate, which is regulated by alpha-1-adrenergic receptors.

In in-vitro experiments, Hytrin has been shown to antagonise phenylephrine-induced contractions of human prostatic tissue. In clinical trials Hytrin has been shown to improve the urodynamics and symptomatology in patients with BPH

5.2    Pharmacokinetic properties

The plasma concentration of the parent drug is a maximum about 1 hour post administration and declines with a half-life of approximately 12 hours. Food has little or no effect on bioavailability. Approximately 40% of the administered dose is eliminated in the urine and 60% in the faeces. The drug is highly bound to plasma proteins.

5.3    Preclinical safety data

Carcinogenicity: Hytrin has been shown to produce tumours in male rats when administered at a high dose over a long period of time. No such occurrences were seen in female rats or in a similar study in mice. The relevance of these findings with respect to the clinical use of the drug in man is unknown.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose, maize starch, pregelatinised starch, purified talc, magnesium stearate and purified water.

6.2    Incompatibilities

None known.

6.3    Shelf life

36 months.

6.4    Special precautions for storage

None.

6.5 Nature and contents of container

Tablets in a blister pack. The 1mg tablets are only available as part of a starter pack. The starter pack consists of 7 x 1mg, 14 x 2mg and 7 x 5mg tablets. The blisters, of PVC/PVdC, are heat sealed with 20 micron hard tempered aluminium foil and packaged in a carton with a pack insert.

6.6 Special precautions for disposal

Not applicable.

7    MARKETING AUTHORISATION HOLDER

Amdipharm UK Limited

Regency House

Miles Gray Road

Basildon

Essex

SS14 3AF

United Kingdom.

8    MARKETING AUTHORISATION NUMBER(S)

PL 20072/0034

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

27/10/2006

10 DATE OF REVISION OF THE TEXT

10/09/2013