1. Name Of The Medicinal Product
Hytrin BPH 10mg Tablets
2. Qualitative And Quantitative Composition
mg/tablet | ||
Active: | Terazosin
| 10.0 |
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 10mg 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 10mg 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
As with other alpha adrenoreceptor antagonists, terazosin is not recommended in patients with a history of micturition syncope.
In clinical trials, the incidence of postural hypotension was greater in patients who received terazosin for BPH than in patients who received terazosin for hypertension. In this indication 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%).
If administration is discontinued for more than several days, therapy should be re-instituted using the initial dosing regimen.
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.
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-1 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-1 blockers should be made known to the ophthalmic surgeon in advance of surgery.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
In patients receiving terazosin for BPH, 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, hypoglycaemics, 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 during pregnancy and 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 events and the circumstances in which they may occur and advised to avoid driving or hazardous tasks for approximately the first 12 hours after the initial dose or when the dose is increased.
4.8 Undesirable Effects
Hytrin, in common with other alpha-adrenoreceptor 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 studies 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 given supportive treatment 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 re-occurrence.
These adverse effects are self limiting and, in most cases, do not recur after the initial period of therapy or during subsequent 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 severe 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 terazosin 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, terazosin has been shown to antagonise phenylephrine-induced contractions of human prostatic tissue. In clinical trials terazosin 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 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: terazosin has been shown to produce benign adrenal medullary tumours in male rats when administered in very high doses over a long period of time. No such findings 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
Purified water
Dye blue (FD&C No.2 lake).
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 10mg tablets are supplied in packs of 28 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 And Other Handling
Not applicable
7. Marketing Authorisation Holder
Amdipharm plc
Regency House
Miles Gray Road
Basildon
Essex
SS14 3AF
8. Marketing Authorisation Number(S)
PL 20072/0035
9. Date Of First Authorisation/Renewal Of The Authorisation
20/05/98/ 02/12/2005
10. Date Of Revision Of The Text
June 2009
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