HYTRIN TABLETS 5MG
Active substance(s): TERAZOSIN MONOHYDROCHLORIDE DIHYDRATE / TERAZOSIN MONOHYDROCHLORIDE DIHYDRATE / TERAZOSIN MONOHYDROCHLORIDE DIHYDRATE
NAME OF THE MEDICINAL PRODUCT
Hytrin 5 mg Tablets
Terazosin 5 mg Tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5 mg of terazosin as monohydrochloride dihydrate.
Excipients with known effect:
Lactose: (123.07 mg)
For a full list of excipients, see section 6.1.
Tan, round, flat bevelled tablets embossed with logo and triangular facets on
one face and plain on the other.
Orally administered Hytrin is indicated in adults for the treatment of mild to
moderate hypertension. It may be used in combination with thiazide diuretics
and/or other antihypertensive drugs or as sole therapy where other agents are
inappropriate or ineffective. The hypotensive effect is most pronounced on the
diastolic pressure. Although the exact mechanism of the hypotensive action of
terazosin is not established, the relaxation of peripheral blood vessels appears
to be produced mainly by competitive antagonism of post-synaptic alpha-1adrenoceptors. Hytrin usually produces an initial gradual decrease in blood
pressure followed by a sustained antihypertensive action.
Orally administered Hytrin is also indicated in adults as a therapy for the
symptomatic treatment of urinary obstruction caused by benign prostatic
hyperplasia (BPH). Terazosin is a selective post synaptic alpha-1-adrenoceptor
blocker. 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.
Posology and method of administration
Hytrin Tablets are not recommended for use in children. Safety and efficacy in
children has not been established.
Pharmacokinetic studies in the elderly indicate that no alteration in dosage
recommendation is required.
Use in renal insufficiency
Pharmacokinetic studies indicate that patients with impaired renal function
need no alteration in the recommended dosages.
Use in patients with hepatic insufficiency:
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.
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%)
Use with thiazide diuretics and other antihypertensive agents
When adding a thiazide diuretic or another antihypertensive agent to a
patient’s treatment regimen the dose of Hytrin should be reduced and
retitration carried out if necessary. Caution should be observed when Hytrin is
administered with thiazides or other antihypertensive agents as hypotension
Method of administration
Treatment should be initiated using the Starter Pack and response to treatment
reviewed at four weeks.
If administration is discontinued for more than several days, therapy should be
re-instituted using the initial dose titration regimen.
1mg before bedtime is the starting dose for all patients and should not be
exceeded. Compliance with this initial dosage recommendation should be
strictly observed to minimise potential for acute first-dose hypotensive
The single daily dosage may be increased by approximately doubling the
dosage at weekly intervals to achieve the desired blood pressure response.
The usual maintenance dose is 2mg to 10mg once daily. Doses over 20mg
rarely improve efficacy and doses over 40mg have not been studied.
The dose of terazosin should be adjusted according to the patient’s response.
The following is a guide to administration:
1mg 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.
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.
Hypersensitivity to the active substance or to any of the excipients listed in
Known sensitivity to other alpha-adrenoceptor blockers.
Patients with a history of micturition syncope.
Special warnings and precautions for use
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 alphaadrenoceptor 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.
Before treating the symptoms of benign prostatic hyperplasia (BPH) with
alpha-blockers, other causes of impaired urinary flow or urinary symptoms
should be excluded. Also where the diagnosis of BPH has been established, it
should be confirmed that there is no concomitant obstruction of the upper
urinary tract or any signs of infection before treating with terazosin. Patients
with benign prostatic hyperplasia, who simultaneously suffer from congestion
of the upper urinary tract, chronic urinary tract infection or bladder stones,
should not be treated with terazosin.
Terazosin should not be given to patients with bladder overflow, anuria or
advanced renal failure.
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
• 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 5mg Tablets contain lactose
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or glucose-galactose malabsorption should not take this
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).
Fertility, pregnancy and lactation
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.
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.
Effects on ability to drive and use machines
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
Immune system disorders
Depression, nervousness, anxiety, insomnia
Nervous system disorders
Dizziness, somnolence, headache, paraesthesia, vertigo
Blurred vision, amblyopia, visual impairment, conjunctivitis
Ear and labyrinth disorders
Palpitations, tachycardia, arrhythmia, atrial fibrillation
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,
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
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:
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.
ATC Code: G04CA03
Pharmacotherapeutic group: alpha-adrenoreceptor antagonists
Mechanism of action
Although the exact mechanism of the hypotensive action is not established, the
relaxation of peripheral blood vessels appears to be produced mainly by
competitive antagonism of post-synaptic alpha-adrenoceptors. Hytrin usually
produces an initial gradual decrease in blood pressure followed by a sustained
Clinical experience indicates that a 2-5% decrease in total cholesterol plasma
concentration and a 3-7% decrease in the combined LDLC + VLDLC fraction
plasma concentration from pretreatment values are associated with the
administration of therapeutic doses of terazosin.
In clinical trials, plasma concentrates of total cholesterol and combined low
density and very low density lipoproteins were found to be slightly reduced
following Hytrin administration. Additionally, the increase in total cholesterol
seen with other hypertensive agents did not occur when these were used in
combination with Hytrin.
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 pro static tissue. In clinical
trials terazosin has been shown to improve the urodynamics and
symptomatology in patients with BPH.
Terazosin is well absorbed (80-100%). Terazosin has a minimal “first pass”
effect and almost the complete dose of terazosin is systematically available.
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 90-94% of terazosin is bound to plasma proteins. Protein
binding is independent of total active substance concentrations.
Main metabolites of terazosin are caused by demethylation and conjugation.
Approximately 10% and 20% of orally administered terazosin is excreted as
unchanged active substance in urine and in faeces, respectively.
Approximately 40% of the administered dose is eliminated in the urine and
60% in the faeces. The drug is highly bound to plasma proteins.
Linearity / non-linearity of pharmacokinetics
After oral dosing of terazosin AUC and Cmax increase in proportion with dose
over the recommended dose range (2-10 mg).
Preclinical safety data
Preclinical data reveal no special hazards for humans based on conventional studies
of safety pharmacology.
No evidence of a genotoxic effect of terazosin has been reported from in vitro and in
vivo investigations of the mutagenic potential of the substance.
Decreased fertility and testicular atrophy were seen in rats at repeated administration
of doses ≥20-30 times higher than the maximum recommended human dose. Foetal
resorptions, decreased foetal weights, increased number of supernumerary ribs and
decreased post-natal survival were noted in reproductive toxicity studies in rats and
rabbits at maternally toxic doses (60-280 times the maximum recommended human
In male rats, terazosin induced benign adrenal medullary tumours at the highest
administered dose corresponding to 175 times the maximum human dose.
Carcinogenicity: In male rats, terazosin induced benign adrenal medullary tumours at
the highest administered dose corresponding to 175 times the maximum human dose.
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
List of excipients
Dye (iron oxide burnt sienna, E172)
Special precautions for storage
Nature and contents of container
Tablets in a blister pack. The 5mg tablets are supplied in a pack of 28 tablets.
Blisters are packaged in a carton with a package insert.
Starter pack for BPH:
Tablets in a blister 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.
Special precautions for disposal
No special requirements.
MARKETING AUTHORISATION HOLDER
Amdipharm UK Limited
85 King William Street
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
DATE OF REVISION OF THE TEXT
Source: Medicines and Healthcare Products Regulatory Agency
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