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URIZIDE BENDROFLUMETHIAZIDE TABLETS 5MG

Active substance(s): BENDROFLUAZIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
URIZIDE/Bendroflumethiazide

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Bendroflumethiazide BP 5 mg
Also contains lactose, for a full list of excipients see section 6.1.

3

PHARMACEUTICAL FORM
Tablet

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
URIZIDE is used in the treatment of oedema associated with mild or moderate
heart failure and for the treatment of mild or moderate hypertension.

4.2

Posology and method of administration
Posology
It is recommended that the tablets should be taken in the morning to avoid nocturia.
Adults and children aged 12 years and over:
Oedema: Initially 5 mg given orally once daily in the morning or on alternate days
usually produces the desired effect, but this dose can be increased to 10 mg if
required; maintenance dose 5 - 10 mg one to three times weekly.
Essential hypertension: 2.5-5 mg once daily in the morning. When
Bendroflumethiazide is used concurrently with other specific hypotensive agents, the
dosage of such agents should be reduced and then adjusted as necessary.

Children under 12 years:
Initially the dosage may be up to 400 micrograms/kg bodyweight daily, reducing to
50-100 micrograms/kg bodyweight daily for maintenance.
A more appropriate dosage form may be required.
Elderly:
Particular caution is needed in the elderly. Their dosage may need to be reduced,
particularly when renal function is impaired, because of their susceptibility to
electrolyte imbalance.
Route of administration: Oral.

4.3

4.4

Contraindications


Hypersensitivity to thiazides and any other ingredient in bendroflumethiazide
tablets



Severe renal or hepatic insufficiency



Addisons disease



Refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic
hyperuricaemia

Special warnings and precautions for use


Bendroflumethiazide may precipitate or aggravate diabetes mellitus and may
impair control of diabetes in patients receiving sulphonylureas.



Supplementary potassium is strongly recommended in patients receiving digitalis
who require prolonged diuretic treatment.



Treat with caution in patients with mild or moderate hepatic or renal impairment
(avoid if severe). Renal function should be monitored during
Bendroflumethiazide therapy. Thiazides can cause electrolyte imbalance which is
more severe in patients with hepatic and renal impairment and in those receiving
higher or prolonged doses. Patients on long term treatment and elderly patients
need blood tests to monitor blood electrolyte levels and blood dyscrasias. Lower
initial doses of diuretics should be used in the elderly, as they are particularly
susceptible to the side effects. May cause hypokalaemia, which may be corrected
by adding potassium supplements or a potassium-sparing drug to the regimen.



Increased risk of hypomagnesaemia in alcoholic cirrhosis.



May aggravate gout. Serum uric acid levels may be raised with or without gout in
some patients.



Treat with caution in porphyria.



May aggravate systemic lupus erythematosus.

4.5



Blood dyscrasias and pancreatitis have been reported.



Expectant mothers who receive thiazide diuretics may be at increased risk from
acute haemorrhagic pancreatitis; thrombocytopenia has been reported in newborn
infants following antepartum use of thiazides.



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

Interaction with other medicinal products and other forms of interaction


Allopurinol: Bendroflumethiazide may antagonise the action of allopurinol by
causing retention of urate in the kidney. Caution is advised when using this
combination.



Ulcer healing drugs: There is an increased risk of hypokalaemia and a decrease
in diuretic activity when carbenoxolone and bendroflumethiazide are taken
together. Patients should be monitored and given potassium supplements when
required.



Corticosteroids: Corticosteroids, ACTH, may exacerbate hypokalaemia
associated with bendroflumethiazide and its diuretic activity may be antagonised.



Acetazolamide: increased risk of hypokalaemia when thiazides and related
diuretics given with acetazolamide.



Antifungals: The risk of hypokalaemia is increased when amphotericin and
bendroflumethiazide are taken concurrently.



Antidepressants: There is an increased risk of postural hypotension if
bendroflumethiazide is given with tricyclic antidepressants. There may also be a
risk of hypokalaemia if thiazides are given with reboxetine. Concomitant use with
MAOIs may result in an enhanced hypotensive effect.



Sympathomimetics: Sympathomimetics can cause hypokalaemia. The risk of
serious heart arrhythmias in asthmatic patients may be increased if
bendroflumethiazide is added to their medication.



Theophylline:
Concomitant
administration
of
bendroflumethiazide increases the risk of hypokalaemia.



Antiarrhythmics: The cardiotoxicity of disopyramide, flecainide, amiodarone, and
quinidine is increased if hypokalaemia occurs following the administration of
bendroflumethiazide. The actions of lidocaine and mexiletine are antagonised by
hypokalaemia.



Antipsychotics: Hypokalaemia increases the risk of ventricular arrhythmias with
sertindole, pimozide and thioridazine, so concomitant use should be avoided.



Digoxin: The hypokalaemic effect of bendroflumethiazide may enhance
sensitivity to digoxin when taken concurrently. Patients should be monitored for
signs of digoxin intoxication, especially arrhythmias. The dose of digoxin should
be reduced and potassium supplements given, should digoxin toxicity develop.



Lithium: Bendroflumethiazide inhibits the tubular elimination of lithium,
resulting in an elevated plasma lithium concentration and risk of toxicity. Plasma

theophylline

and

lithium concentrations must be monitored when these drugs are given
concurrently.


Hormone antagonists: There is an increased risk of hyponatraemia when
bendroflumethiazide is used concomitantly with aminoglutethamide.
Bendroflumethiazide can cause an increased risk of hypercalcaemia when coadministered with toremifene



Antiepileptics: There is an increased risk of hyponatraemia
bendroflumethiazide and carbamazepine are taken concurrently.



Vitamins: The risk of hypercalcaemia is increased if bendroflumethiazide is given
with vitamin D.



Calcium salts: Bendroflumethiazide reduces urinary excretion of calcium so there
is an increased risk of hypercalcaemia when calcium salts are taken concurrently.
Serum calcium levels should be monitored to ensure that they do not become
excessive.



NSAIDs: Bendroflumethiazide may enhance the nephrotoxicity of NSAIDs.
Indometacin and ketorolac antagonise the diuretic effect of bendroflumethiazide,
this occurs to a lesser extent with ibuprofen, piroxicam and naproxen. The effects
of concurrent use should be monitored and the dose of bendroflumethiazide
modified if necessary.



Oestrogens and progestogens: Oestrogens and combined oral contraceptives
antagonise the diuretic effect of bendroflumethiazide.



Antidiabetics: Bendroflumethiazide antagonises the hypoglycaemic effects of
sulfonylureas (chlorpropamide), with a potential loss of diabetic control.



Muscle relaxants: The hypotensive activity of bendroflumethiazide may be
increased by baclofen and tizanidine. Bendroflumethiazide may enhance the
neuromuscular blocking activity of non-depolarising muscle relaxants, such as
tubocurarine, gallamine, alcuronium and pancuronium.



Antihypertensives: Bendroflumethiazide may enhance the antihypertensive effect
of ACE inhibitors, α and β- blockers, angiotensin-II antagonists and alprostadil.
There is an increased risk of first dose hypotension if prazosin is given to a
patient taking bendroflumethiazide.



Calcium channel blockers and peripheral vasodilators: The hypotensive effect
of, calcium channel blockers and moxisylyte may be enhanced when coadministered with bendroflumethiazide.



Nitrates: enhanced hypotension effect when diuretics given with nitrates



Cytotoxics: Concomitant use with cisplatin can lead to an increased risk of
nephrotoxicity and ototoxicity. Enhanced hypotensive effect when diuretics given
with aldesleukin



Levodopa: enhanced hypotension effect when diuretics given with levodopa.



Alcohol: enhanced hypotension effect when diuretics given with alcohol.



Anion exchange resins: Colestyramine and colestipol reduce absorption of
bendroflumethiazide. This can be prevented by leaving an interval of two hours
between doses of bendroflumethiazide and the anion exchange resin

when

4.6

4.7

Fertility, pregnancy and lactation
(i)

Diuretics are best avoided for the management of oedema of pregnancy or
hypertension in pregnancy as they crosses the placenta and their use may be
associated with hypovolaemia, increased blood viscosity and reduced
placental perfusion.

(ii)

There is inadequate evidence of safety in human pregnancy. Foetal bone
marrow depression and thrombocytopaenia as well as neonatal jaundice have
also been described.

(iii)

Bendroflumethiazide suppresses lactation and although the amounts passing
into breast milk are small, it should be avoided in mothers who wish to breast
feed.

Effects on ability to drive and use machines
As bendroflumethiazide can cause dizziness, patients should make sure they are not
affected before driving or operating machinery.

4.8

Undesirable effects
Effects on blood
Rarely, blood dyscrasias, including agranulocytosis,
thrombocytopenia and leucopenia, have been reported.

aplastic

anaemia,

Hypersensitivity reactions
Rashes (including exfoliative dermatitis), photosensitivity, pneumonitis and
pulmonary oedema have been reported occasionally.
Metabolic effects
Bendroflumethiazide may lower carbohydrate tolerance and the insulin dosage of
some diabetic patients may require adjustment. Care is required when
bendroflumethiazide is administered to patients with a known predisposition to
diabetes. Bendroflumethiazide may raise serum uric acid levels and exacerbate gout
in susceptible individuals. Plasma lipids may be altered in patients taking
bendroflumethiazide.
Effects on electrolytes
Bendroflumethiazide administration may cause hypokalaemia, hyponatraemia,
hypomangnesaemia, hypercalcaemia and hypochloraemic alkalosis. Hypokalaemia
may result in polyuria, malaise, muscle weakness or cramp, dizziness, nausea,
anorexia or vomiting.
Gastrointestinal effects
Nausea, vomiting, diarrhoea, constipation and gastric irritation have all been reported.
Other reactions

Pancreatitis, intrahepatic cholestasis and impotence (reversible on withdrawal of
treatment) have been reported. Postural hypotension or dizziness may also occur.

4.9

Overdose
Symptoms: Nausea, vomiting, diarrhoea, dehydration, dizziness, weakness, muscle
cramps, diuresis, increased frequency of micturition with polyuria and thirst. Extreme
cases may show depletion of intravascular volume, hypotension and peripheral
circulatory failure. Hypokalaemia and mild hypoglycaemia are likely to be present if
diuresis is profound. CNS depression (e.g. drowsiness, lethargy and coma) may occur
without cardiovascular or respiratory depression.
Treatment: Activated charcoal may help reduce absorption of substantial amounts if
given within one hour of ingestion. Treatment should be symptomatic and directed at
fluid and electrolyte replacement which should be monitored together with the blood
pressure and renal function. Hyponatraemia should be treated with water deprivation
rather than by the administration of sodium chloride. Cathartics should be avoided.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Bendroflumethiazide exhibits its diuretic effect predominantly as a result of
inhibition of sodium reabsorption from the distal convoluted tubule (cortical
diluting segment). The maximum rate of sodium excretion induced by
Bendroflumethiazide approaches 10%. Bendroflumethiazide reduces vascular
reactivity to both angiotensin II and to noradrenaline. It is believed that
Bendroflumethiazide has a direct action on resistance vessels.
Bendroflumethiazide reduces the renal excretion of calcium.

5.2

Pharmacokinetic properties
Bendroflumethiazide is completely absorbed after oral administration. Plasma
concentration peaks at 2 hours and is not greatly affected by food.
Plasma elimination half-life averages 8.5 hours. About 30% of the drug is
excreted unchanged in the urine while 70% is metabolised. Plasma protein
binding is high and the drug has a moderately high volume of distribution.

5.3

Preclinical safety data
Not applicable.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose
Maize starch
Pregelatinised maize starch
Sodium starch glycollate
Magnesium stearate

6.2

Incompatibilities
None known.

6.3

Shelf life
3 years.

6.4

Special precautions for storage
Do not store above 25°C. Keep the container tightly closed. Store in the
original container.

6.5

Nature and contents of container
High density polystyrene with polythene lids and/or polypropylene containers
with polythene lids and polyurethane or polythene inserts.
Pack sizes: 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000 tablets.

6.6

Special precautions for disposal
No special precautions

7

MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
11 Boumpoulinas Street,
3rd floor, 1060 Nicosia
Cyprus

8

MARKETING AUTHORISATION NUMBER(S)
PL 33414/0013

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23/02/2007

10

DATE OF REVISION OF THE TEXT
23/01/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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