Bendroflumethiazide 5mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Bendroflumethiazide 5mg.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablets for oral use.
White, circular flat faced tablets with bevelled edges, B 5 separated by a break line on one face and plain on the reverse.
4.1 Therapeutic indications
Bendroflumethiazide is a diuretic. The tablets are indicated for the treatment of essential hypertension and oedema associated with such conditions as nephrotic syndrome, cirrhosis of the liver, congestive heart failure and premenstrual syndrome.
Adults:
Oedema
Essential Hypertension
Pre-menstrual syndrome
Children:
Oedema
5-10mg daily in the morning initially. Maintenance: usually 2.5mg-5mg on only two or three days in the week. A single dose may be sufficient.
2.5mg in the morning. Doses above 2.5mg are rarely necessary.
2.5mg each morning for seven days before the period is due.
Up to 400^g per kg body weight daily initially, reducing to 50-100^g per kg for maintenance.
4.3 Contraindications
Bendroflumethiazide tablets are contraindicated in patients with known hypersensitivity to thiazides; hypercalcaemia, hyponatraemia, refractory hypokalemia, severe renal and hepatic insufficiency, symptomatic hyperuricaemia and Addison's.
4.4 Special warnings and precautions for use
Bendroflumethiazide should be used with caution in patients with mild to moderate hepatic or renal impairment (avoid if severe). Renal function should be continuously monitored during thiazide therapy. Thiazide diuretics may exacerbate or activate systemic lupus erythematosus in susceptible patients.
All thiazide diuretics can produce a degree of electrolyte imbalance, especially in patients with renal or hepatic impairment or when the dosage is high or prolonged. Serum electrolytes should be checked for abnormalities, particularly hypokalemia, and the latter corrected by the addition of a potassium supplement to the regimen. Aggravates diabetes and gout; increased risk of hypomagnesaemia in alcoholic cirrhosis.
Regular ongoing monitoring and blood tests are to be performed in elderly patients and patients who are on long term treatment with bendroflumethiazide.
This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Sensitivity to digitalis glycosides may be increased by the hypokalemic effect of concurrent bendroflumethiazide. Patients should be observed for signs of digitalis intoxication, in particular arrhythmias, and if these appear, the dosage of the digitalis glycoside should be temporarily reduced and a potassium supplement given to restore stability.
Serum lithium concentrations may be increased by concurrent use of thiazide diuretics.
Non-steroidal anti-inflammatory agents may blunt the diuretic and antihypertensive effects of thiazide diuretics. Diuretics may increase the risk of nephrotoxicity of NSAIDs.
Xanthines, beta-agonists, ACTH, corticosteroids, acetazolamide and carbenoxolone may exacerbate the hypokalemia associated with thiazide use. Thiazide diuretics may enhance the neuromuscular blocking effects of the nondepolarising muscle relaxants, e.g. tubocurarine.
Thiazides may enhance the effects of antihypertensive agents while postural hypotension associated with therapy may be enhanced by concomitant ingestion of alcohol, barbiturates or opioids.
Concomitant use of carbamazepine may increase the risk of hyponatraemia.
There is an increased risk of hyponatraemia if thiazides are given with amphotericin.
The risk of hypercalcaemia is increased by the concomitant intake of calcium salts or vitamin D preparations.
Concomitant use with cisplatin can lead to an increased risk of nephrotoxicity and ototoxicity.
The cardiac toxicity of disopyramide, amiodarone, flecainide and quinidine is increased if hypokalemia occurs. The action of lidocaine and mexiletine is antagonised by hypokalemia.
There is an increased risk of hyponatraemia when thiazides are used concomitantly with aminoglutethimide. Thiazides can cause an increased risk of hypercalcaemia with toremifene.
Colestipol and cholestyramine may reduce the absorption of thiazide diuretics and should therefore be given 2 hours prior to, or after the ingestion of bendroflumethiazide.
Calcium-channel blockers and moxisylyte can cause an enhanced hypotensive effect.
There is an increased risk of postural hypotension with tricyclic antidepressants. There may also be an increased risk of hypokalaemia if thiazides are given with reboxetine. Concomitant use with monoamine oxidase inhibitors (MAOIs), baclofen or tizanidine may also give an increased hypotensive effect.
Oestrogens and combined oral contraceptives may antagonise the diuretic effect of thiazides.
There is an increased risk of first-dose hypotensive effect of post-synaptic alpha-blockers such as prazosin.
Hypokalemia increases the risk of ventricular arrhythmias with pimozide or thioridazine, therefore, concomitant use should be avoided. Hypokalemia or other electrolyte imbalance also increases the risk of ventricular arrhythmias with terfenadine.
Bendroflumethiazide may interfere with a number of laboratory tests, including estimation of serum protein-bound iodine and tests of parathyroid function.
4.6 Fertility, pregnancy and lactation
Diuretics are best avoided for the management of oedema of pregnancy or hypertension in pregnancy as their use may be associated with hypokalemia, increased blood viscosity and reduced placental perfusion.
There is inadequate evidence of safety in human pregnancy and foetal bone marrow depression and thrombocytopenia has been described. Foetal and neonatal jaundice have also been described.
Bendroflumethiazide is secreted in mother's milk, therefore breast feeding should be avoided.
4.7 Effects on ability to drive and use machines
None stated.
4.8 Undesirable effects
All thiazide diuretics can produce a degree of electrolyte imbalance, e.g. hypokalaemia.
Thiazide diuretics may raise the serum uric acid levels with subsequent exacerbation of gout in susceptible subjects.
Thiazide diuretics sometimes lower carbohydrate tolerance and the insulin dosage of the diabetic patient may require adjustment. Care is necessary when bendroflumethiazide is administered to those with a known predisposition to diabetes.
Postural hypotension and mild gastrointestinal effects; hypokalemia, hypomagnesaemia, hyponatraemia, hypercalcaemia, hypochloraemic alkalosis, hyperuricaemia, gout, hyperglycaemia, and altered plasma lipid concentration. Less commonly, rashes, photosensitivity; blood disorders (including neutropenia and thrombocytopenia - when given in late pregnancy neonatal thrombocytopenia has been reported); pancreatitis, intrahepatic cholestasis, and hypersensitivity reactions (including pneumonitis, pulmonary oedema, severe skin reactions) also reported.
Blood dyscrasias including agranulocytosis, aplastic anaemia, thrombocytopenia and leucopenia, and pancreatitis have been reported with long term therapy may occur rarely. Impotence (reversible on withdrawal of treatment) or skin reactions may occur.
4.9 Overdose
Symptoms of overdosage include anorexia, nausea, vomiting, diarrhoea, diuresis, dehydration, hypotension, dizziness, weakness, muscle cramps, paresthesia, tetany, gastrointestinal bleeding, hyponatraemia, hypo- or hyperglycaemia, hypokalemia and metabolic alkalosis. Treatment should be symptomatic and supportive including the correction of fluid and electrolyte imbalance. In the case of recent ingestion, gastric lavage should be conducted. Blood pressure should also be monitored. There is no specific antidote.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: Low-Ceiling Diuretics,thiazides-ATC code: C03AA01
Bendroflumethiazide is a thiazide diuretic and reduces the reabsorption of electrolytes from renal tubules thereby increasing the excretion of sodium and chloride and subsequently of water. The excretion of other electrolytes, notably potassium and magnesium, is also increased. The excretion of calcium is reduced. Thiazides also reduce carbonic anhydrase activity so that bicarbonate excretion is increased, but this effect is generally small and does not appreciably alter the acid base balance or the pH of the urine. Thiazides also have a hypotensive effect, due to a reduction in peripheral resistance and enhance the effects of other antihypertensive agents.
5.2 Pharmacokinetic properties
Bendroflumethiazide may be completely absorbed from the gastrointestinal tract and it is fairly extensively metabolised. About 30% is excreted unchanged in the urine. The onset of diuretic action of the thiazides following oral administration occurs within two hours and the peak effect between three and six hours after administration. The duration of the diuretic action of bendroflumethiazide is between 18 and 24 hours. The onset of the hypotensive action is generally three or four days.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to those included in other sections.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate Pregelatinised maize starch Maize Starch Purified talc Magnesium stearate
6.2 Incompatibilities
None known
6.3 Shelf life
36 months in amber glass bottles.
36 months in polyethylene/polypropylene containers. 24 months in PVC/aluminium foil blister packs.
6.4 Special precautions for storage
Do not store above 25°C.Store in the original package. Keep the containers tightly closed.
6.5 Nature and contents of container
Amber glass bottles with a plastic cap containing 50 tablets.
Polypropylene or polyethylene containers containing 100, 250, 500, 1000 and bulk amount of tablets.
Blister packs of 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or 14, 28, 56, 84, 112 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Special Concept Development (UK) Limited,
Units 1-7 Colonial Way, Watford,
Hertfordshire, WD24 4YR United Kingdom.
8 MARKETING AUTHORISATION NUMBER(S)
PL 36722/0033
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11/08/2016
10 DATE OF REVISION OF THE TEXT
11/08/2016