Co-Triamterzide Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-Triamterzide Tablets 50/25mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 50mg of Triamterene BP and 25mg of Hydrochlorothiazide BP.
3. PHARMACEUTICAL FORM
Tablets
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Co-Triamterzide tablets are recommended for the control of oedema in cardiac failure, cirrhosis of the liver or the nephrotic syndrome. It is also indicated in the treatment of mild to moderate hypertension, alone or in combination with other antihypertensive drugs.
4.2 Posology and method of administration
Co-Triamterzide tablets are intended for oral administration.
Adults Only
Hypertension: Initially 1 tablet a day after the morning meal, thereafter adjusted to the patient’s needs. If Co-Triamterzide is added to already established therapy with another antihypertensive drug, the dosage of the latter should be reduced, and later adjusted if necessary. If another antihypertensive drug is added to the Co-Triamterzide therapy, the dosage of the latter will not normally be reduced.
Oedema: The usual starting dosage is 1 Co-Triamterzide tablet twice a day after meals. The optimal dosage may be 3 tablets a day, 2 after breakfast and 1 after lunch. Maintenance dosage: One a diuresis has been established, dosage should be reduced. Usually 1 tablet a day, or two tablets on alternate days will suffice.
A dosage of 4 tablets a day should not be exceeded; at this level adverse reactions such as raised blood urea are more likely.
Elderly
The recommended adult dosage is appropriate. The normally occurring reduction in glomerular filtration with age should be borne in mind.
4.3 Contraindications
Do not give Co-Triamterzide tablets to patients with hyperkalaemia, progressive renal failure, increasing hepatic dysfunction, hypercalcaemia, diabetic ketoacidosis, Addision’s disease or known hypersensitivity to either constituent of the product. Potassium supplements, or other potassium-conserving drugs, should not be given routinely with Co-Triamterzide.
4.4 Special warnings and precautions for use
Use Co-Triamterzide with caution in patients with hepatic or renal insufficiency, in those predisposed to gout since both components can elevate uric acid levels; and in diabetic patients since thiazide diuretics can provoke hyperglycaemia and glycosuria.
After the first week, it is advisable to determine blood urea, electrolytes and serum potassium levels periodically, particularly in the elderly, those with renal insufficiency and those receiving concomitant treatment with NSAID’s.
4.5 Interactions with other medicinal products and other forms of interaction
Potassium supplements, or other potassium-conserving drugs, should not be given routinely with Co-Triamterzide tablets.
There may be increased responsiveness to tubocurarine. Cholestyramine may delay or reduce the absorption of many drugs including diuretics.
Caution should be exercised if Co-Triamterzide is used in conjunction with hypotensive agents. Also use with caution in conjunction with corticosteroids since an additive effect may result in excess potassium loss: with cardiac glycosides and antiarrhythmic drugs whose toxicity potential is enhanced by hypokalaemia which may result from diuretic treatment; and with carbenoxolone which may antagonise the diuretic action of Co-Triamterzide.
4.6 Pregnancy and lactation
Co-Triamterzide tablets have been in clinical use for a number of years, and there is no experimental or clinical evidence to suggest associated foetal abnormalities. Nevertheless, triamterene and thiazides have been shown to pass through the placenta and also into breast milk. In rare instances, thrombocytopenia, pancreatitis or hypoglycaemia have been reported in newborn infants of mothers treated with thiazides. The use of Co-Triamterzide in pregnant or nursing mothers should therefore be avoided unless essential.
Folate antagonists combined with triamterene are inadvisable during pregnancy because of the increased theoretical risk of folate deficiency.
4.7 Effects on ability to drive and use machines
Co-Triamterzide tablets are unlikely to affect the ability to drive or operate machinery.
4.8 Undesirable effects
Nausea, vomiting, diarrhoea, muscle cramps, weakness, dizziness, headache, dry mouth, undesirable decreases in blood pressure and rash have been reported. Photosensitivity is rare. Anaphylaxis is a remote possibility.
Minor serum electrolyte changes have been observed infrequently, and marked fluctuations in serum potassium levels are uncommon. Metabolic acidosis occasionally occurs. Electrolyte imbalance may also indicate excessive dosage or be secondary to the condition under treatment.
In common with most diuretics, Co-Triamterzide may reduce glomerular filtration rate and cause a temporary increase in blood urea level; again, this may also indicate excessive dosage or be secondary to the condition under treatment. It can also cause increases in plasma lipid levels.
Acute interstitial nephritis, reversed on stopping treatment, has been reported very rarely.
Rare cases of thrombocytopenic purpura and megaloblastic anaemia have been reported with triamterene; Thiazides alone have caused jaundice, acute pancreatitis and rarely blood dyscrasias including agranulocytosis, thrombocytopenia and leucopenia.
4.9 Overdose
Symptoms of electrolyte imbalance, hypotension, gastrointestinal disturbance and muscular weakness may occur. Treatment consists of the induction of vomiting and/ or gastric lavage, correcting fluid depletion and electrolyte imbalance, and symptomatic and supportive therapy. If hypotension persists after adequate fluid replacement, dopamine may be used. Renal dialysis may be of some benefit in cases of severe overdosage. There is no specific antidote.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Hydrochlorothiazide is a thiazide diuretic which reduces reabsorption of electrolytes from the renal tubules, thereby increasing the excretion of sodium and chloride ions, and consequently of water. Diuresis is initiated in about 2 hours and lasts for up to 12 hours. Potassium ions are excreted to a lesser extent. It also reduces carbonic-anhydrase activity so that bicarbonate excretion is increased, but this effect is generally small compared with the effect on chloride excretion and does not appreciably alter the acid-base balance or the pH of the urine.
Triamterene is a mild diuretic which appears to act mainly on the distal renal tubules. It produces a diuresis in about 2 to 4 hours reaching a maximum effect in about 7 to 9 hours. The full effect may be delayed until after several days of treatment. Like spironolactone, it increases the excretion of sodium and chloride and decreases the excretion of potassium. Unlike spironolactone however, it does not appear to act by inhibiting aldosterone. It slightly increases the excretion of bicarbonate though it does not appear to inhibit carbonic anhydrase activity.
Triamterene adds to the natriuretic but diminishes the kaliuretic effects of other diuretics and is mainly used as an adjunct to the thiazides, frusemide, and similar diuretics, to conserve potassium.
5.2 Pharmacokinetic properties
Hydrochlorothiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. It has been estimated to have a plasma half-life of about 5 hours with a subsequent longer terminal phase; its biological half-life is up to about 15 hours. It is excreted unchanged in the urine.
Triamterene is incompletely but fairly rapidly absorbed from the gastrointestinal tract. It has been estimated to have a plasma half-life between 90 minutes and 12 hours. It is estimated to be about 60% bound to plasma proteins. It is extensively metabolised and is mainly excreted in the urine in the form of metabolites with some unchanged Triamterene; variable amounts are also excreted in the bile.
5.3 Preclinical safety data
There are no preclinical safety data of relevance to the prescriber which are additional to those already included in other sections of the SPC.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Each tablet contains Lactose (Hydrous) BP, Maize Starch BP, Microcrystalline Cellulose BP, Povidone K30 BP, Disodium Edetate BP, Magnesium Stearate BP, Sodium Starch Glycollate BP and Sunset Yellow (E110).
6.2 Incompatibilities
There are no major incompatibilities.
6.3 Shelf life
36 months
6.4 Special precautions for storage
Store in a cool, dry place not exceeding 25°C.
6.5 Nature and contents of container
Polypropylene pots with white polyethylene caps and polyethylene ullage filler in packs of 100 and 500 tablets.
Instructions for use/handling
6.6
None.
7. MARKETING AUTHORISATION HOLDER
Generics [UK] Ltd Station Close Potters Bar Herts EN6 1TL
8. MARKETING AUTHORISATION NUMBER
PL 04569/0165
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date MA Granted: 4th November 1988 Last renewal date: 19th July 1994
10. DATE OF REVISION OF TEXT
12th April 1999
POM