Triamterene
(British Approved Name, US Adopted Name, rINN)
Drug Nomenclature
Note. Compounded preparations of triamterene may be represented by the following names:
• Co-triamterzide (BAN) — triamterene 2 parts and hydrochlorothiazide 1 part (w/w)
• Co-triamterzide (PEN) — triamterene and hydrochlorothi-azide.
Pharmacopoeias. In China, Europe, Japan, and US.
European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Triamterene). A yellow, crystalline powder. Very slightly soluble in water and in alcohol. Protect from light.
The United States Pharmacopeia 31, 2008, and Supplements 1 and 2 (Triamterene). A yellow, odourless, crystalline powder. Practically insoluble in water, in chloroform, in ether, in benzene, and in dilute alkali hydroxides; very slightly soluble in alcohol, in acetic acid, and in dilute mineral acids; soluble 1 in 30 of formic acid and 1 in 85 of 2-methoxyethanol. Store in airtight containers. Protect from light.
Adverse Effects
As for Amiloride Hydrochloride. Triamterene has also been reported to cause photo sensitivity reactions, increases in uric acid concentrations, and blood dyscrasias. Renal calculi may occur in susceptible patients, and megaloblastic anaemia has been reported in patients with depleted folic acid stores such as those with hepatic cirrhosis. Reversible renal failure, due either to acute interstitial nephritis or to an interaction with NSAIDs (see under Interactions, below) has occurred.
Incidence of adverse effects. In a postmarketing surveillance study of 70 898 patients taking triamterene with hydrochlorothiazide the most common adverse effects were fatigue, dizziness, and nausea. Adverse effects necessitated withdrawal in 8.1 % of patients. A subgroup analysis of 21 731 patients indicated that hyperkalaemia was more common in elderly patients and in those with diabetes mellitus.
Effects on the blood. There have been case reports of pancytopenia associated with triamterene therapy. Some patients had hepatic cirrhosis and the antifolate activity of triamterene was considered responsible.
Effects on the kidneys. There have been a number of reports of renal calculi containing triamterene or its metabolites, generally in patients also taking hydrochlorothiazide. An abnormal urinary sediment was described which was thought to represent precipitated triamterene. These observations were expanded in a crossover study: abnormal urinary sediment was seen in 14 of 26 patients taking triamterene but in none taking amiloride. Triamterene and its metabolites were identified by others in 181 of 50 000 renal calculi. Triamterene either formed the nucleus of the stone or was deposited with calcium oxalate or uric acid. One-third of the 181 stones were entirely or mainly composed of triamterene and its metabolites and it was suggested that supersaturation of the urine with these substances could provide suitable nuclei for the crystallisation of calcium oxalate. However, other workers were unable to confirm this and suggested that triamterene and its metabolites could become incorporated into the protein matrix of existing stones. In addition, an epidemiological study found no evidence that triamterene use was associated with an increased incidence of renal stones. Some authors have therefore considered that there was not enough evidence to contra-indicate the drug in patients with a history of recurrent renal calculi.
Deposition of triamterene in the urine may also play a part in the development of interstitial nephritis, which was diagnosed in 4 patients also taking hydrochlorothiazide, over a period of 4 years.
Triamterene has also been associated with transient decline in renal function and the development of renal failure. Several mechanisms may be responsible including interstitial nephritis, intrarenal obstruction by crystalline deposits, and an interaction with NSAIDs (see under Interactions, below). Elderly patients may be particularly at risk.
Effects on the skin. Photodermatitis has been reported in a patient taking triamterene. Pseudoporphyria, possibly associated with exposure to sunlight, occurred in a patient with vitiligo during treatment with triamterene and hydrochlorothiazide.
Precautions
As for Amiloride Hydrochloride. Triamterene should also be given with caution to patients with hyperuricaemia or gout, or a history of renal calculi. Patients with depleted folic acid stores such as those with hepatic cirrhosis may be at increased risk of megaloblastic anaemia.
Triamterene may interfere with the fluorescent measurement of quinidine. It may slightly colour the urine blue.
Interactions
As for Amiloride Hydrochloride.
Digoxin. For a report of the effect of triamterene on digoxin.
Dopaminergics. For a report of increased amantadine toxicity associated with hydrochlorothiazide and triamterene.
NSAIDs. There have been several reports of renal failure in patients taking triamterene and NSAIDs. Both types of drug are nephrotoxic and in combination the effect appears to be additive. It has been suggested that the suppression of urinary pros-taglandins by NSAIDs could potentiate the nephrotoxic effects of triamterene.
NSAIDs may also antagonise the diuretic action of triamterene.
Pharmacokinetics
Triamterene is variably but fairly rapidly absorbed from the gastrointestinal tract. The bioavailability has been reported to be about 50%. The plasma half-life has been reported to be about 2 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. Triamterene crosses the placenta and may be distributed into breast milk.
Hepatic impairment. Triamterene clearance was markedly decreased in 7 patients with alcoholic cirrhosis and ascites. The diuretic effect lasted for up to 48 hours in cirrhotic patients compared with 8 hours in healthy controls.
Renal impairment. Urinary excretion of triamterene and its metabolite, hydroxytriamterene sulfate, was significantly reduced in patients with renal impairment and in the elderly whose renal function was reduced. Accumulation of the active metabolite was possible in patients with renal impairment.
Uses and Administration
Triamterene is a weak diuretic with potassium-sparing properties which has actions and uses similar to those of amiloride. It produces a diuresis in about 2 to 4 hours, with a duration of 7 to 9 hours. The full therapeutic effect may be delayed until after several days of treatment.
Triamterene adds to the natriuretic but diminishes the kaliuretic effects of other diuretics. It is mainly used, as an adjunct to thiazide diuretics such as hydrochlorothiazide and loop diuretics such as furosemide, to conserve potassium in those at risk from hypokalaemia during the treatment of refractory oedema associated with hepatic cirrhosis, heart failure, and the nephrotic syndrome. It is also used with other diuretics in the treatment of hypertension.
When triamterene is given alone in the treatment of oedema, the oral dosage range is 150 to 250 mg daily, given in 2 divided doses, after breakfast and lunch. Doses may be given on alternate days for maintenance therapy. More than 300 mg daily should not be given. Smaller doses are used initially when other diuretics are also given. When used with hydrochlorothiazide, for example, in the treatment of hypertension, an initial dose of 50 mg of triamterene daily may be used.
Potassium supplements should not be given.
Preparations
British Pharmacopoeia, 2008: Co-triamterzide Tablets; Triamterene Capsules;
The United States Pharmacopeia 31, 2008, and Supplements 1 and 2: Triamterene and Hydrochlorothiazide Capsules; Triamterene and Hydrochlorothiazide Tablets; Triamterene Capsules.
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
Australia: Dytac¤; Belgium: Dytac¤; Canada: Dyrenium¤; France: Teriam¤; Germany: Jatropur¤; Ireland: Dytac¤; Netherlands: Dytac; Spain: Urocaudal¤; Switzerland: Dyrenium¤; United Kingdom: Dytac; United States: Dyrenium
Multi-ingredient Preparations
Australia: Dyazide¤; Hydrene; Austria: Confit; Dehydrosin¤; Diucomb¤; Diurid¤; Dytide H; Hydrotrix; Inderal comp¤; Resaltex¤; Salodiur¤; Tardurol¤; Triamteren comp; Triamteren/HCT¤; Triastad HCT; Trioral/HCT; Belgium: Diucomb¤; Dyta-Urese¤; Dytenzide; Maxzide¤; Brazil: Diurana; Iguassina; Canada: Apo-Triazide; Dyazide¤; Novo-Triamzide; Nu-Triazide; Chile: Drinamil; Hidroronol T; Uren; Finland: Furesis comp; Uretren Comp; France: Cycloteriam¤; Isobar; Prestole; Germany: Beta-Nephral¤; Beta-Turfa; Betathiazid¤; Calmoserpin¤; cardiotensin¤; dehydro sanol tri; Diu Venostasin; Diu-Tonolytril¤; Diucomb; Diuretikum Verla; Diutensat comp¤; Diutensat¤; Diutrix¤; Dociteren; Dociton Dytide H¤; duradiuret; Dytide H; Esiteren¤; Furesis comp¤; Haemiton compositum¤; Hydrotrix; Hypertorr¤; Jenateren comp¤; Manimon¤; Neotri; Nephral; pertenso¤; Propra comp; Resaltex¤; Sali-Puren; Slimin¤; Thiazid-comp; Tri-Thiazid Reserpin; Tri-Thiazid; Triampur Compositum; Triamteren comp; Triamteren comp; Triamteren-H¤; Triamteren/HCT; Triamthiazid¤; Triarese; triazid; Tripranol¤; Turfa; Veratide; Hong Kong: Apo-Triazide; Dyazide; Triam-Co¤; Trizid¤; Ireland: Dyazide; Dytide¤; Frusene¤; Italy: Fluss 40; Triamteril Complex¤; Malaysia: Apo-Triazide; Mexico: Dyazide¤; Netherlands: Dyta-Urese; Dytenzide; Epitriam¤; New Zealand: Dyazide¤; Triamizide; Trizid¤; Portugal: Dyazide; Triam-Tiazida R; Russia: Apo-Triazide (Апо-триазид); Triam-Co (Триам-ко); Triampur Compositum (Триампур Композитум); South Africa: Dyazide; Loretic¤; Renezide; Urizide¤; Singapore: Apo-Triazide; Dyazide¤; Spain: Picten¤; Salidur; Triniagar¤; Urocaudal Tiazida¤; Switzerland: Diucomb¤; Dyazide; Dyrenium compositum; Hydrotrix¤; t/h-basan; Thailand: Dazid; Dinazide; Dyazide; Dyterene; Skezide¤; United Kingdom: Dyazide; Dytide; Frusene; Kalspare; Triamaxco¤; Triamco; United States: Dyazide; Maxzide
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