Triamteren

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Keep container tightly closed in a dry and well-ventilated place.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, dampen the solid spill material with 5% ammonium hydroxide, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% ammonium hydroxide to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% ammonium hydroxide followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for Triamterene (7 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for Triamterene (14 total), please visit the HSDB record page.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Oral bioavailability of hydrochlorothiazide from the original formulation (no longer commercially available) of Dyazide capsules was about 50-65% that from Maxzide tablets or single-entity tablets or solutions of the drug. In one crossover study in a limited number of healthy adults receiving single doses of the drug, the mean hydrochlorothiazide dose recovered in urine within 72 hours was about 30% for the original formulation of Dyazide capsules and about 60% for Maxzide or single-entity tablets of the drug. In 1995, Dyazide capsules were reformulated to improve the oral bioavailability of triamterene and hydrochlorothiazide. The oral bioavailabilities of triamterene and hydrochlorothiazide from the reformulated Dyazide capsules now are comparable to those of aqueous suspensions of the individual drugs, averaging 85 and 82%, respectively, for the new formulation and 100 and 100%, respectively, for the suspensions. In addition, intraindividual variation in bioavailability from the reformulated Dyazide capsules was reduced by about 40% compared with the original formulation. The manufacturer states that the reformulated Dyazide capsules also are bioequivalent to single-entity 25-mg hydrochlorothiazide tablets and 37.5-mg triamterene capsules. Administration of reformulated Dyazide with a high-fat meal in healthy adults increased the average bioavailabilities of triamterene by about 67%, 6-p-hydroxytriamterene by about 50%, and hydrochlorothiazide by about 17% and the peak concentrations of triamterene and its p-hydroxy metabolite and delayed the absorption of the active drugs by up to 2 hours.

Triamterene should not be used concurrently with another potassium-sparing agent (e.g., amiloride, spironolactone), since concomitant therapy with these drugs may increase the risk of hyperkalemia compared with triamterene alone. At least 2 deaths have been reported in patients receiving triamterene and spironolactone concurrently; in one patient, recommended dosages were exceeded and, in the other patient, serum electrolytes were not closely monitored. Potassium-sparing diuretics should be used with caution and serum potassium should be determined frequently in patients receiving an angiotensin-converting enzyme (ACE) inhibitor (e.g., captopril, enalapril), since concomitant administration with an ACE inhibitor may increase the risk of hyperkalemia. Dosage of triamterene should be reduced or the drug should be discontinued as necessary. Patients with renal impairment may be at increased risk of hyperkalemia.

In a three-way crossover study, 23 patients with hepatic cirrhosis, ascites, and dependent edema received 40 mg/day of furosemide alone and combined with triamterene 50 mg/day and triamterine 100 mg/day. Baseline potassium excretion did not increase when furosemide was given alone, but potassium excretion fell when 50 mg or 100 mg of triamterene was also given. Both doses of triamterene augmented the natriuretic effect of furosemide.

Concurrent administration of triamterene with potassium supplements, potassium-containing medications (e.g., parenteral penicillin G potassium), or other substances containing potassium (e.g., salt substitutes, low-salt milk) may increase the risk of hyperkalemia as compared with triamterene alone, and such combined use is contraindicated.

For more Interactions (Complete) data for Triamterene (11 total), please visit the HSDB record page.

Triamterene therapy has been associated with rare instances of idiosyncratic, clinically apparent liver injury which have invariably been mild and anicteric. The liver injury typically arises after 4 to 12 weeks of therapy and the pattern of serum enzyme elevations is usually hepatocellular or mixed. Fever is a prominent symptom and the reaction is often more typical of drug-fever than hepatotoxicity (Case 1). Rash and eosinophilia can occur, but are usually not prominent. Autoantibodies are rare. All published cases of triamterene associated liver injury have been self-limited in course and resolved rapidly upon withdrawal.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.1X10-11(SRC), determined from a structure estimation method(2), indicates that triamterene is expected to be immobile in soil(SRC). The pKa of triamterene is 6.23(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of triamterene from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.9X10-18 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). Triamterene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2018).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.5X10+5(SRC), determined from a structure estimation method(2), indicates that triamterene is expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.9X10-18 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). A pKa of 6.2(4) indicates triamterene will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 0.98(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2018).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), triamterene, which has an estimated vapor pressure of 1.1X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Triamterene absorbs UV light at 356 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The major side effects of triamterene include dizziness, fatigue, headache, dry mouth, hyperkalemia, and dehydration. Other common side effects include nausea, vomiting, rash, diarrhea, muscle cramps, weakness, xerostomia, azotemia, and hyperuricemia. Serious adverse effects include anaphylaxis, ventricular arrhythmias, hyperkalemia, drug-induced interstitial nephritis, acute renal failure due to nephrotoxicity, thrombocytopenia, megaloblastic anemia, and hepatotoxicity. Triamterene can also cause triamterene nephrolithiasis in patients with a history of previous kidney stones; these patients should avoid this drug.

IDENTIFICATION AND USE: Triamterene is epithelial sodium channel blocker, which is used as diuretic in human patients, as well as in veterinary medicine in dogs and cats. There is little experience associated with its use in dogs or cats and it is rarely recommended. HUMAN STUDIES: Overdosage of triamterene may cause electrolyte imbalance, especially hyperkalemia. Nausea, vomiting, other GI disturbances, and weakness may also occur. Hypotension may also result, especially when the drug is used concomitantly with hydrochlorothiazide or other diuretics or hypotensive agents. Mucosal ulceration and severe bone-marrow insufficiency with marked megaloblastic transformation occurred during treatment with triamterene in a patient with decompensated alcoholic liver cirrhosis and malnutrition. Two cases of triamterene crystalline nephropathy have been reported. Acute intravascular hemolysis and renal failure developed while a patient was taking triamterene. ANIMAL STUDIES: In the first study in mice, triamterene caused significant increases in the incidences of hepatocellular adenoma in females. In a second study, survival of exposed mice was similar to that of controls. There were significant increases in the incidence of hepatocellular adenoma in males and females, and of hepatocellular adenoma or carcinoma (combined) in females. The incidence of liver foci was increased in some groups of treated mice in both the first and second studies. Treatment with triamterene also caused treatment-related thyroid follicular cell hyperplasia. Triamterene caused a significant increase in the incidence of hepatocellular adenoma in male rats. Hepatocellular adenoma was present in all three dosed groups of males and not in males in the control group. There was no significant increase in the incidence of tumors in female rats. Reproduction studies have been performed in rats without evidence of harm to the fetus due to triamterene. Triamterene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation. It did not induce chromosomal aberrations in Chinese hamster ovary cells, with or without metabolic activation. Positive results were obtained for induction of sister chromatid exchanges in Chinese hamster ovary cells with and without metabolic activation.

Potassium-sparing diuretics overdose is relatively rare, and there are no reports of deaths. With mild to moderate toxicity, there can be the development of nausea, vomiting, diarrhea, mild dehydration, and hyperkalemia. If there is severe toxicity, there can be the development of severe dehydration coupled with hyperkalemia, which may lead to dysrhythmias, tachycardia, hypotension, hyperactive deep tendon reflexes, and possibly changes in mental status. Acute renal failure may also develop due to the deposition of triamterene in the renal tubules. Should there be any signs of toxicity, the clinician should immediately discontinue the drug.

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for triamterene is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]

Triamterene, exhibited a removal rate range of -37 to 2% in an urban sewage treatment plant in Dresdin Germany, sampled for 10 consecutive days in January/February, 2015(1). Triamterene exhibited an 18% detection frequency (median concentration 12.7 ng/L; maximum concentration of 14.9 ng/L) in final leachate from 22 landfills in the conterminous United States; sampled in 2011 (2 landfills) and 2012 (20 landfills)(2).

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of triamterene can be estimated to be 1.5X10+5(SRC). According to a classification scheme(2), this estimated Koc value suggests that triamterene is expected to be immobile in soil. The pKa of triamterene is 6.2(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/SIGNS AND SYMPTOMS/ Overdosage of triamterene may cause electrolyte imbalance, especially hyperkalemia. Nausea, vomiting, other GI disturbances, and weakness may also occur. Hypotension may also result, especially when the drug is used concomitantly with hydrochlorothiazide or other diuretics or hypotensive agents.

/CASE REPORTS/ Mucosal ulceration and severe bone-marrow insufficiency with marked megaloblastic transformation occurred during treatment with triamterene in a patient with decompensated alcoholic liver cirrhosis and malnutrition. When the triamterene-containing preparation was stopped and folinic acid administered the hematological picture improved, but the patient died, with signs of hepatocellular insufficiency, of gastro-intestinal bleeding. The serum folic-acid level was markedly reduced due to the chronic malnutrition, while the vitamin B12 level was within normal limits. This observation indicates that when the pool of folic-acid coenzymes is reduced, triamterene can cause megaloblastic anemia due to its folic-acid antagonism. Triamterene should, therefore, be given to patients with borderline folic-acid reservoirs, chronic alcoholism or during pregnancy, only under careful serial control of the blood picture.

/CASE REPORTS/ Medications can cause a tubulointerstitial insult leading to acute kidney injury through multiple mechanisms. Acute tubular injury, a dose-dependent process, occurs due to direct toxicity on tubular cells. Acute interstitial nephritis characterized by interstitial inflammation and tubulitis develops from drugs that incite an allergic reaction. Other less common mechanisms include osmotic nephrosis and crystalline nephropathy. The latter complication is rare but has been associated with several drugs, such as sulfadiazine, indinavir, methotrexate, and ciprofloxacin. Triamterene crystalline nephropathy has been reported only rarely, and its histologic characteristics are not well characterized. We report 2 cases of triamterene crystalline nephropathy, one of which initially was misdiagnosed as 2,8-dihydroxyadenine crystalline nephropathy.

/CASE REPORTS/ Acute intravascular hemolysis and renal failure developed while a patient was taking triamterene. A direct antiglobulin test with a polyvalent reagent was positive. Serum caused agglutination of normal red cells in the presence of triamterene and caused an increase of partial hemolysis of both trypsin-treated erythrocytes and red cells from a patient with paroxysmal nocturnal hemoglobinuria (PNH) in the presence of complement. From the results of antibody-neutralization test and treatment with 2-mercaptoethanol, the presence of IgM antibody with lambda light chain could be demonstrated. The triamterene seemed to bind strongly to the red cells in vitro but in vivo there was no detectable adsorption to red cells. Haptenic inhibition was not demonstrated. From these results, it was assumed that this antibody was found to cross-react with methotrexate which has a structure similar to that of triamterene.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including triamterene, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Diuretics; Epithelial Sodium Channel Blockers

MEDICATION (VET)

MEDICATION

Use (kg; approx.) in Germany (2009): >7500

5-Nitroso-2,4,6-triaminopyrimidine is refluxed with phenylacetonitrile in the presence of sodium methoxide.

By condensation of 2,4,6-triamino-5-nitrosopyrimidine with benzyl cyanide.

Preparation ... Weinstock, Wiebelhaus, United States of America patent 3081230 (1963 to SK&f)

Table: Triamterene Preparations [Table#4575]

Table: Triamterene and Hydrochlorothiazide (Co-triamterzide) Preparations [Table#4576]