Tromethamine is a parenteral, highly alkaline, sodium-free solution used for short-term treatment of metabolic acidosis. It is used for the prevention and correction of systemic metabolic acidosis associated with cardiac bypass surgery, acidity from acid citrate dextrose, and cardiac arrest. Sodium bicarbonate is usually preferred in the treatment of metabolic acidosis. Tromethamine is hypertonic and can usually only be used for a short period of time without risking solute and fluid overload. In neonates and infants with respiratory failure, tromethamine has been used as an alternative to bicarbonate to treat severe cases of metabolic acidosis with concurrent respiratory acidosis because it does not raise PCO2. Tromethamine has also been used in neonates and infants with hypernatremia and metabolic acidosis to avoid the additional sodium associated with sodium bicarbonate administration. Tromethamine (Tham) was approved by the FDA in 1971.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Tromethamine is administered by slow intravenous infusion, by addition to ACD blood for priming cardiac bypass equipment, and by direct injection into the ventricular cavity during cardiac arrest.
-Blood pH, PCO2, serum bicarbonate, serum glucose, and serum electrolyte concentrations should be measured before, during, and after tromethamine therapy.
Route-Specific Administration
Injectable Administration
Intravenous Administration
-Available as a 0.3 M solution.
-Administer intravenously over at least 1 hour.
-If infusing via peripheral vein, use a large needle in the largest antecubital vein or place an indwelling catheter in a large vein of an elevated limb to minimize irritation during infusion. Catheters are recommended.
-Prior to administration, and frequently thereafter, blood values (e.g., pH, PCO2, PO2, glucose, and electrolytes) and urinary output should be evaluated.
-Dosage should be individualized based on severity and progression of acidosis and should be carefully monitored to avoid alkalosis. Dosage should be limited to the amount needed to increase blood pH to normal and to correct acid-base imbalances.
Other Injectable Administration
Intraventricular Administration
-During cardiac arrest, tromethamine should be administered at the same time that other standard resuscitative measures are being applied, including manual systole.
-If the chest is open, tromethamine may be administered into the intraventricular cavity.
-Do not inject into the cardiac muscle.
In general, adverse reactions with tromethamine therapy are rare.
Although data are lacking in humans, increases in coagulation time have been seen in animal studies of tromethamine.
Respiratory depression may occur with high dose tromethamine due to increased blood pH and decreased CO2 concentration. This reaction is more likely to occur in patients who have chronic hypoventilation or in those who have been treated with drugs that depress ventilation. The dosage should be adjusted to ensure blood pH does not rise above normal. In patients with concomitant respiratory acidosis and metabolic acidosis, tromethamine should be administered with mechanical ventilation.
Extravasation may occur with tromethamine treatment. Extreme care should be used when administering tromethamine injection to avoid perivascular infiltration which may result in inflammation, local tissue damage, sloughing and necrosis. The risk of intravenous thrombosis and venospasm may be reduced by ensuring that the injection needle is placed well inside the largest vein and that the solution is administered slowly. Other reactions which may occur due to technique of administration or because of the high osmolar load of the solution include chemical phlebitis extending from the site of injection extravasation, fever, and infection at the site of injection. If an adverse reaction develops during tromethamine therapy, discontinue the infusion, evaluate the patient and initiate appropriate medical therapy.
Transient, prolonged (up to several hours) hypoglycemia may occur with tromethamine therapy. To reduce the risk of hypoglycemia, avoid rapid administration and use the lowest dose needed for the shortest duration of time to correct the existing acidosis. Frequent blood glucose concentrations should be monitored during and after tromethamine administration.
Hepatic necrosis has been reported with the infusion of tromethamine via low-lying umbilical venous catheters.
The use of tromethamine injection can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congestion, and pulmonary edema.
Tromethamine is contraindicated for use in patients with uremia and/or anuria (anuric renal failure). Tromethamine is excreted by the kidneys and should be used cautiously in patients with renal disease, renal impairment, and in patients with reduced urinary output due to the potential for hyperkalemia and the possibility of decreased excretion and retention of tromethamine. If tromethamine is used in patients with renal insufficiency, ECG monitoring and frequent serum potassium measurements are recommended.
If extravasation occurs during the administration of tromethamine, inflammation, necrosis, and skin sloughing may occur (see Adverse Reactions). Administer tromethamine cautiously to avoid perivascular infiltration.
Respiratory depression may occur with high dose tromethamine due to increased blood pH and decreased CO2 concentration. In patients with concomitant respiratory acidosis with metabolic acidosis, tromethamine should be administered with mechanical ventilation. In addition, tromethamine is contraindicated in newborns with chronic respiratory acidosis.
Clinical studies of tromethamine did not include a sufficient number of geriatric patients (>= 65 years) to determine differences in safety and efficacy compared to younger patients. Other reported clinical experiences have not identified differences in response between the elderly and younger patients; however, there is generally a greater frequency of decreased hepatic, renal (tromethamine is excreted renally), and cardiac function as well as concomitant diseases and drug therapy that should be considered when administering tromethamine to an elderly patient. Dose selection in the elderly should be cautious, usually starting at the low end of the dosing range, and renal function should be monitored. Tromethamine can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations (worsening any existing electrolyte imbalance), overhydration, congested states (e.g., congestive heart failure aggravation) or pulmonary edema in any population, but the elderly may be more at risk.
Tromethamine is contraindicated in neonates with salicylate intoxication and chronic respiratory acidosis. It is also contraindicated in patients with anuria or uremia. Use tromethamine cautiously in children with renal impairment since the drug is primarily excreted by the kidneys and can accumulate leading to increased risk of hyperkalemia or other adverse reactions. Frequent monitoring of serum potassium and ECG monitoring should be used in pediatric patients with renal impairment receiving tromethamine. Per the manufacturer, the safety and efficacy of tromethamine in pediatric patients is based on over 30 years of clinical experience that has been documented in the literature and through safety surveillance. Tromethamine is used to treat severe metabolic acidosis with concomitant respiratory acidosis in infants and neonates with respiratory failure because, unlike bicarbonate, tromethamine does not increase PCO2. It is also used preferentially over bicarbonate in infants and neonates with hypernatremia and metabolic acidosis to avoid the additional sodium seen with bicarbonate administration. For acidotic neonates and infants with respiratory distress syndrome (RDS), bicarbonate is the treatment of choice due to the osmotic effects of tromethamine and large continuous doses typically needed required. If tromethamine is used in full-term neonates and premature neonates, hypoglycemia may occur (see Adverse Effects).
Use tromethamine during pregnancy only if clearly needed. It is not known whether tromethamine can cause fetal harm or if it adversely affects reproduction capacity. Animal reproductive studies have not been conducted with tromethamine.
Use tromethamine with caution if given to a breast-feeding mother. It is not known whether tromethamine is excreted in human milk.
Tromethamine may cause hypoglycemia. Overdosage and rapid administration may cause prolonged hypoglycemia; infuse slowly and in amounts sufficient only to correct acidosis. Avoid overcorrection. Monitor blood glucose during and after therapy in all patients; frequent monitoring may be necessary for patients at high risk of hypoglycemia.
General dosing information
-Monitor blood pH, PCO2, serum bicarbonate, serum glucose, serum electrolyte concentrations, and urinary output before, during, and after tromethamine therapy.
-Because of the risk for hypoglycemia, some experts recommend the coadministration of a dextrose-containing solution for neonates receiving tromethamine.
-Clinical experience with tromethamine has been limited to short-term use; therefore, tromethamine should not be administered for more than 24 hours except in life-threatening situations.
For the prevention and correction of metabolic acidosis:
-for the treatment of metabolic acidosis associated with cardiopulmonary bypass surgery:
Intravenous dosage:
Adults: 9 mL/kg (324 mg/kg) IV. A single dose of 500 mL is considered adequate for most adults. Doses up to 1000 mL may be necessary for cases of severe metabolic acidosis. Individual doses should not exceed 500 mg/kg over a period of not less than 1 hour (e.g., for a 70 kg patient, the dose should not exceed 35 g/hr [1078 mL of a 0.3 M solution]). Careful monitoring of pH and other clinical observations should be used as a guide to determine the need for subsequent doses.
Children and Adolescents: The dosage should be based on the clinical judgement of the clinician. A dose of 9 mL/kg (324 mg/kg) IV has been used in clinical studies. A single dose of 500 mL is considered adequate for most adults; however, doses up to 1000 mL have been used for cases of severe metabolic acidosis. Individual doses should not exceed 500 mg/kg over a period of not less than 1 hour (e.g., for a 70 kg patient, the dose should not exceed 35 g/hr [1078 mL of a 0.3 M solution]). Careful monitoring of pH and other clinical observations should be used as a guide to determine the need for subsequent doses.
-for the correction of acidity of ACD blood during cardiopulmonary bypass surgery:
Extracorporeal dosage:
Adults, Adolescents, and Children: Clinical experience indicates that 62 mL (2 g) added to 500 ml of ACD blood is usually sufficient to correct the acidity of ACD blood used for priming the pump-oxygenator. The pH of stored blood ranges from 6.22 to 6.80 depending upon the duration of storage. The amount of tromethamine solution used to correct this acidity ranges from 0.5 to 2.5 g (15 to 77 mL of a 0.3 M solution) added to each 500 mL of ACD blood used for priming the pump-oxygenator.
-for the treatment of severe metabolic acidosis:
Intravenous dosage:
Adults, Adolescents, and Children: Used as an alternative to sodium bicarbonate in select patients. Dose depends on weight and buffer base deficit. When the deficit is known, the manufacturer recommends the following formula: Dose (mL) of 0.3 M tromethamine solution = body weight (kg) x base deficit (mEq/L) x 1.1. Carefully monitor blood pH, PCO2, PO2, blood glucose, electrolytes, and renal function to determine the need for subsequent doses. Generally limit the dosage to an amount sufficient to return blood pH to normal range (7.35 to 7.45) and correct acid-base derangement. Although a maximum dosage for children and adolescents has not been clearly defined, the dosage is generally limited to 15 mmol/kg/24 hours in adults.
Infants and Neonates: For metabolic acidosis associated with respiratory distress syndrome, the initial dosage should be approximately 1 mL/kg IV for each pH unit below 7.4. Administer further dosages based on clinical condition and changes in PaO2, pH, and PCO2. Alternatively, some experts recommend calculating the dose of tromethamine using the following formula: Dose (mL) of 0.3 M tromethamine solution = body weight (kg) x base deficit (mEq/L). A maximum daily dose of 5 to 7 mmol/kg has been recommended for neonates with normal renal function to prevent accumulation.
-for the correction of metabolic acidosis associated with cardiac arrest:
Intraventricular dosage:
Adults: If the chest is open, 62 to 185 mL (2 to 6 g) of a 0.3 M solution injected directly into the ventricular cavity. Do not inject into the cardiac muscle.
Intravenous dosage:
Adults: If the chest is not open, 111 to 333 mL (3.6 to 10.8 g) of a 0.3 M solution IV immediately into a larger peripheral vein. Additional tromethamine may be necessary to treat acidosis persisting after cardiac arrest.
Maximum Dosage Limits:
NOTE: Because clinical experience has been limited generally to short-term use of tromethamine, the drug should not be administered for more than a period of 1 day except in a life-threatening situation.
-Adults
500 mg/kg IV per any single dose to treat metabolic acidosis; repeat doses are guided by clinical response and determination of acid-base status.
-Geriatric
500 mg/kg IV per any single dose to treat metabolic acidosis; repeat doses are guided by clinical response and determination of acid-base status.
-Adolescents
Dosage is dependent on clinical response and acid-base status.
-Children
Dosage is dependent on clinical response and acid-base status.
-Infants
Dosage is dependent on clinical response and acid-base status. Some experts have recommended a maximum dose of 7 mmol/kg/day IV for the treatment of respiratory distress syndrome in infants.
-Neonates
Dosage is dependent on clinical response and acid-base status. Some experts have recommended a maximum dose of 7 mmol/kg/day IV for the treatment of respiratory distress syndrome in neonates.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; use caution as elimination of the drug is likely decreased. Do not use in uremic or anuric patients (see Contraindications).
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Acetaminophen; Aspirin: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acrivastine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Amphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Amphetamine; Dextroamphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Amphetamines: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Aspirin, ASA: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Dipyridamole: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Omeprazole: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Oxycodone: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Benzphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Bismuth Subsalicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Brompheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Cetirizine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Choline Salicylate; Magnesium Salicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Codeine; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Desloratadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dexbrompheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dextroamphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dextromethorphan; Quinidine: (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
Donepezil; Memantine: (Moderate) Urinary alkalinizing agents may decrease the elimination of memantine, resulting in drug accumulation and potential toxicity. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Memantine should be used with caution with drugs known to increase urinary pH.
Fexofenadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Flecainide: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Ibuprofen; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Lisdexamfetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Lithium: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with lithium, especially patients who are stabilized on lithium, as urinary alkalinization increases the renal clearance of lithium. If coadministration can not be avoided, monitor lithium serum concentrations and patient clinical response very closely. Also of note, lithium clearance is increased if hypernatremia occurs.
Loratadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Magnesium Salicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Memantine: (Moderate) Urinary alkalinizing agents may decrease the elimination of memantine, resulting in drug accumulation and potential toxicity. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Memantine should be used with caution with drugs known to increase urinary pH.
Methamphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Methenamine: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Methenamine; Sodium Salicylate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Naproxen; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Pseudoephedrine; Triprolidine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Quinidine: (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
Salsalate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Tromethamine prevents or corrects acidosis by binding hydrogen ions (H+). It binds cations of fixed or metabolic acids and also hydrogen ions of carbonic acid, resulting in an increase in bicarbonate anion (HCO3-). A significant portion (30% at pH 7.4) of tromethamine is not ionized and is capable of reaching equilibrium in total body water. This nonionized portion may penetrate cells and neutralize acidic ions in the intracellular fluid. Tromethamine also acts as an osmotic diuretic, increasing urine flow, urinary pH, and excretion of fixed acids, carbon dioxide, and electrolytes.
Tromethamine is administered intravenously, by injection into the ventricular cavity during cardiac arrest, and by addition to ACD blood or other priming fluids during cardiac bypass surgery. Tromethamine distributes slowly into cells and intracellular uptake is increased at a more alkaline pH, when more tromethamine is unprotonated. The beta-elimination half-life is 5.6 hours. Tromethamine is rapidly eliminated by the kidney. Eight hours after administration, 75% or more of the tromethamine dose appears in the urine. Urinary excretion continues over 3 days. Renal elimination is mostly by glomerular filtration.
-Special Populations
Renal Impairment
No specific pharmacokinetic data are available. Tromethamine is substantially excreted by the kidneys; renal impairment may decrease elimination of the drug and increase the risk of toxic reactions. The drug is not to be used if uremia or anuria are present.
Pediatrics
No specific pediatric pharmacokinetic data are available; tromethamine has been used in neonates and infants for several decades, and tromethamine is excreted extensively by the kidneys.
Geriatric
No specific pharmacokinetic data are available; the drug is substantially eliminated by the kidney and in general, the potential for the elderly to have decreased renal function may impact drug elimination.