Tham

Pregnancy Category: C

Lactation: not known if present in breast milk, use caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.100

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100

• Importance of informing patients of other important precautionary information.100 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Check your blood sugar as you have been told by your doctor.
• If you are 65 or older, use Tham with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Trouble breathing, slow breathing, or shallow breathing.
• Low blood sugar. Signs include anger, shaking, fast heartbeat, confusion, or sweating. Keep hard candies, liquid glucose, or orange juice on hand for low blood sugar.
• This medicine may cause tissue damage if the drug leaks from the vein. Tell your nurse if you have any redness, burning, pain, swelling, blisters, skin sores, or leaking of fluid where the drug is going into your body.

Tham Solution (tromeThamine injection) is contraindicated in uremia and anuria. In neonates it is also contraindicated in chronic respiratory acidosis and salicylate intoxication.

Generally, side effects have been infrequent.

Respiratory: Although the incidence of ventilatory depression is low, it is important to keep in mind that such depression may occur. Respiratory depression may be more likely to occur in patients who have chronic hypoventilation or those who have been treated with drugs which depress respiration. In patients with associated respiratory acidosis, tromeThamine should be administered with mechanical assistance to ventilation.

Vascular: Extreme care should be taken to avoid perivascular infiltration. Local tissue damage and subsequent sloughing may occur if extravasation occurs. Chemical phlebitis and venospasm also have been reported.

Hematologic: Transient depression of blood glucose may occur.

Hepatic: Infusion via low-lying umbilical venous catheters has been associated with hepatocellular necrosis.

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection extravasation and hypervolemia.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

Too rapid administration and/or excessive amounts of tromeThamine may cause alkalosis, hypoglycemia, overhydration or solute overload. In the event of overdosage, discontinue the infusion, evaluate the patient and institute appropriate countermeasures. See WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.

The LD50 values for the acute intravenous toxicity of Tham are influenced by the rate of infusion of the dose administered.

Intravenous LD50 Mice = 3500 mg/kg

Intravenous LD50 Rats = 2300 mg/kg

Tham Solution (tromeThamine injection) is administered by slow intravenous infusion, by addition to pump-oxygenator ACD blood or other priming fluid or by injection into the ventricular cavity during cardiac arrest. For infusion by peripheral vein, a large needle should be used in the largest antecubital vein or an indwelling catheter placed in a large vein of an elevated limb to minimize chemical irritation of the alkaline solution during infusion. Catheters are recommended.

Dosage and rate of administration should be carefully supervised to avoid overtreatment (alkalosis). Pretreatment and subsequent determinations of blood values (e.g. pH, PCO2, PO2, glucose and electrolytes) and urinary output should be made as necessary to monitor dosage and progress of treatment. In general, dosage should be limited to an amount sufficient to increase blood pH to normal limits (7.35 to 7.45) and to correct acid-base derangements. The total quantity to be administered during the period of illness will depend upon the severity and progression of the acidosis. The possibility of some retention of tromeThamine, especially in patients with impaired renal function, should be kept in mind.

The intravenous dosage of Tham Solution (tromeThamine injection) may be estimated from the buffer base deficit of the extracellular fluid in mEq/liter determined by means of the Siggaard-Andersen nomogram. The following formula is intended as a general guide:

Tham Solution (mL of 0.3 M) Required =

Body Weight (kg) X

Base Deficit (mEq/liter) X 1.1*

Thus, a 70 kg patient with a buffer base deficit (“negative base excess”) of 5 mEq/liter would require 70 x 5 x 1.1 = 385 mL of Tham Solution containing 13.9 g (115 mEq) of tromeThamine. The need for administration of additional Tham Solution is determined by serial determinations of the existing base deficit.

* Factor of 1.1 accounts for an approximate reduction of 10% in buffering capacity due to the presence of sufficient acetic acid to lower pH of the 0.3 M solution to approximately 8.6.

Correction of Metabolic Acidosis Associated with Cardiac Bypass Surgery: An adverse dose of approximately 9.0 mL/kg (324 mg/kg) has been used in clinical studies with Tham Solution (tromeThamine injection). This is equivalent to a total dose of 630 mL (189 mEq) for 70 kg patient. A total single dose of 500 mL (150 mEq) is considered adequate for most adults. Larger single doses (up to 1000 mL) may be required in unusually severe cases.

It is recommended that individual doses should not exceed 500 mg/kg (227 mg/lb) over a period of not less than one hour. Thus, for a 70 kg (154 pound) patient the dose should not exceed a maximum of 35 g per hour (1078 mL of a 0.3 M solution). Repeated determinations of pH and other clinical observations should be used as a guide to the need for repeat doses.

Correction of Acidity of ACD Blood in Cardiac Bypass Surgery: The pH of stored blood ranges from 6.80 to 6.22 depending upon the duration of storage. The amount of Tham 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. Clinical experience indicates that 2 g (62 mL of a 0.3 M solution) added to 500 mL of ACD blood is usually adequate.

Correction of Metabolic Acidosis Associated with Cardiac Arrest: In the treatment of cardiac arrest, Tham Solution should be given at the same time that other standard resuscitative measures, including manual systole, are being applied. If the chest is open, Tham Solution is injected directly into the ventricular cavity. From 2 to 6 g (62 to 185 mL of a 0.3 M solution) should be injected immediately. Do not inject into the cardiac muscle.

If the chest is not open, from 3.6 to 10.8 g (111 to 333 mL of a 0.3 M solution) should be injected immediately into a larger peripheral vein. Additional amounts may be required to control acidosis persisting after cardiac arrest is reversed.

Correction of Metabolic Acidosis Associated with RDS in Neonates and Infants: The initial dose of Tham Solution should be based on initial pH and birthweight amounting to approximately 1 mL per kg for each pH unit below 7.4. Further doses have been given according to changes in PaO2, pH and PCO2.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See CONTRAINDICATIONS.

Caution is recommended. Excreted into human milk: Unknown Excreted into animal milk: Data not available The effects in the nursing infant are unknown.

Tham Solution (tromethamine injection) is a sterile, non-pyrogenic 0.3 M solution of tromethamine, adjusted to a pH of approximately 8.6 with glacial acetic acid. It is administered by intravenous injection, by addition to ACD blood for priming cardiac bypass equipment and by injection into the ventricular cavity during cardiac arrest.

Each 100 mL contains tromethamine 3.6 g (30 mEq) in water for injection. The solution is hypertonic 389 mOsmol/L (calc.). pH 8.6 (8.4-8.7).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except acetic acid for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded.

Tham solution is a parenteral systemic alkalizer and fluid replenisher.

Tromethamine, USP (sometimes called “tris” or “tris buffer”) is chemically designated 2-amino-2-(hydroxymethyl)-1, 3- propanediol, a solid readily soluble in water, also classified as an organic amine buffer. It has the following structural formula:

Water for Injection, USP is chemically designated H 0.

Tham Solution (tromethamine injection) is supplied in a single-dose 500 mL large volume glass container (List No. 1593).

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Protect from freezing.

Hospira, Inc., Lake Forest, IL 60045 USA, Revised: Jan 2018