Professional Information
Aminosalicylate Sodium (Systemic)
VA CLASSIFICATION
{01}Primary: AM500
Note: Aminosalicylate sodium, a 4-amino antimycobacterial compound, differs from 5-aminosalicylic acid (mesalamine), which is used in the treatment of nonbacterial inflammatory conditions such as ulcerative colitis, proctosigmoiditis, or proctitis.
Commonly used brand name(s): Nemasol Sodium; Tubasal.
Another commonly used name is
PAS .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Antibacterial (antimycobacterial)—
Indications
Accepted
Tuberculosis (treatment)—Aminosalicylate sodium is indicated in the treatment of pulmonary and extrapulmonary tuberculosis caused by Mycobacterium tuberculosis. {07} However, aminosalicylate sodium is much less effective than other antituberculars and must be given in combination with other medications. {10}
—Since bacterial resistance may develop rapidly when aminosalicylate sodium is administered alone, it should only be administered concurrently with other antimycobacterials. Development of resistance to streptomycin and isoniazid may be delayed when these medicines are administered concurrently with aminosalicylate sodium. {21}
Unaccepted
Aminosalicylate sodium has been used in the treatment of atypical mycobacterial infections; however, most atypical mycobacteria are not inhibited by this medication. {10}
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
211.15
Mechanism of action/Effect:
Bacteriostatic; analog of aminobenzoic acid (PABA) {10}; believed to suppress growth and reproduction of Mycobacterium tuberculosis by competitively inhibiting folic acid formation. {07}
Absorption:
Rapidly and well absorbed from gastrointestinal tract. {08} {10}
Distribution:
Diffuses readily into various body fluids, achieving high concentrations in pleural fluid, but low concentrations in the cerebrospinal fluid (CSF) {10} ; diffuses readily into kidneys, lungs, and liver, achieving high concentrations in caseous tissue.
Protein binding:
Low (15%). {02}
Biotransformation:
Hepatic; greater than 50% acetylation to inactive metabolites. {07}
Half-life:
Normal renal function—:
45 to 60 minutes. {10}
Impaired renal function—:
Up to 23 hours.
Time to peak serum concentration
1 to 2 hours {08}.
Peak serum concentration
Approximately 75 mcg per mL after a 4 gram oral dose. {02}
Elimination:
Renal; 85% of a dose is rapidly excreted within 7 to 10 hours by glomerular filtration and tubular secretion: {10} {11} {19} 14 to 33% excreted unchanged in the urine {07} {19}, 50% as metabolites. {10}
In dialysis——
It is not known if aminosalicylate sodium is removed by dialysis. {02}
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to other salicylates, including methyl salicylate (oil of wintergreen), or to other compounds containing a p-amino phenyl group (certain sulfonamides and dyes) may be sensitive to this medication also.
Pregnancy/Reproduction
Pregnancy—
Adequate and well-controlled studies in humans have not been done. In one study, an increased malformation rate for ears and limbs, and hypospadias were reported in infants of patients taking aminosalicylates with other antitubercular medications. {20} However, other studies have not found aminosalicylates to be teratogenic. {13}
Breast-feeding
Aminosalicylate sodium is distributed into breast milk. However, problems in humans have not been documented. {13}
Pediatrics
No information is available on the relationship of age to the effects of aminosalicylate sodium in pediatric patients.
Geriatrics
No information is available on the relationship of age to the effects of aminosalicylate sodium in geriatric patients.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
» Aminobenzoates{18} (aminobenzoates may be absorbed by bacteria preferentially over aminosalicylate sodium, thereby antagonizing the bacteriostatic effect of aminosalicylate sodium; concurrent use is not recommended)
Anticoagulants, coumarin- or indandione-derivative{17} (when coumarin- or indandione-derivative anticoagulants are used concurrently with aminosalicylate sodium, their effects may be increased because of decreased hepatic synthesis of procoagulant factors; dosage adjustments may be necessary during and after aminosalicylate sodium therapy)
Probenecid or{07}{10}
Sulfinpyrazone (may decrease renal tubular secretion of aminosalicylate sodium when used concurrently, resulting in increased and prolonged serum concentrations and/or toxicity; aminosalicylate sodium dosage adjustments may be necessary during and after concurrent therapy, and patients should be monitored; however, probenecid is not currently recommended as an adjunct to therapy with aminosalicylate sodium)
Rifampin{10}{15} (aminosalicylate sodium may impair absorption of rifampin, resulting in decreased rifampin serum concentrations; patients should be advised to take aminosalicylate sodium and rifampin at least 6 hours apart)
Vitamin B 12{12}{16} (aminosalicylate sodium may impair absorption of vitamin B 12 from the gastrointestinal tract; requirements for vitamin B 12 may be increased in patients receiving aminosalicylate sodium)
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With diagnostic test result
Glucose, urine{21} (aminosalicylate sodium may produce a false-positive test result with copper sulfate tests)
Schilling test{03} (aminosalicylate sodium may impair absorption of vitamin B 12 from the gastrointestinal tract; study results may be misinterpreted as pernicious anemia or other causes of malabsorption)
Urobilinogen, urine (aminosalicylate sodium reacts with Ehrlich's reagent, producing an orange turbidity and/or yellow color; some commercially available reagent strips that use a similar reagent system are also affected)
With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Aspartate aminotransferase (AST [SGOT]) (values may be increased {07} {08})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Except under special circumstances, this medication should not be used when the following medical problem exists:
» Previous allergic reaction to aminosalicylates, other salicylates or sulfonamides
Risk-benefit should be considered when the following medical problems exist
» Congestive heart failure{08} (high sodium concentrations may exacerbate condition because of fluid accumulation and overload)
» Gastric ulcer{08}{10} (aminosalicylate sodium commonly causes gastric irritation)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency{21} (aminosalicylate sodium may cause hemolytic anemia in G6PD-deficient patients)
Hepatic function impairment, severe{07} (aminosalicylate sodium may cause hepatitis)
Renal function impairment, severe{21} (patients with impaired renal function may require a reduction in dose or withdrawal of the medication)
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent {07} {09} {10}
Hypersensitivity reaction (eosinophilia; fever; joint pains; leukopenia; skin rash or itching; unusual tiredness or weakness)
Incidence less frequent {25}
Crystalluria (lower back pain; pain or burning while urinating)
goiter or myxedema —with prolonged high-dose therapy (changes in menstrual periods; decreased sexual ability in males; dry, puffy skin; swelling of front part of neck; unusual weight gain){13}{14}
hemolytic anemia (abdominal pain; backache; paleness of skin)—with G6PD deficiency{19}
hepatitis or jaundice (yellow eyes or skin)
infectious mononucleosis–like syndrome (fever; headache; skin rash; sore throat; unusual tiredness or weakness)
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent {10}
Gastrointestinal disturbances (abdominal pain; anorexia; diarrhea; nausea; vomiting)
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Aminosalicylate Sodium (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Allergies to aminosalicylates, other salicylates, or sulfonamides
Pregnancy—An increased malformation rate for ears and limbs and hypospadias were reported in patients taking aminosalicylates with other antitubercular medications; however, other studies did not find aminosalicylates to be teratogenic
Breast-feeding—Aminosalicylate sodium is distributed into breast milk
Other medications, especially aminobenzoates
Other medical problems, especially the presence of congestive heart failure or a gastric ulcer
Proper use of this medication
Taking with or after meals or with antacid to minimize possible gastric irritation {10}
» Compliance with full course of therapy, which may take months or years
» Importance of not missing doses and taking at evenly spaced times
» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses
» Proper storage
Precautions while using this medication
Checking with physician if no improvement within 2 or 3 weeks
Not taking aminosalicylate sodium within 6 hours of rifampin
» Diabetics: False-positive reactions with copper sulfate urine glucose tests may occur
Side/adverse effects
Signs of potential side effects, especially hypersensitivity reactions, crystalluria, goiter, myxedema, hemolytic anemia, hepatitis or jaundice, and infectious mononucleosis–like syndrome
General Dosing Information
Aminosalicylate sodium may be taken with or after meals or with an antacid if gastric irritation occurs. If gastric irritation persists, a temporary reduction in dose or a brief rest period of up to 2 weeks may be helpful. Aminosalicylate sodium may then be restarted in small daily doses and gradually increased to full therapeutic doses. If tolerated, the total daily dose may be given as a single dose. {21}
If crystalluria occurs, the urine should be maintained at neutral or alkaline pH. {21}
Therapy may have to be continued for 1 to 2 years, and may even be required for up to several years or indefinitely, although in some patients shorter treatment regimens may be effective.
Patient compliance may be poor because of gastric irritation or hypersensitivity reactions. Children may tolerate aminosalicylate sodium better than do adults.
Oral Dosage Forms
AMINOSALICYLATE SODIUM TABLETS USP
Usual adult and adolescent dose
Tuberculosis
In combination with other antimycobacterials: Oral, 3.3 to 4 grams (aminosalicylic acid) every eight hours; or 5 to 6 grams every twelve hours. {08} {12}
Usual adult prescribing limits
Up to 20 grams (aminosalicylic acid) daily.
Usual pediatric dose
Tuberculosis
In combination with other antimycobacterials: Oral, 50 to 75 mg (aminosalicylic acid) per kg of body weight every six hours; or 66.7 to 100 mg per kg of body weight every eight hours. {11}
Note: The maximum daily dose in children should not exceed 12 grams (aminosalicylic acid). {22}
Strength(s) usually available
U.S.—
500 mg (equivalent to 365 mg of aminosalicylic acid) (Rx) [Tubasal (sodium 2.4 mEq){23}{24}]
Canada—
500 mg (equivalent to 365 mg of aminosalicylic acid) (Rx) [Nemasol Sodium (sodium 2.4 mEq){06}]
Packaging and storage:
Store below 40 °C (104 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.
Stability:
Aminosalicylates deteriorate rapidly in contact with water, heat, or sunlight.
Auxiliary labeling:
• Continue medicine for full time of treatment.
• Keep from heat and light.
Revised: 05/02/1994
References
- USP DI 1989, VA Medication Classification System: 2472.
- Holdiness MR. Clinical pharmacokinetics of the antituberculosis drugs. Clin Pharmacokinet 1984; 9(6): 511-44.
- Hladik WB, Saha GB, Study KT, editors. Essentials of nuclear medicine science. Baltimore: Williams & Wilkins, 1987: 209-10.
- Teebacin (Palisades). Red book 1989. Montvale, NJ: Medical Economics Data, 1989: 666.
- Aminosalicylate sodium (generic). Red book 1989. Montvale, NJ: Medical Economics Data, 1989: 141.
- Nemasol Sodium(ICN). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 24th ed. Ottawa: Canadian Pharmaceutical Association, 1988: 595.
- Reed MD, Blumer JL. Clinical pharmacology of antitubercular drugs. Pediatr Clin N Am 1983; 30(1): 177-87.
- Sadik F. Tuberculosis. Pharmindex 1985: 11-6.
- Driscoll DF, Brandstetter RD, Walczyk M. Pulmonary TB: etiology and treatment. US Pharmacist 1982: 39-57.
- Gilman AG, Goodman LS, Rall TW, Murad F, editors. Goodman and Gilman's the pharmocological basis of therapeutics. 7th ed. New York: Macmillan, 1985: 1208-9.
- AMA Drug evaluations. 6th ed. Chicago: American Medical Association, September 1986: 1538.
- AMA Drug evaluations. 6th ed. Chicago: American Medical Association, September 1986: 596.
- Berkowitz RL, Coustan DR, Mochizuki TK. Handbook for prescribing medications during pregnancy. 2nd ed. Boston: Little, Brown and Company, 1986: 15.
- Melmon KL, Morrelli HF, Hoffman BB, Nierenberg DW, editors. Melmon and Morrelli's clinical pharmacology. Basic principles in therapeutics. 2nd ed. New York: McGraw-Hill, Inc., 1978: 772.
- Tatro DS, editor. Drug interaction facts. St Louis: Facts and Comparisons, 1983: 423.
- Tatro DS, editor. Drug interaction facts. St Louis: Facts and Comparisons, 1983: 531.
- Stockley I. Drug interactions. Boston: Blackwell Scientific Publishers, 1981: 120.
- Hansten PD, Horn JR. Drug interactions. 5th ed. Philadelphia: Lea & Febiger, 1985: 201.
- Kucers A, Bennett NM, editors. The use of antibiotics. 3rd ed. New York: Lippincott, 1979: 825-31.
- Briggs GG, Freeman RK, Yaffe SJ. A reference guide to fetal and neonatal risk. Drugs in pregnancy and lactation. 2nd ed. Baltimore: Williams & Wilkins, 1986: 14.
- McEvoy GK, editor. AHFS Drug information 89. Bethesda, MD: American Society of Hospital Pharmacists, 1989: 358.
- Benitz WE, Tatro DS. The pediatric drug handbook. 2nd ed. Chicago: Year Book Medical Publishers, Inc., 1988: 615.
- Panel comment, 5/23/89.
- Personal communication, CMC-Consolidated Midland Corporation, 5/31/89.
- Gilman AG, Goodman LS, Rall TW, Murad F, editors. Goodman and Gilman's the pharmocological basis of therapeutics. 5th ed. New York: Macmillan, 1975: 1202-4.
| Link to this page |  |
Printable Version |  |
Email Page |
