General Monograph, CPhA
Pharmacology: Para-aminosalicylate sodium is the sodium salt of para-aminosalicylic acid (PAS).
Note: Aminosalicylate sodium differs from 5-aminosalicylic acid (5-ASA), which is used for the treatment of inflammatory bowel disease.
PAS sodium is a highly specific bacteriostatic agent active only against M. tuberculosis. PAS sodium competitively inhibits the formation of dihydrofolic acid from aminobenzoic acid, thus preventing bacterial synthesis of folic acid required for further growth.
Pharmacokinetics: PAS sodium is readily absorbed from the gastrointestinal tract. Following oral administration of a 4 g dose, peak serum concentration is attained within 0.5 to 1 hour.
The drug is distributed into most tissues and fluids and reaches high concentrations in the lungs, kidneys and liver; however, it does not appear in cerebrospinal fluid in significant amounts except in patients with inflamed meninges, where CSF concentrations are reported to be 10 to 50% of plasma concentration. PAS is 50 to 70% plasma protein bound and has a half-life of about 1 hour. Over 80% is excreted by the kidney in approximately 10 hours with more than 50% in the acetylated form. Excretion is reduced in patients with impaired renal function.
Indications: For use with other antituberculosis agents in the second-line treatment of tuberculosis when caused by susceptible strains of M. tuberculosis.
Contraindications: Severe hypersensitivity to PAS sodium and its congeners.
Precautions: PAS sodium frequently causes gastrointestinal symptoms such as nausea, vomiting, abdominal pain, diarrhea and anorexia. Rarely, peptic ulcer and gastric hemorrhage have occurred. Malabsorption of vitamin B12, folic acid, iron and lipids has also occurred. Supplementation should be considered for patients on long-term therapy.
Hypersensitivity reactions may include fever, rash, vaculitis, blood dyscrasias, hepatitis and jaundice. Patients should be advised to discontinue the drug immediately at the first sign of hypersensitivity. The possibility of cross-sensitivity must be considered in patients who have hypersensitivity to structurally-related compounds such as aminosalicylates, sulfonamides or other salicylates.
PAS sodium should be used with caution in patients with renal or hepatic dysfunction or gastric ulcer.
The sodium load associated with PAS sodium tablets (2.4 mmol/500 mg tablet) should be taken into consideration for patients in whom excess sodium is potentially harmful.
Drug Interactions : There is some evidence that PAS sodium may enhance the hypoprothrombinemic response to warfarin. Dosage adjustment of warfarin may be necessary.
Pregnancy: Safe use of PAS sodium during pregnancy has not been established.
Lactation: PAS is excreted in breast milk; however, effect on the nursing infant is unknown.
Adverse Effects: Gastrointestinal (common): nausea, vomiting, diarrhea, abdominal pain, anorexia. Malabsorption has occurred occasionally. Rarely, PAS sodium has caused peptic ulcer and gastrointestinal hemorrhage.
Hypersensitivity: fever, skin eruptions of various types, infectious mononucleosis-like syndrome, vasculitis, encephalopathy.
Hepatic: jaundice, hepatitis.
Hematological: leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (especially in patients with G6PD deficiency), Löffler’s eosinophilia.
Other: albuminuria, crystalluria acidosis and goiter with or without myxedema (with high doses of PAS sodium).
Dosage: PAS sodium must not be used alone for treatment of tuberculosis. Adults: 10 to 12 g orally per day in 2 to 4 divided doses.
Children: 150 to 300 mg/kg/day in 3 or 4 divided doses, not to exceed adult dosage.
Dosage reduction in patients with impaired renal function is recommended.
Gastrointestinal disturbances may be minimized by taking the drug with or after meals or with an antacid.
PAS SODIUM General Monograph, CPhA Aminosalicylate Sodium Antimycobacterial