4-Aminosalicylic acid

153.14

153.14

473071

200-613-5

5B2658E0N2

2083

DTXSID2022591

C47394

MINUTE CRYSTALS FROM ALC|WHITE, OR NEARLY WHITE, BULKY POWDER|NEEDLES, PLATES FROM ALC-ETHER|A reddish-brown crystalline powder is obtained on recrystallization from ethanol-ether.

J04AA01|J - Antiinfectives for systemic use

29225000

83.6

1.3

Colorless Powder

1.5±0.1 g/cm3

150.5 °C (decomp)

347ºC

184.1±25.1 °C

1.691

H2O: 2 g/L (20 ºC)

Store at 0-5°C

Peritoneal-mouse LD50: 4250 mg/kg; oral-mouse LD50: 4000 mg/kg

Flammable; burning produces toxic nitrogen oxide fumes

ODORLESS, OR HAS SLIGHT ACETOUS ODOR

PH (SATURATED AQ SOLN): BETWEEN 3 & 3.7

2.05(at 25 °C)

2.05 (at 25 °C)|PKA: 3.25

PH OF 0.1% AQ SOLN: 3.5|CRYSTALS; DECOMP @ 224 °C /HYDROCHLORIDE/|WHITE TO CREAM-COLORED CRYSTALS OR POWDER; ODORLESS, & HAS ALKALINE, SLIGHTLY BITTER TASTE /CALCIUM SALT/|WHITE TO CREAM-COLORED, CRYSTALLINE POWDER; PRACTICALLY ODORLESS & HAS SALINE TASTE /POTASSIUM SALT/|For more Other Experimental Properties (Complete) data for P-AMINOSALICYLIC ACID (7 total), please visit the HSDB record page.

UN17898/PG3

2

22-36-36/37/38-45-35-61

26-37/39-45-53-36-36/37/39

VO1225000

Xn,Xi,T

Warehouse ventilated, low temperature and dry

AQ SOLN DECOMP SLOWLY & DARKEN IN COLOR /CALCIUM SALT/

P305 + P351 + P338

H319

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

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).

A review of the literature on the clinical experience, tolerance and toxicity of mesalamine (5-aminosalicylic acid), aminosalicylic acid (4-aminosalicylic acid) and newer mesalamine based drugs for the treatment of chronic inflammatory bowel disease is presented.[Jarnerot G; Drugs 37 (Jan): 73-86 (1989)]|The initial therapy and retreatment of pulmonary tuberculosis as well as various complicating factors that may affect treatment decisions are presented. Chemotherapeutic agents used in the treatment of tuberculosis and their dosage regiments are mentioned including isoniazid, ethambutol, rifampin, pyrazinamide, ethionamide, cycloserine, streptomycin, kanamycin, aminosalicylate (aminosalicylic acid), and capreomycin.[Spagnolo SV; Drug Therapy 15 (Nov): 91-92, 97-100 (1985)]

|Warning|H315 (39.06%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 64 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

moderately toxic

LD50=4 gm/kg (orally in mice); LD50=3650 mg/kg (orally in rabbits)

...PARA-AMINOSALICYLIC ACID.../INHIBITS METABOLISM OF CHLORAMPHENICOL/|PENTOBARBITAL /SRP: CNS DEPRESSION/ IN MICE WAS ENHANCED AFTER PRE-TREATMENT WITH... P-AMINOSALICYLIC ACID. INCR /SRP: CNS DEPRESSION/ APPEARED TO BE DUE TO RELEASE OF PENTOBARBITAL FROM SERUM-PROTEIN BINDING, RESULTING IN HIGHER CEREBRAL CONCN...|ADDITIVE & SYNERGISTIC WITH STREPTOMYCINS & ISONIAZID.|Probenecid decreases the renal excretion of this agent.|For more Interactions (Complete) data for P-AMINOSALICYLIC ACID (19 total), please visit the HSDB record page.

50-60%

For the treatment of tuberculosis|Granupas is indicated for use as part of an appropriate combination regimen for multi-drug resistant tuberculosis in adults and paediatric patients from 28 days of age and older when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability (see section 4.4).Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Antitubercular Agents|EXPTL USE: LIPID LOWERING AGENT. 6 G GIVEN FOR 4 WK. IT WAS CONCLUDED THAT IT LOWERS ELEVATED SERUM TRIGLYCERIDE LEVELS AS WELL AS ELEVATED SERUM CHOLESTEROL LEVELS.|USED ALONE, IT CAN SOMETIMES SUCCESSFULLY MANAGE /TUBERCULOSIS/...BUT RESISTANCE EMERGES & ALSO TOXICITY LIMITS THE DOSE. THEREFORE, PAS IS NEARLY ALWAYS USED IN COMBINATION WITH 1 OR 2 OTHER ANTITUBERCULAR DRUGS. ...PAS SUPPORTS THE OTHER DRUGS & DELAYS THE EMERGENCY OF RESISTANCE.|AMINOSALICYLIC ACID...HAS POTENT HYPOLIPIDEMIC ACTION & REDUCES BOTH CHOLESTEROL & TRIGLYCERIDES. HOWEVER IT HAS NOT BEEN WELL TOLERATED BECAUSE OF GI REACTION.|For more Therapeutic Uses (Complete) data for P-AMINOSALICYLIC ACID (15 total), please visit the HSDB record page.

UNDER NO CIRCUMSTANCES USE SOLN IF ITS COLOR IS DARKER THAN THAT OF FRESHLY PREPD SOLN. ... PREPARE SOLN OF CALCIUM, /POTASSIUM, & SODIUM SALTS/ WITHIN 24 HR OF ADMIN.|FOR THE VARIOUS DEFECTS /FOR EXAMPLE, DEFICIENCY IN ERYTHROCYTE GLUCOSE-6-PHOSPHATE DEHYDROGENASE/ THAT SEEM TO BE SPECIFIC TO PARTICULAR RACES, DIFFERENT DRUGS ELICIT HEMOLYSIS. MOST IMPORTANT OF THESE ARE NITROFURANTOIN, AMINOSALICYLIC ACID...|IN PT WITH IMPAIRMENT OF KIDNEY OR OTHER MECHANISMS FOR CONTROLLING PLASMA CONCN, THE DRUG CAN CAUSE HYPERCALCEMIA. IT MAY ALSO CONTRIBUTE TO UROLITHIASIS. /CA SALT/|The most frequent adverse effects of aminosalicylic acid or its salt are GI disturbances including nausea, vomiting, abdominal pain, diarrhea, and anorexia. Rarely, aminosalicylic acid has caused peptic ulcer and gastric hemorrhage. Adverse GI effects may be minimized in some patients by administering the aminosalicylates with meals; however, symptoms may be severe enough to require discontinuation of the drugs. Malabsorption of vitamin B12 folic acid, iron, and lipids has also occurred occasionally in patients receiving aminosalicylic acid or its salt, possibly as the result of increased peristalsis. The manufacturer states that maintenance therapy with vitamin B12 should be considered in patients receiving aminosalicylic acid for longer than 1 month.|For more Drug Warnings (Complete) data for P-AMINOSALICYLIC ACID (12 total), please visit the HSDB record page.

Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.

Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy. (See all compounds classified as Antitubercular Agents.)

BIOAVAILABILITY STUDIES ON P-AMINOSALICYLIC ACID & ITS SALTS IN 12 SUBJECTS. COLORIMETRIC ASSAY INDICATED THAT PEAK BLOOD LEVELS OCCURRED @ 0.5, 0.75, 1.5, & 3 HR FOR SODIUM, POTASSIUM, & CALCIUM SALTS & P-AMINOSALICYLIC ACID, RESPECTIVELY.|URINE EXCRETION DATA SHOWED ABSORPTION TO BE ESSENTIALLY COMPLETE ALTHOUGH RATES OF ABSORPTION DIFFERED.|Aminosalicyclic acid is readily absorbed from the gastrointestinal tract. A single oral dose of 4 g of the free acid produces maximal concentrations in plasma of about 75 ug/ml within 1.5 to 2 hours. The sodium salt is absorbed even more rapidly. The drug appears to be distributed throughout the total body water and reaches high concentrations in pleural fluid and caseous tissue. However, values in CSF are low, perhaps because of active outward transport.|Over 80% of the drug is excreted in the urine; more than 50% is in the form of the acetylated compound. The largest portion of the remainder is made up of the free acid.|For more Absorption, Distribution and Excretion (Complete) data for P-AMINOSALICYLIC ACID (8 total), please visit the HSDB record page.

Hepatic.|ACETYLATION IS MAJOR ROUTE FOR INACTIVATION OF MANY DRUGS SUCH AS ... P-AMINOSALICYLIC ACID... ENZYMES WHICH CATALYSE THESE REACTIONS, ACETYL COENZYME A:N-ACETYLTRANSFERASES (EC2.3.1.5), ARE LOCATED IN LIVER CYTOSOL.|WHEN ADMIN ORALLY TO MAN IT IS RAPIDLY ABSORBED, & IS EXCRETED IN URINE AS UNCHANGED P-AMINOSALICYLIC ACID & AS ACETYL GLUCURONYL, GLYCYL & GLUTAMINYL CONJUGATES.|YIELDS 5-AMINO-2-CARBOXYPHENYL-BETA-D-GLUCURONIDE IN MAN. 4-AMINOCATECHOL IN PSEUDOMONAS. 4-AMINOSALICYLOYLGLUTAMINE & 4-AMINOSALICYLOYLGLYCINE IN MAN. /TABLE/|Blood from tuberculosis patients was cultured before, during, and after withdrawal of therapy involving five different drug combinations if isoniazid, thiacetazone, p-aminosalicyclic acid, and streptomycin. The approaches used to detect DNA damage were chromosome aberrations and sister chromatid exchanges (SCEs). A total of 179 subjects were analyzed. In combo these drugs showed synergistic, additive, and antagonistic effects, though they were found to be nonclastogenic individually. Four of the drug combinations, isoniazid plus thiacetazone, isoniazid plus p-aminosalicyclic acid, isoniazid plus thiacetazone plus streptomycin, and isoniazid plus p-aminosalicyclic acid plus streptomycin, induced a significant incr in the frequency of aberrations, whereas isoniazid plus streptomycin did not induce aberrations. In fact, streptomycin appeared to reduce the frequency of aberrations. SCEs were incr in only two patients: one treated with isoniazid plus thiacetazone and the other with isoniazid plus p-aminosalicyclic acid. The frequency of aberrations after withdrawal of therapy was decr; it was slightly higher than the controls, though it was insignificant. The return to normalcy could be due to elimination of damaged cells or the repair of DNA in lymphocytes. Though the drug-induced aberrations do not persist after withdrawal of therapy, the chromosome damaging combo of drugs should be used with caution, because the possibility of meiotic chromosome damage in germ cells (during therapy), which might be passed on to the next generation, cannot be ruled out.|For more Metabolism/Metabolites (Complete) data for P-AMINOSALICYLIC ACID (9 total), please visit the HSDB record page.

The drug has a half life of about 1 hour, and concentrations in plasma are negligible within 4 to 5 hours after a single conventional dose.

There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.|The antimicrobial activity of aminosalicylic acid is highly specific, and microorganisms other than Mycobacterium tuberculosis are unaffected. Most nontuberculous mycobacteria are not inhibited by the drug.|Aminosalicyclic acid is a structural analog of paraaminobenzoic acid, and its mechanism of action appears to be very similar to that of the sulfonamides. Since the sulfonamides are ineffective against Mycobacterium tuberculosis, and aminosalicyclic is inactive against sulfonamide susceptible bacteria, it is probable that the enzymes responsible for folate biosynthesis in various microorganisms may be quite exacting in their capacity to distinguish various analogs from the true metabolite.

SEVERE THERAPEUTIC MISADVENTURES, ALTHOUGH RARE, HAVE INCL...HEPATITIS...METHEMOGLOBINEMIA...|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. However, other studies have not found aminosalicylates to be teratogenic. /Aminosalicylates/|The literature has been reviewed for contact dermatitis occurring to antituberculosis agents. Of the 12 known drugs, 6 (isoniazid, rifampicin, ethambutol, p-aminosalicylic acid, streptomycin and kanamycin) have been documented by patch test to cause this type of dermatitis in certain individuals.

4 Aminosalicylic Acid

USP|Available commercially as the free acid and as the sodium dihydrate salt.

Benzoic acid, 4-amino-2-hydroxy-: ACTIVE

SPECTROPHOTOMETRY|A simple and fast analytical method for simultaneous determination of p-aminosalicyclic acid ... and m-aminophenol (3-aminophenol) by UV spectrophotometry in water, ethyl alcohol, and tetramethylurea is described. The method yields highly accurate and precise results and can be applied to pharmaceutical formulations.

Many drugs have been reported to interfere with copper-reduction or glucose oxidase tests used to measure urine glucose. ... The interfering drugs include ascorbic acid, beta-lactam antibiotics ... levodopa, and salicylates. Several other drugs may also interfere with certain urine glucose tests, but the interactions are poorly documented. These drugs include chloral hydrate, hyaluronidase, nalidixic acid, nitrofurantoin, p-aminosalicylic acid, phenazopyridine, probenecid, and X-ray contrast media. Drugs or their metabolites that are strong reducing substances produce false-positive results by the copper-reduction method and false-negative results by the glucose oxidase method. The beta-lactam antibiotic interfere with copper-reduction tests by producing copper compounds of various colors that confuse interpretation of test results.|A specific and sensitive HPLC assay for the determination of aminosalicylic acid ... sulfapyridine and their corresponding metabolites, and the pharmacokinetics of sulfapyridine and sulfasalazine ... in 7 healthy volunteers and 4 patients with Crohn's disease or ulcerative colitis are described.

Human drugs -> Orphan -> Granupas (previously Para-aminosalicylic acid Lucane) -> EMA Drug Category|Antimycobacterials -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients