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Aminosalicylic acid is an anti tubercular that is FDA approved for the treatment of tuberculosis. Common adverse reactions include abdominal pain, diarrhea, nausea, vomiting, hypersensitivity reaction, rash with fever.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Aminosalicylic acid is indicated for the treatment of tuberculosis in combination with other active agents. It is most commonly used in patients with Multi-drug Resistant TB (MDR-TB) or in situations when therapy with isoniazid and rifampin is not possible due to a combination of resistance and/or intolerance. When aminosalicylic acid is added to the treatment regimen in patients proven or suspected drug resistance, it should be accompanied by at least one and preferably two other new agents to which the patient's organism is known or expected to be susceptible.
- Aminosalicylic acid granules should be administered with other drugs to which the organism is known or expected to be susceptible. It is most commonly administered to patients with Multi-drug Resistant TB (MDR-TB) or in other situations in which therapy with isoniazid or rifampin is not possible due to a combination of resistance and/or intolerance. The adult dosage of four grams (one packet) three times per day or correspondingly smaller doses in children should be given by sprinkling on apple sauce or yogurt or by swirling in the glass to suspend the granules in an acidic drink such as tomato or orange juice.
- DO NOT USE if packet is swollen or the granules have lost their tan color, turning dark brown or purple.
Off-Label Use and Dosage (Adult)
There is limited information regarding Off-Label Guideline-Supported Use of Aminosalicylic acid in adult patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Aminosalicylic acid in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-labeled indications and dosage of Aminosalicylic acid in pediatric patients.
Off-Label Use and Dosage (Pediatric)
There is limited information regarding Off-Label Guideline-Supported Use of Aminosalicylic acid in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Aminosalicylic acid in pediatric patients.
- Patients with severe renal disease will accumulate aminosalicylic acid and its acetyl metabolite but will continue to acetylate, thus leading exclusively to the inactive acetylated form; deacetylation, if any, is not significant.
- The half life of free aminosalicylic acid in renal disease is 30.8 minutes in comparison to 26.4 minutes in normal volunteers. but the half life of the inactive metabolite is 309 minutes in uremic patients in comparison to 51 minutes in normal volunteers. Although aminosalicylic acid passes dialysis membranes, the frequency of dialysis usually is not comparable to the half-life of 50 minutes for the free acid. * Patients with end stage renal disease should not receive aminosalicylic acid.
- In one retrospective study of 7492 patients on rapidly absorbed aminosalicylic acid preparations, drug-induced hepatitis occurred in 38 patients (0.5%); in these 38 the first symptom usually appeared within three months of the start of therapy with a rash as the most common event followed by fever and much less frequently by GI disturbances of anorexia, nausea or diarrhea. Only one patient was diagnosed on routine biochemistry.
- Premonitory symptoms in 90% of these 38 patients preceded jaundice by a few days to several weeks with the mean time of onset 33 days with a range of 7-90 days. Half of the adverse reactions occurred during the third, fourth or fifth weeks. When aminosalicylic acid-induced hepatitis was diagnosed, hepatomegaly was invariably present with lymphadenopathy in 46%, leucocytosis in 79%, and eosinophilia in 55%. Prompt recognition with discontinuation led to the recovery of all 38 patients. If recognized in the premonitory stage, the reaction is reported to “settle” in 24 hours and no jaundice ensues. From other reported studies failure to recognize the reaction can result in a mortality of up to 21%. The patient must be monitored carefully during the first three months of therapy and treatment must be discontinued immediately at the first sign of a rash, fever or other premonitory signs of intolerance.
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Aminosalicylic acid in the drug label.
- The most common side effect is gastrointestinal intolerance manifested by nausea, vomiting, diarrhea, and abdominal pain.
- Hypersensitivity reactions: Fever, skin eruptions of various types, including exfoliative dermatitis, infectious mononucleosis-like, or lymphoma-like syndrome, leucopenia, agranulocytosis, thrombocytopenia, Coombs' positive hemolytic anemia, jaundice, hepatitis, pericarditis, hypoglycemia, optic neuritis, encephalopathy, Leoffler's syndrome, vasculitis and a reduction in prothrombin.
- Crystalluria may be prevented by the maintenance of urine at a neutral or an alkaline pH.
There is limited information regarding Aminosalicylic acid Drug Interactions in the drug label.
Use in Specific Populations
- Aminosalicylic acid has been reported to produce occipital malformations in rats when given at doses within the human dose range. Although there probably is a dose response, the frequency of abnormalities was comparable to controls at the highest level tested (two times the human dosage). When administered to rabbits at 5 mg/kg, throughout all three trimesters, no teratologic or embryocidal effects were seen. Literature reports on aminosalicylic acid in pregnant women always report coadministration of other medications. Because there are no adequate and well controlled studies of aminosalicylic acid in humans, aminosalicylic acid granules should be given to a pregnant woman only if clearly needed.
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Aminosalicylic acid in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Aminosalicylic acid during labor and delivery.
- After administration of a different preparation of aminosalicylic acid to one patient, the maximum concentration in the milk was 1 μg/mL at 3 hours with a half-life of 2.5 hours; the maximum maternal plasma concentration was 70 μg/mL at two hours.
There is no FDA guidance on the use of Aminosalicylic acid with respect to pediatric patients.
There is no FDA guidance on the use of Aminosalicylic acid with respect to geriatric patients.
There is no FDA guidance on the use of Aminosalicylic acid with respect to specific gender populations.
There is no FDA guidance on the use of Aminosalicylic acid with respect to specific racial populations.
There is no FDA guidance on the use of Aminosalicylic acid in patients with renal impairment.
There is no FDA guidance on the use of Aminosalicylic acid in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Aminosalicylic acid in women of reproductive potentials and males.
There is no FDA guidance one the use of Aminosalicylic acid in patients who are immunocompromised.
Administration and Monitoring
- The patient must be monitored carefully during the first three months of therapy and treatment must be discontinued immediately at the first sign of a rash, fever or other premonitory signs of intolerance.
There is limited information regarding IV Compatibility of Aminosalicylic acid in the drug label.
- Overdosage has not been reported.
There is limited information regarding Aminosalicylic acid Pharmacology in the drug label.
Mechanism of Action
- Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. The mechanism of action has been postulated to be inhibition of folic acid synthesis (but without potentiation with antifolic compounds) and/or inhibition of synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.
- Aminosalicylic acid granules are a delayed release granule preparation of aminosalicylic acid (p-aminosalicylic acid; 4-aminosalicylic acid) for use with other anti-tuberculosis drugs for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The granules are designed for gradual release to avoid high peak levels not useful (and perhaps toxic) with bacteriostatic drugs. Aminosalicylic acid is rapidly degraded in acid media; the protective acid-resistant outer coating is rapidly dissolved in neutral media so a mildly acidic food such as orange, apple or tomato juice, yogurt or apple sauce should be used.
- Aminosalicylic acid (p-aminosalicylic acid) is 4-Amino-2-hydroxybenzoic acid. aminosalicylic acid granules are the free base of aminosalicylic acid and do NOT contain sodium or a sugar. The molecular formula is C7H7NO3 with a molecular weight of 153.14. With heat p-aminosalicylic acid is decarboxylated to produce CO2 and m-aminophenol. If the airtight packets are swollen, storage has been improper. DO NOT USE if packets are swollen or the granules have lost their tan color and are dark brown or purple.
They are supplied as off-white tan colored granules with an average diameter of 1.5 mm and an average content of 60% aminosalicylic acid by weight. The acid resistant outer coating will be completely removed by a few minutes at a neutral pH. The inert ingredients are:
- Colloidal silicon dioxide
- Dibutyl sebacate
- Hydroxypropyl methyl cellulose
- Methacrylic acid copolymer
- Microcrystalline cellulose
- The packets contain 4 grams of aminosalicylic acid for oral administration three times a day by sprinkling on apple sauce or yogurt to be eaten without chewing.
- Suspension in an acidic fruit drink such as orange juice or tomato juice will protect the coating for at least 2 hours. Swirling the juice in the glass will help resuspend the granules if they sink.
There is limited information regarding Pharmacodynamics of Aminosalicylic acid in the drug label.
- Characteristics: 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. Both are discussed below.
- After two hours in simulated gastric fluid, 10% of unprotected aminosalicylic acid is decarboxylated to form meta-aminophenol, a known hepatotoxin. The acid-resistant coating of the Aminosalicylic acid granules protects against degradation in the stomach. The small granules are designed to escape the usual restriction on gastric emptying of large particles. Under neutral conditions such as are found in the small intestine or in neutral foods, the acid-resistant coating is dissolved within one minute. Care must be taken in the administration of these granules to protect the acid-resistant coating by maintaining the granules in an acidic food during dosage administration. Patients who have neutralized gastric acid with antacids will not need to protect the acid resistant coating with an acidic food since no acid is present to spoil the drug. Antacids may influence the absorption of other medications and are not necessary for aminosalicylic acid consumed with an acidic food.
- Because aminosalicylic acid granules are protected by an enteric coating absorption does not commence until they leave the stomach; the soft skeletons of the granules remain and may be seen in the stool.
- Absorption and excretion: In a single 4 gram pharmacokinetic study with food in normal volunteers the initial time to a 2μg/mL serum level of aminosalicylic acid was 2 hours with a range of 45 minutes to 24 hours; the median time to peak was 6 hours with a range of 1.5 to 24 hours; the mean peak level was 20 μg/mL with a range of 9 to 35 μg/mL; a level of 2 μg/mL was maintained for an average of 7.9 hours with a range of 5 to 9; a level of 1 μg/mL was maintained for an average of 8.8 hours with a range of 6 to 11.5 hours. The recommended schedule is 4 grams every 8 hours.
- 80% of aminosalicylic acid is excreted in the urine, with 50% or more of the dosage excreted in acetylated form. The acetylation process is not genetically determined as is the case for isoniazid. Aminosalicylic acid is excreted by glomerular filtration; although previously reported otherwise, probenecid, a tubular blocking agent, does not enhance plasma concentration. In a 1954 study thyroxine synthesis but not iodide uptake was reported reduced about 40% when the sodium salt (not aminosalicylic acid granules) of aminosalicylic acid was administered one hour before radio-iodine; the sodium salt typically produces a serum level over 120 μg/mL at one hour lasting one hour. Occasional goiter development can be prevented by the administration of thyroxine but not iodide.
- Penetration into the cerebrospinal fluid occurs only if the meminges are inflamed.
- Approximately 50-60% of aminosalicylic acid is protein bound; binding is reported to be reduced 50% in kwashiorkor.
- Microbiology: The aminosalicylic acid MIC for M. tuberculosis in 7H11 agar was less than 1.0 μg/mL for nine strains including three multidrug resistant strains, but 4 and 8 μg/mL for two other multidrug resistant strains. The 90% inhibition in 7H12 broth (Bactec) showed little dose response but was interpreted as being less than or equal to 0.12-0.25 μg/mL for eight strains of which three were multi-resistant, 0.50 μg/mL for one resistant strain, questionable for four non-resistant strains and greater than 1μg/mL for one non-resistant and three resistant strains. Aminosalicylic acid is not active in vitro against M. avium.
There is limited information regarding Nonclinical Toxicology of Aminosalicylic acid in the drug label.
There is limited information regarding Clinical Studies of Aminosalicylic acid in the drug label.
- Carton of 30 aminosalicylic acid packets (NDC 49938-107-04).
- Each packet contains four grams aminosalicylic acid.
- Aminosalicylic acid granules are supplied in packets containing 4 grams of aminosalicylic acid for administration three times a day by suspension in an acidic drink or food with a pH less than 5. Examples include apple sauce, yogurt, tomato or orange juice.
- Distributors and Pharmacists: Store below 59°F (15°C) (in a refrigerator or freezer).
- Patients are urged to store aminosalicylic acid in a refrigerator or freezer. Aminosalicylic acid packets may be stored at room temperature for short periods of time.
- AVOID EXCESSIVE HEAT. DO NOT USE if packet is swollen or the granules have lost their tan color, turning dark brown or purple.
Package and Label Display Panel
|This image of the FDA label is provided by the National Library of Medicine.|
|This image of the FDA label is provided by the National Library of Medicine.|
Patient Counseling Information
There is limited information regarding Patient Counseling Information of Aminosalicylic acid in the drug label.
Precautions with Alcohol
- Alcohol-Aminosalicylic acid interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Look-Alike Drug Names
There is limited information regarding Aminosalicylic acid Look-Alike Drug Names in the drug label.
The contents of this FDA label are provided by the National Library of Medicine.