Introduction

Antituberculosis agent; structural analog of aminobenzoic acid.

Uses for Aminosalicylic Acid

Tuberculosis

Treatment of active (clinical) tuberculosis (TB) in conjunction with other antituberculosis agents. Designated an orphan drug by the US FDA for this use.

Second-line agent used in treatment of drug-resistant TB caused by Mycobacterium tuberculosis known or presumed to be susceptible to aminosalicylic acid.

For initial treatment of active TB caused by drug-susceptible M. tuberculosis, recommended multiple-drug regimens consist of an initial intensive phase (2 months) and a continuation phase (4 or 7 months). Although the usual duration of treatment for drug-susceptible pulmonary and extrapulmonary TB (except disseminated infections and TB meningitis) is 6–9 months, ATS, CDC, and IDSA state that completion of treatment is determined more accurately by the total number of doses and should not be based solely on the duration of therapy. A longer duration of treatment (e.g., 12–24 months) usually is necessary for infections caused by drug-resistant M. tuberculosis.

Patients with treatment failure or drug-resistant M. tuberculosis, including multidrug-resistant (MDR) TB (resistant to both isoniazid and rifampin) or extensively drug-resistant (XDR) TB (resistant to both isoniazid and rifampin and also resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial such as capreomycin, kanamycin, or amikacin), should be referred to or managed in consultation with experts in the treatment of TB as identified by local or state health departments or CDC.

Ulcerative Colitis and Crohn's Disease

Has been used in the treatment of mild to moderate ulcerative colitis^{† [off-label]} in patients intolerant of sulfasalazine. Also has been used in the treatment of Crohn's disease^{† [off-label]}. Designated an orphan drug by the US FDA for use in these conditions.

Usually, 5-aminosalicylic acid analogs (e.g., balsalazide, mesalamine, olsalazine) are used in the management of ulcerative colitis or Crohn's disease; aminosalicylic acid is a 4-aminosalicyclic acid analog.

Aminosalicylic Acid Dosage and Administration

Administration

Oral Administration

Administer orally. Has been administered IV, but a parenteral preparation is not commercially available in the US.

The delayed-release granules (Paser) have an acid-resistant coating designed to protect against degradation in the stomach so that the drug is released gradually and high peak concentrations are avoided.

To protect the acid-resistant coating, administer the granules in food or drink with a pH <5. The granules can be sprinkled on applesauce or yogurt. Alternatively, they can be suspended in a fruit drink (e.g., orange, apple, tomato, grapefruit, grape, or cranberry juices, “fruit punch”); the granules will sink in the juice and must be resuspended by swirling. The granules should be swallowed whole without chewing.

Patients receiving antacids do not need to take the delayed-release granules in an acidic food or drink.

Dosage

Should not be used alone for treatment of active (clinical) TB; must be given in conjunction with other antituberculosis agents.

Data not available to date to support use of aminosalicylic acid in intermittent (e.g., 1–3 times weekly) multiple-drug TB regimens.

Pediatric Patients

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

Children <15 years of age or weighing ≤40 kg: 200–300 mg/kg daily (up to 10 g daily) given in 2–4 divided doses recommended by ATS, CDC, IDSA, and AAP.

Adolescents ≥15 years of age: 8–12 g daily given in 2 or 3 divided doses recommended by ATS, CDC, and IDSA.

Adults

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

Manufacturer recommends 4 g 3 times daily.

8–12 g daily given in 2 or 3 doses recommended by ATS, CDC, and IDSA. There is some evidence that 4 g twice daily achieves target serum concentrations.

Prescribing Limits

Pediatric Patients

Treatment of Active (Clinical) Tuberculosis

Oral

Maximum 10 g daily recommended by ATS, CDC, IDSA, and AAP.

Special Populations

Hepatic Impairment

Dosage adjustment not necessary, but increased clinical and laboratory monitoring recommended. Clearance is not altered in patients with hepatic impairment, but these patients may not tolerate the drug as well as those with normal hepatic function.

Renal Impairment

Contraindicated in severe renal disease (end-stage renal disease).

Some experts recommend 4 g twice daily for treatment of active TB in patients with Cl_cr <30 mL/minute or undergoing hemodialysis. Doses should be given after hemodialysis since the drug is removed by this procedure; supplemental doses not necessary.

Contraindications

• Hypersensitivity to aminosalicylic acid or any ingredient in the formulation.

• Severe renal disease (end-stage renal disease).

Warnings/Precautions

Warnings

Hepatic Effects

Drug-induced hepatitis reported. Prompt recognition of symptoms and discontinuance of aminosalicylic acid usually results in recovery; failure to recognize the reaction has resulted in fatalities.

Initial symptoms usually appear within 3 months after the drug is initiated. Rash is the most common symptom; fever and GI disturbances (anorexia, nausea, diarrhea) may occur. Premonitory symptoms usually precede jaundice by several days or weeks (mean time to onset is 33 days; range 7–90 days). Hepatomegaly with lymphadenopathy, leukocytosis, and eosinophilia usually is present when hepatitis is diagnosed.

Monitor closely during the first 3 months of treatment. Immediately discontinue the drug at the first sign of a rash, fever, or other premonitory signs of intolerance.

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including fever, skin eruptions of various types, pruritus, vasculitis, exfoliative dermatitis, joint pain, eosinophilia, leukopenia, agranulocytosis, thrombocytopenia, hepatitis, and jaundice, reported.

If manifestations of hypersensitivity occur (e.g., rash, fever), immediately discontinue all drugs. After symptoms abate, cautiously reinitiate the drugs one at a time in small and gradually increasing doses to determine whether manifestations were drug-induced and, if so, which drug was responsible.

Desensitization

Desensitization has been used when reinitiation of the drug was considered necessary in a patient who had a hypersensitivity reaction.

One desensitization procedure used successfully in 15 of 17 patients involved an initial 10-mg dose of the drug, doubling dosage every 2 days until a total daily dosage of 1 g was reached, then continuing dosage escalation while giving the total daily dosage in divided doses according to the usual administration schedule (i.e., 3 times daily).

If mild temperature elevation or skin reaction develops during the desensitization procedure, manufacturer states desensitization may be continued by decreasing the dosage by one increment (i.e., to the previous level at which no reaction occurred) or maintaining current dosage for another 2-day cycle before continuing dosage progression. Such reactions are rare after a total daily aminosalicylic acid dosage of 1.5 g is reached.

General Precautions

Precautions Related to Treatment of Tuberculosis

Should not be used alone for treatment of active (clinical) TB; must be given in conjunction with other antituberculosis agents.

Clinical specimens for microscopic examination and mycobacterial cultures and in vitro susceptibility testing should be obtained prior to initiation of antituberculosis therapy and periodically during treatment to monitor therapeutic response. The antituberculosis regimen should be modified as needed. Patients with positive cultures after 4 months of treatment should be considered to have failed treatment (usually as the result of noncompliance or drug-resistant TB).

If added as a new drug to a regimen in patients experiencing treatment failure who have proven or suspected drug-resistant TB, at least 2 (preferably 3) new drugs known or expected to be active against the resistant strain should be added at the same time.

Compliance with the full course of antituberculosis therapy and all drugs included in the multiple-drug regimen is critical. Missed doses increase the risk of treatment failure and increase the risk that M. tuberculosis will develop resistance to the antituberculosis regimen.

To ensure compliance, ATS, CDC, IDSA, and AAP recommend that directly observed (supervised) therapy (DOT) be used for treatment of active TB whenever possible, especially when intermittent regimens are used, when the patient is immunocompromised or infected with HIV, or when drug-resistant M. tuberculosis is involved.

Malabsorption

Malabsorption of vitamin B₁₂, folic acid, iron, and lipids has occurred, possibly as the result of increased peristalsis. As a result of competition, a 5-g dose of aminosalicylic acid may reduce absorption of vitamin B₁₂ by about 55%; clinically important erythrocyte abnormalities may develop.

Consider using vitamin B₁₂ maintenance therapy in patients receiving aminosalicylic acid for >1 month.

Laboratory Monitoring

Assess hepatic enzyme concentrations and thyroid function prior to initiation of therapy. Assess thyroid function every 3 months.

Specific Populations

Pregnancy

Category C.

ATS, CDC, and IDSA state that, although aminosalicylic acid has been used safely during pregnancy, the drug should be used in pregnant women only when there are no alternatives for treatment of MDR TB.

Lactation

Distributed into milk.

Hepatic Impairment

Use with caution. Metabolism of aminosalicylic acid in patients with hepatic disease is comparable to that in healthy individuals, but such patients may tolerate aminosalicylic acid less well. (See Hepatic Effects under Cautions.)

Renal Impairment

Use with caution. Contraindicated in patients with severe renal disease (end-stage renal disease).

Patients with severe renal disease accumulate aminosalicylic acid and its acetyl metabolite but continue to acetylate the drug, resulting exclusively in the inactive acetylated form.

Common Adverse Effects

GI effects (nausea, vomiting, abdominal pain, diarrhea).

Administration

Oral Administration

Administer orally. Has been administered IV, but a parenteral preparation is not commercially available in the US.

The delayed-release granules (Paser) have an acid-resistant coating designed to protect against degradation in the stomach so that the drug is released gradually and high peak concentrations are avoided.

To protect the acid-resistant coating, administer the granules in food or drink with a pH <5. The granules can be sprinkled on applesauce or yogurt. Alternatively, they can be suspended in a fruit drink (e.g., orange, apple, tomato, grapefruit, grape, or cranberry juices, “fruit punch”); the granules will sink in the juice and must be resuspended by swirling. The granules should be swallowed whole without chewing.

Patients receiving antacids do not need to take the delayed-release granules in an acidic food or drink.

Dosage

Should not be used alone for treatment of active (clinical) TB; must be given in conjunction with other antituberculosis agents.

Data not available to date to support use of aminosalicylic acid in intermittent (e.g., 1–3 times weekly) multiple-drug TB regimens.

Pediatric Patients

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

Children <15 years of age or weighing ≤40 kg: 200–300 mg/kg daily (up to 10 g daily) given in 2–4 divided doses recommended by ATS, CDC, IDSA, and AAP.

Adolescents ≥15 years of age: 8–12 g daily given in 2 or 3 divided doses recommended by ATS, CDC, and IDSA.

Adults

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

Manufacturer recommends 4 g 3 times daily.

8–12 g daily given in 2 or 3 doses recommended by ATS, CDC, and IDSA. There is some evidence that 4 g twice daily achieves target serum concentrations.

Prescribing Limits

Pediatric Patients

Treatment of Active (Clinical) Tuberculosis

Oral

Maximum 10 g daily recommended by ATS, CDC, IDSA, and AAP.

Special Populations

Hepatic Impairment

Dosage adjustment not necessary, but increased clinical and laboratory monitoring recommended. Clearance is not altered in patients with hepatic impairment, but these patients may not tolerate the drug as well as those with normal hepatic function.

Renal Impairment

Contraindicated in severe renal disease (end-stage renal disease).

Some experts recommend 4 g twice daily for treatment of active TB in patients with Cl_cr <30 mL/minute or undergoing hemodialysis. Doses should be given after hemodialysis since the drug is removed by this procedure; supplemental doses not necessary.

Specific Drugs