Usage
Sodium aminosalicylate, also known as para-aminosalicylic acid (PAS), is an antibiotic primarily used in combination with other antituberculosis medications for the treatment of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). It is also used in cases where first-line drugs like isoniazid and rifampicin cannot be used due to resistance or intolerance. It is classified as an aminosalicylate, a subclass of antimycobacterials. The mechanism of action involves inhibition of folic acid synthesis within the Mycobacterium tuberculosis bacteria. It may also disrupt cell wall component synthesis, further hindering bacterial growth. Primarily, it exhibits bacteriostatic activity but can become bactericidal at higher concentrations. By including PAS in a combination regimen, the emergence of bacterial resistance to other antituberculosis medications can be slowed.
Alternate Names
- Para-aminosalicylic acid (PAS)
- 4-Aminosalicylic acid
- P-Aminosalicylic acid sodium salt
- Brand names: Paser®, Nemasol Sodium®, Granupas® (Note: Brand availability may vary by region).
How It Works
Pharmacodynamics: Sodium aminosalicylate is a bacteriostatic agent, primarily targeting Mycobacterium tuberculosis. It interferes with folic acid synthesis, essential for bacterial growth and replication. This action occurs through competitive inhibition of dihydropteroate synthase, an enzyme necessary for folate production. Additionally, PAS may inhibit mycobactin synthesis, a component crucial for iron uptake by the bacteria.
Pharmacokinetics:
- Absorption: Administered orally as delayed-release granules to minimize gastrointestinal side effects. Absorption occurs mainly in the small intestine. Food may slow absorption but does not significantly affect overall bioavailability.
- Distribution: Distributed widely throughout the body, including into breast milk.
- Metabolism: Undergoes acetylation in the liver to form N-acetyl-PAS, the major metabolite. This process can be influenced by individual genetic variations, affecting drug efficacy and toxicity.
- Elimination: Primarily excreted through the kidneys, with a small amount in feces. Dose adjustment is crucial in patients with renal impairment to prevent drug accumulation and toxicity.
Dosage
Standard Dosage
Adults:
- The standard adult dose is 4 grams of para-aminosalicylic acid (equivalent to approximately 9.2 grams of sodium aminosalicylate delayed-release granules or two 5.52g sachets of PAS sodium) twice daily. The maximum daily dose is 12 grams of PAS acid.
- Administer the granules dissolved in water or acidic fruit juice (e.g., orange juice) after meals to reduce gastric irritation.
Children:
- The pediatric dose is 150 mg/kg/day of PAS acid (equivalent to 345mg/kg/day of sodium aminosalicylate) divided into two equal doses. It is crucial to accurately measure doses for children, using the provided measuring spoon for granules.
- Do not exceed the maximum adult dose in children.
- In children under one year old, particularly those under six months old, the sodium content of sodium aminosalicylate should be considered and minimized from other dietary sources.
Special Cases:
- Elderly Patients: Limited data available; caution is recommended, and dosage should be individualized based on renal function.
- Patients with Renal Impairment: Contraindicated in severe renal impairment. Dose adjustment is necessary in patients with moderate to mild renal impairment. Reduce the dose and monitor closely.
- Patients with Hepatic Dysfunction: No dose adjustment is typically required, but close monitoring of liver function is recommended.
- Patients with Comorbid Conditions: Use with caution in patients with a history of gastric or duodenal ulcers, heart failure, or thyroid disorders. Sodium content needs consideration in those on sodium-restricted diets.
Clinical Use Cases
Sodium aminosalicylate is not typically used in these clinical settings (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations). Its primary role is in the long-term treatment of drug-resistant tuberculosis.
Dosage Adjustments
Dose adjustments are necessary in renal impairment and potentially in elderly patients. Genetic polymorphisms affecting acetylation might require personalized dosing strategies.
Side Effects
Common Side Effects
- Nausea, vomiting, diarrhea, abdominal pain (gastrointestinal disturbances)
- Loss of appetite
- Headache
Rare but Serious Side Effects
- Hepatotoxicity (liver damage)
- Hypersensitivity reactions (fever, rash, eosinophilia)
- Hypothyroidism
- Methemoglobinemia
- Acute intolerance syndrome (fever, abdominal pain, rash, malaise)
- Myocarditis
- Pericarditis
- Drug-induced lupus
Long-Term Effects
- Chronic liver damage (with prolonged use)
- Malabsorption syndrome
- Vitamin B12 deficiency
Adverse Drug Reactions (ADR)
Severe hypersensitivity reactions, hepatotoxicity, and acute intolerance syndrome require immediate discontinuation of the drug and supportive care.
Contraindications
- Hypersensitivity to aminosalicylic acid or any of its components
- Severe renal impairment
- Severe liver failure
- Severe heart failure
- Gastric or duodenal ulcers
- Myxedema
Drug Interactions
- Probenecid (increases PAS levels)
- Anticoagulants (increased bleeding risk)
- Rifampicin, isoniazid, ethionamide (potential interactions; monitor closely)
- Digoxin (decreased digoxin absorption)
Pregnancy and Breastfeeding
- Pregnancy Category C: Use with caution if benefits outweigh risks. PAS can cross the placenta and potentially cause fetal harm, including thyroid dysfunction.
- Breastfeeding: PAS is excreted in breast milk. Breastfeeding should be avoided while taking PAS.
Drug Profile Summary
- Mechanism of Action: Inhibits folic acid synthesis and possibly mycobactin synthesis in M. tuberculosis.
- Side Effects: Nausea, vomiting, diarrhea, abdominal pain, hepatotoxicity, hypersensitivity.
- Contraindications: Severe renal/hepatic impairment, heart failure, hypersensitivity.
- Drug Interactions: Probenecid, anticoagulants, rifampicin, isoniazid, digoxin.
- Pregnancy & Breastfeeding: Use with caution in pregnancy; avoid breastfeeding.
- Dosage: Adults: 4g PAS acid BID. Children: 150mg/kg/day PAS acid divided BID.
- Monitoring Parameters: Liver function tests, renal function tests, thyroid function tests, complete blood count.
Popular Combinations
Sodium aminosalicylate is often used in combination with other antituberculosis drugs, specifically in MDR-TB and XDR-TB treatment regimens. Combinations are determined on a case-by-case basis according to susceptibility testing and clinical guidelines.
Precautions
- Monitor liver and renal function.
- Assess for hypersensitivity reactions.
- Administer after meals.
- Monitor thyroid function.
- Minimize sodium intake from other sources in infants, particularly under six months old.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sodium aminosalicylate?
A: Adults: 4 grams of para-aminosalicylic acid (equivalent to about 9.2 grams of sodium aminosalicylate) twice daily. Children: 150 mg/kg/day of PAS acid (equivalent to 345 mg/kg/day of sodium aminosalicylate) divided twice daily.
Q2: What are the most common side effects?
A: Gastrointestinal side effects like nausea, vomiting, diarrhea, and abdominal pain are common.
Q3: What are the serious side effects to watch for?
A: Hepatotoxicity, hypersensitivity reactions, and acute intolerance syndrome are potentially serious and require immediate attention.
Q4: Is sodium aminosalicylate safe in pregnancy?
A: Pregnancy Category C: Use with caution if benefits outweigh risks. Fetal risks exist, particularly regarding thyroid function.
Q5: Can I breastfeed while taking sodium aminosalicylate?
A: It is recommended to avoid breastfeeding due to drug excretion in breast milk.
Q6: What should I do if a dose is missed?
A: Take the missed dose as soon as remembered. Do not double the dose.
Q7: How is sodium aminosalicylate administered?
A: Orally, as delayed-release granules dissolved in water or acidic fruit juice after meals.
Q8: Why is sodium aminosalicylate used in combination with other drugs?
A: Combination therapy helps prevent the development of drug resistance in M. tuberculosis.
Q9: Does sodium aminosalicylate interact with any other medications?
A: Yes, it can interact with probenecid, anticoagulants, rifampicin, isoniazid, and digoxin.
Q10: What monitoring parameters are important during therapy?
A: Liver function tests, renal function tests, thyroid function tests, and complete blood counts are essential monitoring parameters.
Please note that this information is current as of February 17, 2025, and is subject to change as new research emerges. Always consult with updated medical resources and individual patient considerations when making clinical decisions.
