Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Extended-Release Granules, Oral:
Paser: 4 g (30 ea)
Pharmacology
Mechanism of Action
Aminosalicylic acid (PAS) is a highly-specific bacteriostatic agent active against M. tuberculosis. Structurally related to para-aminobenzoic acid (PABA) and its mechanism of action is thought to be similar to the sulfonamides, a competitive antagonism with PABA; disrupts plate biosynthesis in sensitive organisms.
Pharmacokinetics/Pharmacodynamics
Absorption
Readily, >90%
Metabolism
Hepatic (>50%) via acetylation
Excretion
Urine (>80% as unchanged drug and metabolites)
Time to Peak
Serum: 6 hours
Half-Life Elimination
Reduced with renal impairment
Protein Binding
50% to 60%
Use in Specific Populations
Special Populations: Renal Function Impairment
Drug and its acetyl metabolite may accumulate.
Use: Labeled Indications
Adjunctive treatment of tuberculosis used in combination with other antitubercular agents
Contraindications
Hypersensitivity to aminosalicylic acid or any component of the formulation; severe renal impairment
Dosage and Administration
Dosing: Adult
Tuberculosis (second-line agent): Oral: 8 to 12 g/day (usually 4 g 2 to 3 times daily). Note: Use in combination with other antituberculous agents (Nahid 2016).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Tuberculosis (second-line agent):
Children ≤40 kg and Adolescents <15 years: Oral: 200 to 300 mg/kg/day (usually 100 mg/kg/dose 2 to 3 times daily). Note: Use in combination with other antituberculous agents (Nahid 2016).
Children >40 kg and Adolescents ≥15 years: Refer to adult dosing.
Administration
May be administered with food. Do not use granules if packet is swollen or if granules are discolored (ie, brown or purple). Granules may be sprinkled on applesauce or yogurt (do not chew) or suspended in tomato or orange juice.
Storage
Prior to dispensing, store granules below 15°C (59°F). Once dispensed store in refrigerator or freezer; packets may be stored at room temperature for short periods of time. Do not use if packet is swollen or if granules are dark brown or purple.
Drug Interactions
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy
Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy
Ammonium Chloride: May increase the serum concentration of Salicylates. Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Salicylates may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy
Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Monitor therapy
Blood Glucose Lowering Agents: Salicylates may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Carbonic Anhydrase Inhibitors: Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Exceptions: Brinzolamide; Dorzolamide. Consider therapy modification
Corticosteroids (Systemic): Salicylates may enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Monitor therapy
Dexketoprofen: Salicylates may enhance the adverse/toxic effect of Dexketoprofen. Dexketoprofen may diminish the therapeutic effect of Salicylates. Salicylates may decrease the serum concentration of Dexketoprofen. Management: The use of high-dose salicylates (3 g/day or more in adults) together with dexketoprofen is inadvisable. Consider administering dexketoprofen 30-120 min after or at least 8 hrs before cardioprotective doses of aspirin to minimize any possible interaction. Avoid combination
Ginkgo Biloba: May enhance the anticoagulant effect of Salicylates. Management: Consider alternatives to this combination of agents. Monitor for signs and symptoms of bleeding (especially intracranial bleeding) if salicylates are used in combination with ginkgo biloba. Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Consider therapy modification
Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving salicylates (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification
Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Avoid combination
Loop Diuretics: Salicylates may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Monitor therapy
Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Consider therapy modification
Potassium Phosphate: May increase the serum concentration of Salicylates. Monitor therapy
PRALAtrexate: Salicylates may increase the serum concentration of PRALAtrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern. Consider therapy modification
Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Monitor therapy
Salicylates: May enhance the anticoagulant effect of other Salicylates. Monitor therapy
Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. Avoid combination
Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Monitor therapy
Valproate Products: Salicylates may increase the serum concentration of Valproate Products. Monitor therapy
Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Specifically, the risk for Reye's syndrome may increase. Avoid combination
Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification
Adverse Reactions
Frequency not defined.
Cardiovascular: Pericarditis, vasculitis
Central nervous system: Brain disease
Dermatologic: Skin rash (including exfoliative dermatitis)
Endocrine & metabolic: Goiter (with or without myxedema), hypoglycemia, hypothyroidism
Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting
Hematologic & oncologic: Agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia
Hepatic: Hepatitis, jaundice
Miscellaneous: Fever
Ophthalmic: Optic neuritis
Respiratory: Eosinophilic pneumonitis
Warnings/Precautions
Concerns related to adverse effects:
- Salicylate sensitivity: Patients with sensitivity to tartrazine dyes, nasal polyps, and asthma may have an increased risk of salicylate sensitivity.
Disease-related concerns:
- Gastric ulcer: Use with caution in patients with gastric ulcer.
- Hepatic impairment: Use with caution in patients with hepatic impairment.
- Renal impairment: Use with caution in patients with renal impairment; contraindicated in patients with severe renal impairment.
Monitoring Parameters
Liver function; thyroid function
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects have been reported in animal reproduction studies. Salicylates have been noted to cross the placenta and enter fetal circulation. Aminosalicylic acid has been used safely during pregnancy; however, it should only be used if there are no alternatives for the treatment of multidrug-resistant tuberculosis (MMWR, 2003).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience abdominal pain or granule shell in stool. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), bruising, bleeding, confusion, chills, skin irritation, lack of appetite, severe nausea, vomiting, severe diarrhea, shortness of breath, excessive weight loss, night sweats, enlarged lymph nodes, sore throat, severe loss of strength and energy, or vision changes (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
