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Aminosalicylic Acid


General


Pronunciation

(a mee noe sal i SIL ik AS id)


Brand Names: U.S.

  • Paser

Indications


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


Dosing and Administration


Dosing: Adult

Tuberculosis: Oral: 8-12 g/day in 2-3 divided doses (Note: Studies have shown administration of 4 g twice daily is adequate to achieve the target serum concentration) (MMWR, 2003)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Tuberculosis: Oral: 200-300 mg/kg/day in 2-4 divided doses


Dosing: Renal Impairment

No dosage adjustment provided in manufacturer 's labeling; however, the following adjustments have been used by some clinicians:

Aronoff, 2007:

CrCl >50 mL/minute: No dosage adjustment necessary

CrCl 10-50 mL/minute: Administer 50% to 75% of dose

CrCl <10 mL/minute: Administer 50% of dose

Administer after hemodialysis: Administer 50% of dose

Continuous arteriovenous hemofiltration: Dose for CrCl <10 mL/minute

MMWR, 2003:

CrCl ≥30 mL/minute: No dosage adjustment necessary

CrCl <30 mL/minute: 4 g twice daily


Dosing: Hepatic Impairment

Use with caution


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.


Dietary Considerations

May be taken with food.


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.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Packet, Oral:

Paser: 4 g (30 ea)


Drug Interactions

ACE Inhibitors: Salicylates may enhance the nephrotoxic effect of ACE Inhibitors. Salicylates may diminish the therapeutic effect of ACE Inhibitors. Monitor therapy

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

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, Reyes 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

NSAID (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Consider therapy modification

Potassium Acid 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

Treprostinil: May enhance the adverse/toxic effect of Salicylates. 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. Reye's Syndrome may develop. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification


Monitoring Parameters

Liver function at baseline; thyroid function (at baseline and every 3 months with prolonged therapy [>3 months]) (MMWR, 2003)


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


Special Populations: Renal Function Impairment

Drug and its acetyl metabolite may accumulate.


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.


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).


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Pharmacology

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.


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%


Patient and Family Education


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 liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), bruising, bleeding, confusion, chills, severe skin irritation, lack of appetite, severe nausea, severe vomiting, severe diarrhea, shortness of breath, excessive weight loss, night sweats, enlarged lymph nodes, pharyngitis, 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 healthcare 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.

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