Tuberculosis, drug resistant (alternative agent): Note: Expert consultation for optimal regimen and duration of treatment is advised.
Oral: 4 g two to three times daily as part of an appropriate combination regimen (ATS/CDC/ERS/IDSA [Nahid 2019]).
CrCl ≥30 mL/minute: No dosage adjustment necessary (ATS/CDC/IDSA [Nahid 2016]).
CrCl <30 mL/minute: Contraindicated in patients with severe impairment in the manufacturer’s labeling; however, some experts suggest a dose of 4 g twice daily (Alsultan 2014; ATS/CDC/IDSA [Nahid 2016]).
Patients on hemodialysis: Contraindicated in patients with end-stage renal disease in the manufacturer’s labeling; however, some experts suggest a dose of 4 g twice daily, administered after hemodialysis on dialysis days (ATS/CDC/IDSA [Nahid 2016]).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution
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.
There are no dosage adjustments provided in the manufacturer's labeling; contraindicated in severe impairment.
There are no dosage adjustments provided in the manufacturer's labeling; contraindicated in severe impairment.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Packet, Oral:
Paser: 4 g (30 ea [DSC])
No
Oral: 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 an acidic beverage (eg, tomato or orange juice).
Oral: 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.
Tuberculosis: Treatment of tuberculosis, as part of an appropriate combination regimen, in the setting of multidrug resistance or intolerance to other agents.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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
Hypersensitivity to aminosalicylic acid or any component of the formulation; severe or end-stage renal disease
Concerns related to adverse effects:
• Salicylate sensitivity: Patients with nasal polyps and asthma may have an increased risk of salicylate sensitivity.
Disease-related concerns:
• 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 or end-stage renal disease.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Risk C: Monitor therapy
Agents with Blood Glucose Lowering Effects: Salicylates may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy
Ammonium Chloride: May increase the serum concentration of Salicylates. Risk C: 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. Risk C: Monitor therapy
Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Risk C: 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. Risk D: 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. Risk C: Monitor therapy
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: 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. Risk X: 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. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk C: Monitor therapy
Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Risk X: Avoid combination
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Loop Diuretics: Salicylates may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: 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. Management: Consider avoiding coadministration of methotrexate and salicylates. If coadministration cannot be avoided, monitor for increased toxic effects of methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
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). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Salicylates. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of salicylates and topical NSAIDs is not recommended. If salicylates and topical NSAIDs are coadministered, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification
Potassium Phosphate: May increase the serum concentration of Salicylates. Risk C: 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. Management: Consider avoiding concomitant use of salicylates and pralatrexate. If coadministered, monitor for increased pralatrexate adverse effects. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk X: Avoid combination
Salicylates: May enhance the anticoagulant effect of other Salicylates. Risk C: Monitor therapy
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. Risk X: Avoid combination
Tenofovir Disoproxil Fumarate: Aminosalicylic Acid may decrease the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Valproate Products: Salicylates may increase the serum concentration of Valproate Products. Risk C: 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. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Avoid as needed use of salicylates in patients taking vitamin K antagonists. Aspirin (80 to 325 mg/day) may be used with warfarin for prevention of cardiovascular events. If coadministering salicylates and vitamin K antagonists, monitor for bledding. Risk D: Consider therapy modification
Evaluate pregnancy status prior to treatment of multidrug-resistant tuberculosis in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment for multidrug-resistant tuberculosis (Esmail 2018).
Active tuberculosis infection is associated with adverse fetal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020), as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020).
Data are limited for use of second-line drugs in pregnancy (ie, aminosalicylic acid). Individualized regimens should be utilized to treat multidrug-resistant tuberculosis in pregnant patients; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020).
Aminosalicylic acid is present in breast milk.
Following the administration of oral aminosalicylic acid 4 g to a lactating woman (postpartum age not presented), peak maternal serum concentrations were 70.1 mcg/mL at 1 hour, peak breast milk concentrations were 1.1 mcg/mL at 3 hours, and the half-life of aminosalicylic acid in the breast milk was calculated to be 2.5 hours (Holdiness 1984). Using the peak breast milk concentration from this single case report, the relative infant dose (RID) of aminosalicylic acid was calculated to be <1% compared to an infant therapeutic dose of 200 to 300 mg/day (Tran 1998). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). Because information is limited, infants exposed to aminosalicylic acid via breast milk should be monitored for adverse events such as anorexia, diarrhea, nausea, vomiting, or hypersensitivity reactions (Tran 1998).
Patients with multidrug-resistant tuberculosis and a sputum smear-positive test should avoid breastfeeding when possible (Esmail 2018).
Liver function; thyroid function; CBC; serum electrolytes (AST/CDC/ERS/IDSA [Nahid 2019]); serum concentrations (peak) as clinically indicated (Asultan 2014).
Timing of serum samples: Draw peak approximately 6 hours postdose (Alsultan 2014).
Therapeutic level: Peak: 20 to 60 mcg/mL; consider dose increase if <10 mcg/mL (Alsultan 2014).
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%
Protein binding: 50% to 60%
Metabolism: Hepatic (>50%) via acetylation
Half-life elimination: Reduced with renal impairment
Time to peak, serum: 6 hours
Excretion: Urine (>80% as unchanged drug and metabolites)
Altered kidney function: Drug and its acetyl metabolite may accumulate.
Pack (Paser Oral)
4 g (per each): $8.00
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