Balsalazide Disodium (balsalazide disodium)

No dosing information is available for this tab.

No dosing information is available for this tab.

No formal drug interaction studies have been performed.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Aspirin (> 325 Mg); Salicylates/Dichlorphenamide

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Dichlorphenamide may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system).(1) Alternatively, toxicity may be due to salicylate-induced displacement of dichlorphenamide from its protein binding sites and inhibition of renal tubular secretion.

CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. Anorexia, tachypnea, lethargy, and coma have been reported.(1)

PREDISPOSING FACTORS: High doses of salicylates, low body weight.

PATIENT MANAGEMENT: The concurrent use of high-dose aspirin or other salicylates with dichlorphenamide is contraindicated. If it is necessary to administer a low-dose salicylate concurrently, use the lowest dose possible or replace it with a non-salicylate anti-inflammatory agent. Monitor salicylate levels and serum bicarbonate concentrations, and monitor the patient for symptoms of toxicity. Adjust the dose as needed.(1)

DISCUSSION: An 8-year-old boy with unimpaired renal and hepatic function was found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of aloxiprin 3.6 gram daily and dichlorphenamide 25 mg three times daily. His symptoms resolved after discontinuation of both aloxiprin and dichlorphenamide and did not recur on subsequent therapy with naproxen and dichlorphenamide.(2) A 75-year old woman taking dichlorphenamide 100 mg to 150 mg daily for therapy of glaucoma and high doses of aspirin (975 mg 4 to 5 times daily) for arthritis developed severe acid-base imbalance and salicylate intoxication. The patient did not exhibit ill effects when taking high aspirin doses without dichlorphenamide.(3)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Select Salicylates/Methotrexate (Low Strength Inj, Oral)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Salicylates may inhibit the renal tubular excretion of methotrexate.

CLINICAL EFFECTS: The concurrent use of methotrexate and salicylates may result in an increase in the therapeutic and toxic effects of methotrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia.

PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Anti-inflammatory doses of aspirin/salicylates - impaired renal function, ascites, or pleural effusions

PATIENT MANAGEMENT: US manufacturer prescribing information for methotrexate states nonsteroidal anti-inflammatory drugs, including salicylates should not be administered prior to or concomitantly with high doses of methotrexate. If concurrent therapy is warranted, methotrexate plasma levels should be monitored and patients should be observed for methotrexate toxicity. The dosage of methotrexate may need to be adjusted. Use caution when administering salicylates and low dose methotrexate. Salicylate doses > or = 2 grams per day have been associated with hepatic impairment or impaired renal elimination of methotrexate. It would be prudent to avoid high-dose aspirin, especially in patients with renal impairment or near the time of methotrexate dosage (in patients receiving weekly therapy). The Australian prescribing information for aspirin DL-lysine states coadministration with methotrexate at doses of 15 mg/week or greater is contraindicated.

DISCUSSION: Several studies and case reports have reported increased and prolonged methotrexate levels in patients receiving concurrent aspirin. One study noted an effect with average weekly doses of methotrexate of 16.6 mg, but not weekly doses of 7.5 mg. Decreased renal function has also been reported with the combination. Single ingredient aspirin or buffered aspirin products with strengths < or = to 325 mg or formulations which are associated with once daily use for cardiovascular protection are not linked to this interaction. Other lower-strength aspirin formulations (e.g. headache, cough & cold, opioid combinations) which could be consumed multiple times a day remain linked to this interaction.

Selected Salicylates/Methotrexate (Oncology-Injection)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Salicylates may inhibit the renal tubular excretion of methotrexate.

CLINICAL EFFECTS: The concurrent use of methotrexate and salicylates may result in an increase in the therapeutic and toxic effects of methotrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia.

PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Anti-inflammatory doses of aspirin/salicylates - Impaired renal function, ascites, or pleural effusions

PATIENT MANAGEMENT: US manufacturer prescribing information for methotrexate states nonsteroidal anti-inflammatory drugs should not be administered prior to or concomitantly with high doses of methotrexate. If concurrent therapy is warranted, methotrexate plasma levels should be monitored and patients should be observed for methotrexate toxicity. The dosage of methotrexate may need to be adjusted. Use caution when administering higher doses of salicylates with lower doses of methotrexate. Salicylate doses > or = 2 grams per day have been associated with hepatic impairment or impaired renal elimination of methotrexate. It would be prudent to avoid high-dose aspirin, especially in patients with renal impairment or near the time of methotrexate dosage (in patients receiving weekly therapy). The Australian prescribing information for aspirin DL-lysine states coadministration with methotrexate at doses of 15 mg/week or greater is contraindicated.

DISCUSSION: Several studies and case reports have reported increased and prolonged methotrexate levels in patients receiving concurrent aspirin. One study noted an effect with average weekly doses of methotrexate of 16.6 mg, but not weekly doses of 7.5 mg. Decreased renal function has also been reported with the combination. Single ingredient aspirin or buffered aspirin products with strengths < or = to 325 mg or formulations which are associated with once daily use for cardiovascular protection are not linked to this interaction. Other lower-strength aspirin formulations (e.g. headache, cough & cold, opioid combinations) which could be consumed multiple times a day remain linked to this interaction.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Aminosalicylate Derivatives/Azathioprine; Mercaptopurine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is not known. Aminosalicylic acid and its derivatives (balsalazide, mesalamine, olsalazine, sulfasalazine) may inhibit azathioprine or mercaptopurine inactivation via the thiopurine methyltransferase (TPMT) pathway. Aminosalicylates, azathioprine and mercaptopurine are all associated risk for neutropenia, thrombocytopenia, and anemia and so these risks could be additive.

CLINICAL EFFECTS: Concurrent use of azathioprine or mercaptopurine with aminosalicylates may increase the risk for anemia, neutropenia, or thrombocytopenia.

PREDISPOSING FACTORS: Patients with reduced or absent thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) activity are at higher risk of accumulating thiopurine metabolites and severe myelosuppression. Approximately 0.3 % of patients of European, Latino, or African descent have mutations of the TPMT gene resulting in little to no TPMT activity (homozygous deficiency), and approximately 10 % have intermediate TPMT activity (heterozygous deficiency). NUDT15 deficiency is not seen in patients of African descent and is seen in less than 1 % of patients of European descent. Approximately 1 % of patients of East Asian descent, 0.5 % of patients of central/south Asian descent, and 2 % of patients of Latino descent have homozygous NUDT15 deficiency. About 17 % of patients of East Asian descent, 13 % of patients of central/south Asian descent, and 8 % of patients of Latino descent have heterozygous NUDT15 deficiency. Added risk for myelosuppression would be expected in patients who also receive allopurinol or other agents which block xanthine oxidase (XO), the other major inactivation pathway for azathioprine and mercaptopurine.

PATIENT MANAGEMENT: Use the lowest possible dose of each drug and monitor closely for myelosuppression.

DISCUSSION: Manufacturer prescribing information states that concurrent use of aminosalicylates with azathioprine or mercaptopurine has been reported to cause bone marrow suppression. In a prospective study, 22 inflammatory bowel disease (IBD) patients on concurrent 5-aminosalicylate with (2 g daily and later increased to 4 g daily) with azathioprine had increased levels of 6-thioguanine (6-TGN) metabolites. One patient had signs of myelosuppression.(3) A prospective study in 183 IBD patients on concurrent 5-aminosalicylic acid and thiopurines found no significant interaction between thiopurines and 5-aminosalicylic acid.(4) A retrospective study in 199 IBD patients reported an increased rate of adverse events in the dual 5-aminosalicylates and azathioprine dual therapy group compared (48%) to the monotherapy azathioprine group (30%)(chi = 6.4, p = 0.05). Discontinuation of azathioprine because of adverse events was higher in the dual therapy group (52% vs. 24%).(5) In a prospective study, 16 Crohn's disease patients on a stable dose of azathioprine with sulfasalazine or mesalamine discontinued the aminosalicylate after 3 months, which resulted in an average decrease 0f 10% in 6-TGN levels. Myelosuppression may be related to increased levels of 6-TGN.(6) In a 8 week non-randomized parallel group drug interaction study, 34 patients with Crohn's disease receiving azathioprine or 6-mercaptopurine with mesalamine (4 g/day), or sulfasalazine (4 g/day), or balsalazide (6.75 g/day) had a high frequency of leukopenia (20-55%) and significant increases in whole blood 6-TGN levels.(7) A 16 year-old Crohn's disease patient on concurrent 6-mercaptopurine (75 mg) and olsalazine (1000 mg) developed leukopenia (WBC count 1.7 x 10*9/L, ANC 1.309 x 10*9/L, hemoglobulin 113 gm/L, platelet count 550 x 10*9/L) and required a dose reduction for 6-mercaptopurine. Another episode occurred later on after increasing her dose of olsalazine and 6-mercaptopurine which resulted in discontinuation of olsalazine.(8) An in vitro study showed that sulfasalazine and other aminosalicylate derivatives were able to inhibit recombinant human TPMT.(9) In a prospective study, 17 IBD patients on stable mercaptopurine and mesalamine therapy had a 23% reduction in 6-TGN levels after discontinuing mercaptopurine.(10)

Aspirin (> 100 Mg); Salicylates/Acetazolamide; Methazolamide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Acetazolamide and methazolamide may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system). Alternatively, toxicity may be due to salicylate-induced displacement of the carbonic anhydrase inhibitor from its protein binding sites and inhibition of renal tubular secretion.

CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur.

PREDISPOSING FACTORS: High doses of salicylates, low body weight.

PATIENT MANAGEMENT: Avoid the combination if possible. If it is necessary to administer these drugs concurrently, monitor salicylate levels and monitor the patient for symptoms of toxicity. Adjust the dose as needed.

DISCUSSION: Two young patients with unimpaired renal and hepatic function were found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of salicylates and carbonic anhydrase inhibitors in normal doses.(1) A 67-year old woman and a 75-year old woman taking carbonic anhydrase inhibitors for therapy of glaucoma and high doses of aspirin for arthritis developed severe acid-base imbalance and salicylate intoxication.(2) Neither patient exhibited ill effects when taking high aspirin doses without a carbonic anhydrase inhibitor. Carbonic anhydrase inhibitor-induced acidemia increases the risk of developing salicylate intoxication in patients receiving high aspirin doses. Two elderly patients, who were chronically receiving aspirin developed lethargy, incontinence, and confusion after dosing with acetazolamide.(3) These effects could have been due to either drug (see mechanism).

Aspirin (> 100 Mg); Salicylates/Antidiabetics, Oral

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Complex. Salicylates appear to have intrinsic glucose lowering properties via several proposed mechanisms. Also, salicylates may cause protein binding displacement of antidiabetics. Decreased renal clearance may also occur.

CLINICAL EFFECTS: Potentiation of hypoglycemic effects may be observed.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Hypoglycemic signs and blood glucose levels should be monitored. Adjust the antidiabetic dose as needed. Particular caution should be taken when salicylates are started or stopped in patients previously stabilized on antidiabetics.

DISCUSSION: Additional documentation is necessary to confirm this potential interaction.

Aspirin (>100 Mg); Salicylates/Uricosurics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Not clearly established. Protein binding displacement is a possibility.

CLINICAL EFFECTS: May observe hyperuricemia and gout resulting from reduced uricosuric response.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid chronic, moderate to high doses of salicylates.

DISCUSSION: This interaction is well documented. Occasional small doses of salicylates do not appear to inhibit the action of uricosurics.

Selected Salicylates/Heparin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Additive prolongation of bleeding time.

CLINICAL EFFECTS: Increased risk of bleeding which may extend for several days beyond discontinuation of salicylates.

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If this combination is used, monitor patients for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. A non-acetylated salicylate may be used to avoid antiplatelet activity. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Single ingredient aspirin or buffered aspirin products with strengths < or = 325 mg and combination aspirin products which are used to treat cardiovascular disease (e.g. aspirin+statins, aspirin+dipyridamole) are not included in this interaction.

DISCUSSION: This interaction is likely to occur.

Known hypersensitivity to salicylates, balsalazide, or its metabolites, or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• Disease of liver
• Kidney disease with reduction in glomerular filtration rate (GFr)

Adverse effects occurring in 4% or more of patients receiving balsalazide include headache, abdominal pain, diarrhea, nausea, vomiting, respiratory infection, arthralgia, flatulence, and fatigue.

Some adverse effects (e.g., abdominal pain, fatigue, nausea) appear to occur more frequently in women. The manufacturer states that certain adverse effects (e.g., abdominal pain, rectal bleeding, anemia) may be manifestations of ulcerative colitis.

Rare or Very Rare

• Abnormal hepatic function tests
• Acute generalized exanthematous pustulosis
• Acute hepatic failure
• Alveolitis
• DRESS syndrome
• Eosinophilic pneumonia
• Erythema nodosum
• Exacerbation of ulcerative colitis
• Gastroenteritis
• Hepatic cirrhosis
• Hepatocellular damage
• Hyperbilirubinemia
• Interstitial nephritis
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Kidney stone
• Myocarditis
• Obstructive hyperbilirubinemia
• Pancreatitis
• Pericarditis
• Pleural effusions
• Pleuritis
• Renal failure
• Stevens-johnson syndrome
• Toxic epidermal necrolysis
• Vasculitis

More Frequent

• Acute abdominal pain
• Anemia
• Diarrhea
• Headache disorder
• Nausea
• Pharyngitis
• Urinary tract infection

Less Frequent

• Anorexia
• Arthralgia
• Cough
• Dysmenorrhea
• Dyspepsia
• Fatigue
• Fever
• Flu-like symptoms
• Insomnia
• Musculoskeletal pain
• Rhinitis
• Sore throat
• Stomatitis

Rare or Very Rare

• Abdominal pain with cramps
• Alopecia
• Constipation
• Dizziness
• Dyspnea
• Facial edema
• Fecal urgency
• Flatulence
• Gastroesophageal reflux disease
• Hypertension
• Jaundice
• Lethargy
• Malaise
• Myalgia
• Pruritus of skin
• Skin rash
• Tachycardia
• Upper respiratory infection
• Vomiting
• Xerostomia

No enhanced messaging available.

Safety and efficacy not established in children younger than 18 years of age.

Category B. (See Users Guide.)

No enhanced messaging available.

Experience in those 65 years of age and older insufficient to determine whether they respond differently from younger adults.