Brimonidine/brinzolamide ophthalmic Disease Interactions

Sulfonamides may be systemically absorbed when applied to the skin, eye, or mucosal membranes. The use of sulfonamides has been associated with hematologic toxicity, including methemoglobinemia, sulfhemoglobinemia, leukopenia, granulocytopenia, eosinophilia, hemolytic anemia, aplastic anemia, purpura, clotting disorder, thrombocytopenia, hypofibrinogenemia, and hypoprothrombinemia. Therapy with topical sulfonamides should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Complete blood counts should be obtained regularly during prolonged therapy (>2 weeks), and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice.

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Sulfonamides may be systemically absorbed when applied to the skin, eye, or mucosal membranes. The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with topical sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.

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Sulfonamides may be systemically absorbed when applied to the skin, eye, or mucosal membranes. Therapy with topical sulfonamides should be administered cautiously in patients with porphyria, since these drugs can precipitate an acute attack. The use of oral sulfonamides is considered contraindicated in patients with porphyria.

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Topically applied alpha-2 adrenergic receptor agonists are systemically absorbed, with the potential for producing rare but clinically significant systemic effects. In the central nervous system, alpha adrenergic stimulation causes an inhibition of sympathetic vasomotor centers, resulting in decreased peripheral resistance and bradycardia. While the commercially available agents in the U.S. (apraclonidine and brimonidine) are hydrophilic and do not readily distribute across the ocular-blood barrier into the CNS, prolonged use may increase the risk of systemic effects. There have been occasional reports of bradycardia, chest heaviness or burning, palpitation, reduced blood pressure, and orthostatic hypotension when apraclonidine 1% was administered once or twice a day for 4 weeks to individuals not undergoing laser surgery. Therapy with ophthalmic alpha-2 adrenergic agents should be administered cautiously in patients with severe, uncontrolled cardiovascular disease, including hypertension, coronary or cerebrovascular insufficiency, recent myocardial infarction, chronic renal failure, Raynaud's disease, thromboangiitis obliterans, and a predisposition for orthostatic hypotension.

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Topically applied alpha-2 adrenergic receptor agonists are systemically absorbed, with the potential for producing rare but clinically significant systemic effects. Depression has infrequently been associated with the ocular use of these drugs due to their inhibiting effect on the sympathetic nervous system. Depressed patients should be monitored for exacerbation of their condition during therapy with ophthalmic alpha-2 adrenergic agents.

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Topically applied alpha-2 adrenergic receptor agonists are systemically absorbed, with the potential for producing rare but clinically significant systemic effects. There are limited data concerning the pharmacokinetic disposition or the clinical use of these drugs in patients with renal and/or liver disease. Therapy with ophthalmic alpha-2 adrenergic agents should be administered cautiously in patients with significantly impaired renal or hepatic function.

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Sulfonamides may be systemically absorbed when applied to the skin, eye, or mucosal membranes. The use of sulfonamides has been associated with crystalluria due to precipitation of the sulfonamide and/or its N4-acetyl metabolite in the urinary tract. Renal toxicity such as uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine has been reported. Hydration and adequate urinary output (> 1.5 L/day) should be maintained during sulfonamide administration. Patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk for the development of crystalluria and lithiasis and should be encouraged to consume additional amounts of liquid. Renal function tests and urinalysis should be performed regularly during prolonged therapy (> 2 weeks).

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Sulfonamides may be systemically absorbed when applied to the skin, eye, or mucosal membranes. Hepatotoxicity, including jaundice, diffuse hepatocellular necrosis, hypersensitivity hepatitis and hepatic failure, has rarely been reported in patients receiving sulfonamides. In addition, sulfonamides are partially metabolized by the liver and may accumulate in patients with hepatic impairment. Therapy with topical sulfonamides should be administered cautiously in patients with liver disease.

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Sulfonamides may be systemically absorbed when applied to the skin, eye, or mucosal membranes. Once absorbed, sulfonamides and their metabolites are eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from sulfonamides due to decreased drug clearance. Additionally, sulfonamides may cause renal toxicity secondary to crystalluria, including uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine. Hydration and adequate urinary output (> 1.5 L/day) should be maintained during sulfonamide administration. Renal function tests and urinalysis should be performed regularly during prolonged therapy (> 2 weeks). Some manufacturers of topical sulfonamide products do not recommend their use in patients with impaired renal function.

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Sulfonamides may be systemically absorbed when applied to the skin, eye, or mucosal membranes. Once absorbed, sulfonamides are excreted and concentrated in the urine. Therapy with topical sulfonamides should be administered cautiously in patients with urinary obstruction or retention, since excessive drug accumulation may occur. These patients may also be at increased risk for sulfonamide crystalluria, which may be associated with renal toxicity such as uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine. A urinary output of at least 1.5 L/day should be maintained during sulfonamide administration. Renal function tests and urinalysis should be performed regularly during prolonged therapy (> 2 weeks).

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