Brimonidine/dorzolamide/latanoprost/timolol ophthalmic Disease Interactions

Latanoprost should be used with caution in patients with a history of herpetic keratitis and it should be avoided in cases of active simplex keratitis because of the risk of reactivation and inflammation.

Ophthalmic beta-adrenergic receptor blocking agents (aka beta-blockers) in general should not be used in patients with a current or past history of bronchial asthma or chronic obstructive pulmonary disease. Topically applied beta-blockers are systemically absorbed, with the potential for producing clinically significant systemic effects even at low or undetectable plasma levels. In the respiratory tract, beta blockade may adversely affect pulmonary function by counteracting the bronchodilation produced by catecholamine stimulation of beta-2 receptors. Although agents with beta-1 selectivity (e.g., betaxolol) are considered safer in patients with bronchospastic diseases, cardioselectivity is not absolute and may be lost with larger doses or higher plasma levels.

The use of ophthalmic beta-adrenergic receptor blocking agents (aka beta-blockers) is considered by manufacturers to be contraindicated in patients with sinus bradyarrhythmia or heart block greater than the first degree (unless a functioning pacemaker is present). Topically applied beta-blockers are systemically absorbed, with the potential for producing clinically significant systemic effects even at low or undetectable plasma levels. In cardiac tissues, beta blockade causes a reduction in inotropic as well as chronotropic activity, which may further depress cardiac function in such patients.

The use of ophthalmic beta-adrenergic receptor blocking agents (aka beta-blockers) is considered by manufacturers to be contraindicated in patients with cardiogenic shock. Topically applied beta-blockers are systemically absorbed, with the potential for producing clinically significant systemic effects even at low or undetectable plasma levels. In cardiac tissues, beta blockade causes a reduction in inotropic as well as chronotropic activity, which may further depress cardiac output and blood pressure in such patients.

The use of ophthalmic beta-adrenergic receptor blocking agents (aka beta-blockers) is considered by manufacturers to be contraindicated in patients with overt congestive heart failure (CHF). Topically applied beta-blockers are systemically absorbed, with the potential for producing clinically significant systemic effects even at low or undetectable plasma levels. Since sympathetic stimulation may be important in maintaining the hemodynamic function in patients with CHF, beta blockade can worsen the heart failure. However, therapy with ophthalmic beta-blockers can be administered cautiously in some CHF patients provided they are well compensated and receiving digitalis, diuretics, an ACE inhibitor, and/or nitrates. Beta-blockers should be discontinued if cardiac failure develops or worsens during therapy.

Beta-adrenergic receptor blocking agents (aka beta-blockers) may mask symptoms of hypoglycemia such as tremors, tachycardia and blood pressure changes. In addition, the nonselective beta-blockers (e.g., timolol, carteolol) may inhibit catecholamine-mediated glycogenolysis, thereby potentiating insulin-induced hypoglycemia and delaying the recovery of normal blood glucose levels. Since topically applied beta-blockers are systemically absorbed and may produce clinically significant systemic effects even at low or undetectable plasma levels, therapy with ophthalmic beta-blockers should be administered cautiously in patients with diabetes or predisposed to spontaneous hypoglycemia.

Topically applied beta-adrenergic receptor blocking agents (aka beta-blockers) are systemically absorbed, with the potential for producing clinically significant systemic effects even at low or undetectable plasma levels. The use of beta-blockers in patients with a history of allergic reactions or anaphylaxis may be associated with heightened reactivity to culprit allergens. The frequency and/or severity of attacks may be increased during beta-blocker therapy. In addition, these patients may be refractory to the usual doses of epinephrine used to treat acute hypersensitivity reactions and may require a beta-agonist such as isoproterenol.

Beta-adrenergic receptor blocking agents (aka beta-blockers) may mask some symptoms of hyperthyroidism such as tachycardia, anxiety, tremor, and heat intolerance. Abrupt withdrawal of beta-blocker therapy in thyrotoxic patients may exacerbate symptoms of hyperthyroidism or precipitate a thyroid storm. Since topically applied beta-blockers are systemically absorbed and may produce clinically significant systemic effects even at low or undetectable plasma levels, therapy with ophthalmic beta-blockers should be administered cautiously in patients with or suspected of having hyperthyroidism. Cessation of beta-blocker therapy, when necessary, should occur gradually over a period of 1 to 2 weeks. Patients should be advised not to discontinue treatment without first consulting with the physician. Close monitoring is recommended during and after therapy withdrawal.

Due to their negative inotropic and chronotropic effects on the heart, beta-adrenergic receptor blocking agents (aka beta-blockers) reduce cardiac output and may precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. In addition, the nonselective beta-blockers (e.g., timolol, carteolol) may attenuate catecholamine-mediated vasodilation during exercise by blocking beta-2 receptors in peripheral vessels. Since topically applied beta-blockers are systemically absorbed and may produce clinically significant systemic effects even at low or undetectable plasma levels, therapy with ophthalmic beta-blockers should be administered cautiously in patients with peripheral vascular disease. Close monitoring for progression of arterial obstruction is advised.

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.

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.

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.

Latanoprost should be used with caution in patients with respiratory disorders as there have been reported post marketing cases of asthma and exacerbation of asthma, and dyspnea.

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.

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.

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.

Topically applied beta-adrenergic receptor blocking agents (aka beta-blockers) are systemically absorbed, with the potential for producing clinically significant systemic effects even at low or undetectable plasma levels. In the nervous and musculoskeletal systems, beta blockade may potentiate muscle weakness consistent with certain myasthenic symptoms such as diplopia, ptosis, and generalized weakness. Several beta-blockers have been associated rarely with aggravation of muscle weakness in patients with preexisting myasthenia gravis or myasthenic symptoms.

Macular edema, including cystoid macular edema, has been reported during treatment with ophthalmic prostaglandin analogues. Most cases occurred in patients with aphakia, pseudophakia with a torn posterior lens capsule, or known risk factors for macular edema (e.g., posterior uveitis, certain retinal disorders). Therapy with ophthalmic prostaglandin analogues should be administered cautiously in these patients.

Bimatoprost, latanoprost, and travoprost are synthetic prostaglandin analogues. Theoretically, these agents may mimic endogenous prostaglandins and mediate ocular inflammatory responses. In clinical trials, uveitis and iritis have been reported rarely. Therapy with ophthalmic prostaglandin analogues should be administered cautiously in patients with active intraocular inflammation.

Prostaglandin F2-alpha analogues are hydrolyzed by esterases in the cornea to their corresponding active free acid form, which is absorbed systemically and metabolized by the liver via fatty acid beta-oxidation, then eliminated by the kidney. These agents have not been adequately studied in the treatment of patients with impaired renal and/or hepatic function. Therapy with ophthalmic prostaglandin F2-alpha analogues should be administered cautiously in such patients.

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).

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.

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.

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).