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Drug Interactions between brimonidine / timolol ophthalmic and Theolate

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

theophylline timolol ophthalmic

Applies to: Theolate (guaifenesin / theophylline) and brimonidine / timolol ophthalmic

GENERALLY AVOID: The pharmacologic effects of theophyllines and beta-blockers are opposite. Nonselective and high doses of cardioselective beta-blockers may cause severe or fatal bronchospasm by opposing theophylline-induced bronchodilation. Ophthalmic beta-blockers undergo significant systemic absorption and may also interact. In addition, propranolol and other beta-blockers may reduce the CYP450 hepatic metabolism of theophylline, and serum theophylline levels may be increased.

MANAGEMENT: Oral and ophthalmic nonselective beta-blockers (e.g., carteolol, carvedilol, levobunolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, and timolol) are considered contraindicated in patients with bronchospastic diseases. Cardioselective beta-blockers should generally be avoided, or used with extreme caution if no other alternatives are available and the benefits outweigh the risks of potentially severe bronchospasm. If patients do receive this combination, they should be closely monitored for increased serum theophylline levels but decreased bronchodilatory effectiveness.

References

  1. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part II)." Clin Pharmacokinet 20 (1991): 135-50
  2. Conrad KA, Nyman DW "Effects of metoprolol and propranolol on theophylline elimination." Clin Pharmacol Ther 28 (1980): 463-7
  3. Horvath JS, Woolcock AJ, Tiller DJ, Donnelly P, Armstrong J, Caterson R "A comparison of metoprolol and propranolol on blood pressure and respiratory function in patients with hypertension." Aust N Z J Med 8 (1978): 1-6
  4. Mue S, Sasaki T, Shibahara S, et al. "Influence of metoprolol on hemodynamics and respiratory function in asthmatic patients." Int J Clin Pharmacol Biopharm 17 (1979): 346-50
  5. Lombardi TP, Bertino JS, Goldberg A, Middleton E, Slaughter RL "The effects of a beta-2 selective adrenergic agonist and a beta- nonselective antagonist on theophylline clearance." J Clin Pharmacol 27 (1987): 523-9
View all 5 references

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Moderate

timolol ophthalmic brimonidine ophthalmic

Applies to: brimonidine / timolol ophthalmic and brimonidine / timolol ophthalmic

MONITOR: Topically administered alpha-2 adrenergic receptor agonists such as apraclonidine and brimonidine are systemically absorbed, with the potential for producing rare but clinically significant systemic effects such as hypotension and bradycardia. The possibility for an additive or potentiating effect on blood pressure and heart rate should be considered when used with other medications that affect these parameters, such as ophthalmic and systemic beta blockers, vasodilators, cardiac glycosides, and antihypertensive agents.

MANAGEMENT: Blood pressure and pulse rate should be monitored regularly when topical alpha-2 adrenergic receptor agonists are prescribed in combination with cardiovascular drugs. Patients should be advised to notify their physician if they experience slow pulse, irregular heartbeat, dizziness, lightheadedness, or syncope.

References

  1. King MH, Richards DW "Near syncope and chest tightness after administration of apraclonidine before argon laser iridotomy." Am J Ophthalmol 110 (1990): 308-9
  2. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc PROD
  3. Nordlund JR, Pasquale LR, Robin AL, Rudikoff MT, Ordman J, Chen KS, Walt J "The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine." Arch Ophthalmol 113 (1995): 77-83
  4. "Product Information. Alphagan (brimonidine ophthalmic)." Allergan Inc PROD (2001):
  5. Walters TR "Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies." Surv Ophthalmol 41 ( Suppl (1996): s19-26
  6. Pekdemir M, Yanturali S, Karakus G "More than just an ocular solution." Emerg Med J 22 (2005): 753-4
  7. "Product Information. Mirvaso (brimonidine topical)." Galderma Laboratories Inc (2013):
View all 7 references

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Drug and food interactions

Moderate

theophylline food

Applies to: Theolate (guaifenesin / theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

theophylline food

Applies to: Theolate (guaifenesin / theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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