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Drug Interaction Report

6 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

aspirin dorzolamide ophthalmic

Applies to: Panasal 5/500 (aspirin / hydrocodone), brimonidine / dorzolamide / timolol ophthalmic

GENERALLY AVOID: The combination of large doses of salicylates and oral carbonic anhydrase inhibitors (CAI) may rarely result in severe metabolic acidosis and/or salicylate toxicity. The mechanism is unknown but may involve salicylate-induced displacement of CAIs from plasma protein-binding sites and reduced renal clearance, or CAI-induced plasma pH changes resulting in increased amounts of unionised salicylates entering the CNS. Coma and death have been reported. Although this has not been reported with ocular CAIs, the clinician should consider the possibility of an interaction with these agents, also.

MANAGEMENT: In general, concomitant use of antirheumatic doses of salicylates and oral CAIs is not recommended. If coadministration is necessary, careful monitoring of the patient's mental status and acid base balance is strongly recommended. Patients should be advised to promptly notify their physicians if they experience symptoms such as lethargy, tinnitus, confusion, nausea, vomiting, or hyperventilation.

References

  1. Sweeney KR, Chapron DJ, Kramer PA (1988) "Effect of salicylate on serum protein binding and red blood cell uptake of acetazolamide in vitro." J Pharm Sci, 77, p. 751-6
  2. Favre L, Vallotton MB (1984) "Relationship of renal prostaglandins to three diuretics." Prostaglandins Leukot Med, 14, p. 313-9
  3. Cowan RA, Hartnell GG, Lowdell CP, Baird IM, Leak AM (1984) "Metabolic acidosis induced by carbonic anhydrase inhibitors and salicylates in patients with normal renal function." Br Med J (Clin Res Ed), 289, p. 347-8
  4. Sweeney KR, Chapron DJ, Brandt JL, Gomolin IH, Feig PU, Kramer PA (1986) "Toxic interaction between acetazolamide and salicylate: case reports and a pharmacokinetic explanation." Clin Pharmacol Ther, 40, p. 518-24
  5. Anderson CJ, Kaufman PL, Sturm RJ (1978) "Toxicity of combined therapy with carbonic anhydrase inhibitors and aspirin." Am J Ophthalmol, 86, p. 516-9
  6. Sweeney KR, Chapron DJ, Antal EJ, Kramer PA (1989) "Differential effects of flurbiprofen and aspirin on acetazolamide disposition in humans." Br J Clin Pharmacol, 27, p. 866-9
  7. Rousseau P, Fuentevilla-Clifton A (1993) "Acetazolamide and salicylate interaction in the elderly: a case report." J Am Geriatr Soc, 41, p. 868-9
  8. (2001) "Product Information. Diamox (acetazolamide)." Lederle Laboratories
  9. (2001) "Product Information. Azopt (brinzolamide ophthalmic)." Alcon Laboratories Inc
  10. (2001) "Product Information. Trusopt (dorzolamide ophthalmic)." Merck & Co., Inc
  11. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  12. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  13. Cerner Multum, Inc. "Australian Product Information."
View all 13 references

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Moderate

HYDROcodone brimonidine ophthalmic

Applies to: Panasal 5/500 (aspirin / hydrocodone), brimonidine / dorzolamide / 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. Although the interaction has not been specifically studied, the possibility of an additive or potentiating effect with central nervous system (CNS) depressants such as alcohol, barbiturates, opiates, anxiolytics, sedatives, and anesthetics should be considered. Additive hypotensive effects and orthostasis may also occur with some CNS depressants and other agents that have these effects, particularly during initial dosing and/or parenteral administration.

MANAGEMENT: Patients receiving topical alpha-2 adrenergic receptor agonists in combination with agents that can cause CNS depression should be made aware of the potential for increased adverse effects such as drowsiness, dizziness, lightheadedness and confusion, and counseled to avoid activities requiring mental alertness until they know how these agents affect them. Patients should also avoid rising abruptly from a sitting or recumbent position and notify their physician if they experience orthostasis or tachycardia.

References

  1. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
  2. (2001) "Product Information. Alphagan (brimonidine ophthalmic)." Allergan Inc
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Pekdemir M, Yanturali S, Karakus G (2005) "More than just an ocular solution." Emerg Med J, 22, p. 753-4
  5. (2013) "Product Information. Mirvaso (brimonidine topical)." Galderma Laboratories Inc
View all 5 references

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Moderate

timolol ophthalmic brimonidine ophthalmic

Applies to: brimonidine / dorzolamide / timolol ophthalmic, brimonidine / dorzolamide / 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 (1990) "Near syncope and chest tightness after administration of apraclonidine before argon laser iridotomy." Am J Ophthalmol, 110, p. 308-9
  2. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
  3. Nordlund JR, Pasquale LR, Robin AL, Rudikoff MT, Ordman J, Chen KS, Walt J (1995) "The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine." Arch Ophthalmol, 113, p. 77-83
  4. (2001) "Product Information. Alphagan (brimonidine ophthalmic)." Allergan Inc
  5. Walters TR (1996) "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, s19-26
  6. Pekdemir M, Yanturali S, Karakus G (2005) "More than just an ocular solution." Emerg Med J, 22, p. 753-4
  7. (2013) "Product Information. Mirvaso (brimonidine topical)." Galderma Laboratories Inc
View all 7 references

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Drug and food interactions

Major

HYDROcodone food

Applies to: Panasal 5/500 (aspirin / hydrocodone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

References

  1. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc

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Moderate

aspirin food

Applies to: Panasal 5/500 (aspirin / hydrocodone)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Minor

aspirin food

Applies to: Panasal 5/500 (aspirin / hydrocodone)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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Therapeutic duplication warnings

No duplication 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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.