Drug Interactions between Ana-Kit and timolol ophthalmic
This report displays the potential drug interactions for the following 2 drugs:
- Ana-Kit (chlorpheniramine/epinephrine)
- timolol ophthalmic
Interactions between your drugs
EPINEPHrine timolol ophthalmic
Applies to: Ana-Kit (chlorpheniramine / epinephrine) and timolol ophthalmic
MONITOR CLOSELY: Noncardioselective beta-blockers can significantly enhance the pressor response to epinephrine. The mechanism involves blockade of beta-2 adrenergic receptors in the peripheral vasculature, resulting in unopposed alpha-adrenergic effect of epinephrine that is responsible for vasoconstriction. Severe hypertension accompanied by bradycardia has been reported in patients who were treated with a noncardioselective beta-blocker like propranolol or nadolol prior to receiving epinephrine. In rare cases, cardiac arrest and stroke have occurred. This interaction has not been reported with cardioselective beta-blockers, which generally have little effect on beta-2 adrenergic receptors at therapeutic dosages. In studies of hypertensive patients, treatment with propranolol was associated with significant increases in blood pressure and peripheral vascular resistance and decreases in heart rate and forearm blood flow in response to epinephrine administration, while metoprolol had only minor effects on epinephrine-induced cardiovascular changes compared to placebo. Similarly, in 24 healthy subjects treated with nadolol, atenolol, or placebo for one week prior to epinephrine administration, mean arterial pressure and calf vascular resistance increased significantly in the nadolol group but not in the atenolol group, and marked bradycardia also occurred in the former but not latter group. Theoretically, the interaction may also occur with noncardioselective beta-blocker ophthalmic preparations, since they may be systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.
MONITOR CLOSELY: Beta-blockers may attenuate the response to epinephrine in the treatment of anaphylactic reactions. Noncardioselective beta-blockers, in particular, can antagonize the bronchodilating effects of epinephrine by blocking beta-2 adrenergic receptors in smooth muscles of the bronchial tree. All beta-blockers can antagonize the cardiostimulatory effects of epinephrine by blocking beta-1 adrenergic receptors in the heart. Some investigators have suggested that the use of beta-blockers in itself is associated with an increased incidence and severity of anaphylaxis due to modulation of adenylate cyclase, which can influence release of anaphylactogenic mediators. However, data are limited and conflicting.
MANAGEMENT: Extreme caution and close monitoring of cardiovascular status are indicated when epinephrine is administered to patients treated with noncardioselective beta-blockers. A dosage reduction of epinephrine may be necessary. Withdrawal of beta-blockers before anesthesia may increase the risk of myocardial ischemia and is not recommended. The interaction is not expected to occur with local anesthetics used in dental surgery that contain very low concentrations of epinephrine.
References
- Whelan TV (1987) "Propranolol, epinephrine, and accelerated hypertension during hemodialysis." Ann Intern Med, 106, p. 327
- Gandy W (1989) "Severe epinephrine-propanolol interaction." Ann Emerg Med, 18, p. 98-9
- van Herwaarden CL, Binkhorst RA, Fennis JF, van 't Laar A (1977) "Effects of adrenaline during treatment with propranolol and metoprolol." Br Med J, 2, p. 1029
- Houben H, Thien TH, De Boo TH, et al. (1979) "Influence of selective and non-selective beta-adrenoceptor blockade on the haemodynamic effect of adrenaline during combined antihypertensive drug therapy." Clin Sci, 57, s397-9
- van Herwaarden CL, Fennis JF, Binkhorst RA, van 't Laar A (1977) "Haemodynamic effects of adrenaline during treatment of hypertensive patients with propranolol and metoprolol." Eur J Clin Pharmacol, 12, p. 397-402
- Hansbrough JF, Near A (1980) "Propranolol-epinephrine antagonism with hypertension and stroke." Ann Intern Med, 92, p. 717
- Cryer PE, Rizza RA, Haymond MW, Gerich JE (1980) "Epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man." Metabolism, 29, p. 1114-8
- Saff R, Nahhas A, Fink JN (1993) "Myocardial infarction induced by coronary vasospasm after self- administration of epinephrine." Ann Allergy, 70, p. 396-8
- Larsen LS, Larsen A (1990) "Labetalol in the treatment of epinephrine overdose." Ann Emerg Med, 19, p. 680-2
- Catalano PM (1984) "Possible interaction of epinephrine with propranolol." J Am Acad Dermatol, 10, p. 839
- Spencer PS, Klein LE (1986) "Interaction of epinephrine and propranolol." J Am Acad Dermatol, 14, p. 1093-4
- Foster CA, Aston SJ (1983) "Propranolol-epinephrine interaction: a potential disaster." Plast Reconstr Surg, 72, p. 74-8
- Greenwald AE (1983) "Propranolol-epinephrine interaction." J Dermatol Surg Oncol, 9, p. 713
- Goldberg I, Ashburn FS Jr, Palmberg PF, Kass MA, Becker B (1980) "Timolol and epinephrine: a clinical study of ocular interactions." Arch Ophthalmol, 98, p. 484-6
- Alexander GD (1985) "Dangers of propranolol withdrawal prior to local anesthesia with epinephrine." Arch Otolaryngol, 111, p. 280
- Reeves RA, Boer WH, DeLeve L, Leenen FH (1984) "Nonselective beta-blockade enhances pressor responsiveness to epinephrine, norepinephrine, and angiotensin II in normal man." Clin Pharmacol Ther, 35, p. 461-6
- Dzubow LM (1986) "The interaction between propranolol and epinephrine as observed in patients undergoing Mohs' surgery." J Am Acad Dermatol, 15, p. 71-5
- Richards DA, Prichard BN, Hernandez R (1979) "Circulatory effects of noradrenaline and adrenaline before and after labetalol." Br J Clin Pharmacol, 7, p. 371-8
- Halloran TJ, Phillips CE (1981) "Propranolol intoxication. A severe case responding to norepinephrine therapy." Arch Intern Med, 141, p. 810-1
- Chu D, Cocco G, Schweda E, Haeusler G, Strozzi C (1980) "Influence of propranolol and pindolol on the haemodynamic effects of papaverine, isoprenaline and noradrenaline in hypertensive patients." Eur J Clin Pharmacol, 18, p. 141-6
- O'Grady J, Oh V, Turner P (1978) "Effects of propranolol and oxprenolol on the vasoconstrictor response to noradrenaline in the superficial hand vein in man." Eur J Clin Pharmacol, 14, p. 83-5
- Fisher DA (1995) "Interaction of epinephrine and B-blockers." JAMA, 274, p. 1830
- Jay GT, Chow MS (1995) "Interaction of epinephrine and B-blockers." JAMA, 274, p. 1830-1
- Ponten J, Biber B, Bjuro T, Henriksson BA, Hjalmarson A, Lundberg D (1982) "Beta-receptor blockade and spinal anaesthesia. Withdrawal versus continuation of long-term therapy." Acta Anaesthesiol Scand Suppl, 76, p. 62-9
- Centeno RF, Yu YL (2003) "The propanolol-epinephrine interaction revisited: a serious and potentially catastrophic adverse drug interaction in facial plastic surgery." Plast Reconstr Surg, 111, p. 944-5
chlorpheniramine timolol ophthalmic
Applies to: Ana-Kit (chlorpheniramine / epinephrine) and timolol ophthalmic
MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the systemic effects of topically administered timolol, which is metabolized by the isoenzyme. Following ocular administration, timolol is systemically absorbed and can reach plasma levels associated with adverse beta-adrenergic blocking effects such as bronchospasm, depression, bradycardia, and hypotension. The risk may be increased if clearance of the drug is significantly diminished by concomitant CYP450 2D6 inhibitors. In one case report, a 70-year-old man experienced dizziness secondary to sinus bradycardia after 12 weeks of treatment with a 0.5% timolol eye drop while also taking quinidine sulfate 500 mg three times a day. The symptoms subsided and sinus rhythm returned to normal a day after discontinuation of both drugs. However, symptoms returned within 30 hours after restarting both drugs a month later. Quinidine was discontinued, and the patient did not experience further problems. In a study of 13 healthy volunteers, extensive metabolizers of CYP450 2D6 administered quinidine (50 mg single oral dose) 30 minutes before 0.5% timolol eye drop (2 drops in each nostril) demonstrated significantly greater reductions in exercise heart rate and had higher plasma timolol concentrations than when given timolol alone. The changes resulted in values that were similar to those observed in poor metabolizers given the timolol eye drop without quinidine. In another study, 12 healthy volunteers given cimetidine (400 mg orally twice a day for 7 doses) and 0.5% timolol eye drop (0.05 mL in each eye 30 minutes after last dose of cimetidine) demonstrated additional reductions in resting heart rate and intraocular pressure relative to administration of the timolol eye drop alone, although there were no additional reductions of exercise heart rate or systolic blood pressure (at rest or after exercise) compared to timolol alone.
MANAGEMENT: Patients should be monitored for systemic beta-adrenergic blocking effects of topical timolol during coadministration with CYP450 2D6 inhibitors such as cimetidine, quinidine, and certain selective serotonin reuptake inhibitors. Particular caution is warranted in elderly patients, since they are generally more susceptible to adverse effects of topically administered beta blockers.
References
- Dinai Y, Sharir M, Floman NN, Halkin H (1985) "Bradycardia induced by interaction between quinidine and ophthalmic timolol." Ann Intern Med, 103, p. 890-1
- Lewis RV, Lennard MS, Jackson PR, Tucker GT, Ramsay LE, Woods HF (1985) "Timolol and atenolol: relationships between oxidation phenotype, pharmacokinetics and pharmacodynamics." Br J Clin Pharmacol, 19, p. 329-33
- Alvan G, Calissendorff B, Seideman P, Widmark K, Widmark G (1980) "Absorption of ocular timolol." Clin Pharmacokinet, 5, p. 95-100
- Edeki TI, He HB, Wood AJJ (1995) "Pharmacogenetic explanation for excessive beta-blockade following timolol eye drops: potential for oral-ophthalmic drug interaction." JAMA, 274, p. 1611-3
- Higginbotham E (1996) "Topical beta-adrenergic antagonists and quinidine: a risky interaction." Arch Ophthalmol, 114, p. 745-6
- Ishii Y, Nakamura K, Tsutsumi K, Kotegawa T, Nakano S, Nakatsuka K (2000) "Drug interaction between cimetidine and timolol ophthalmic solution: Effect on heart rate and intraocular pressure in healthy Japanese volunteers." J Clin Pharmacol, 40, p. 193-9
- Fraunfelder FT, Fraunfelder FW; Randall JA (2001) "Drug-Induced Ocular Side Effects" Boston, MA: Butterworth-Heinemann
Drug and food interactions
chlorpheniramine food
Applies to: Ana-Kit (chlorpheniramine / epinephrine)
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
EPINEPHrine food
Applies to: Ana-Kit (chlorpheniramine / epinephrine)
MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.
MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.
References
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
- Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
- (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
- (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
- (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
- (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
- (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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