Drug Interactions between betaxolol and MLK F2
This report displays the potential drug interactions for the following 2 drugs:
- betaxolol
- MLK F2 (bupivacaine/lidocaine/triamcinolone)
Interactions between your drugs
lidocaine BUPivacaine
Applies to: MLK F2 (bupivacaine / lidocaine / triamcinolone) and MLK F2 (bupivacaine / lidocaine / triamcinolone)
GENERALLY AVOID: Additive toxicities may occur when bupivacaine is coadministered with other local anesthetics. The potential for increased risk of systemic toxicities such as methemoglobinemia and central nervous system and cardiovascular adverse reactions should be recognized.
MANAGEMENT: Additional use of local anesthetics should generally be avoided within 96 hours following administration of bupivacaine. If coadministration cannot be avoided, overall local anesthetic exposure through 72 hours must be considered in addition to monitoring for the development of methemoglobinemia as well as central nervous system and cardiovascular adverse reactions. Signs and symptoms of methemoglobinemia may be delayed some hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia such as slate-grey cyanosis in buccal mucous membranes, lips, and nail beds; nausea; headache; dizziness; lightheadedness; lethargy; fatigue; dyspnea; tachypnea; tachycardia; palpitation; anxiety; and confusion. In severe cases, patients may progress to central nervous system depression, stupor, seizures, acidosis, cardiac arrhythmias, syncope, shock, coma, and death. Early warning signs of central nervous system toxicity may include restlessness, anxiety, incoherent speech, dizziness, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, blurred vision, tremors, twitching, depression, and drowsiness. Cardiovascular toxicity may include atrioventricular block, ventricular arrhythmias, cardiac arrest, and decreased cardiac output and arterial blood pressure due to depressed cardiac conductivity, excitability, and myocardial contractility. Patients should have cardiovascular and respiratory vital signs and state of consciousness constantly monitored while under treatment.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2021) "Product Information. Zynrelef (bupivacaine-meloxicam)." Heron Therapeutics
lidocaine betaxolol
Applies to: MLK F2 (bupivacaine / lidocaine / triamcinolone) and betaxolol
MONITOR: Some beta-blockers may increase lidocaine levels and risk of toxicity. The proposed mechanism is enzyme inhibition and/or decreased cardiac output and hepatic blood flow resulting in decreased hepatic metabolism of lidocaine. In addition beta-blockers and lidocaine may also have additive negative inotropic effects on the heart. Data have been conflicting and variable.
MANAGEMENT: Patients receiving concurrent therapy should be monitored for drowsiness, mental status changes, bradycardia, and hypotension. Lidocaine levels should be obtained when clinically necessary. If toxicity is suspected, the lidocaine infusion should be decreased, as possible.
References
- Miners JO, Wing MH, Lillywhite KJ, Smith KJ (1984) "Failure of "therapeutic" doses of beta-adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine." Br J Clin Pharmacol, 18, p. 853-60
- Ochs HR, Carstens G, Greenblatt DJ (1980) "Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol." N Engl J Med, 303, p. 373-7
- Schneck DW, Luderer JR, Davis D, Vary J (1984) "Effects of nadolol and propranolol on plasma lidocaine clearance." Clin Pharmacol Ther, 36, p. 584-7
- Svendsen TL, Tango M, Waldorff S, et al. (1982) "Effects of propranolol and pindolol on plasma lignocaine clearance in man." Br J Clin Pharmacol, 13, s223-6
- Conrad KA, Byers JM, Finley PR, Burnham L (1983) "Lidocaine elimination: effects of metoprolol and of propranolol." Clin Pharmacol Ther, 33, p. 133-8
- Jordo L, Johnsson G, Lundborg P, Regardh CG (1984) "Pharmacokinetics of lidocaine in healthy individuals pretreated with multiple doses of metoprolol." Int J Clin Pharmacol Ther Toxicol, 22, p. 312-5
- Graham CF, Turner WM, Jones JK (1981) "Lidocaine-propranolol interactions ." N Engl J Med, 304, p. 1301
- Ochs HR, Skanderra D, Abernethy DR, Greenblatt DJ (1983) "Effect of penbutolol on lidocaine kinetics." Arzneimittelforschung, 33, p. 1680-1
- Bax ND, Tucker GT, Lennard MS, Woods HF (1985) "The impairment of lignocaine clearance by propranolol: major contribution from enzyme inhibition." Br J Clin Pharmacol, 19, p. 597-603
- Parker G, Ene MD, Daneshmend TK, Roberts CJ (1984) "Do beta blockers differ in their effects on hepatic microsomal enzymes and liver blood flow?" J Clin Pharmacol, 24, p. 493-9
betaxolol BUPivacaine
Applies to: betaxolol and MLK F2 (bupivacaine / lidocaine / triamcinolone)
MONITOR: Beta-blockers may increase the risk of bupivacaine-induced side effects. The proposed mechanism is increased bupivacaine levels due to hepatic enzyme inhibition (propranolol) and/or additive negative inotropic effects on the heart. Patients with heart failure may be at a greater risk. Data have been conflicting and variable. Theoretically, beta-blocker ophthalmic solutions may also interact, as they are systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.
MANAGEMENT: Caution is recommended if multiple doses of bupivacaine are administered in the presence of a beta-blocker. Monitoring for drowsiness, mental status changes, convulsions, ECG changes, and hypotension is advisable during concurrent therapy.
References
- Roitman K, Sprung J, Wallace M, Matjasko J (1993) "Enhancement of bupivacaine cardiotoxcity with cardiac glycosides and beta-adrenergic blockers: a case report." Anesth Analg, 76, p. 658-61
- 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
- Ponten J, Biber B, Henriksson BA, Jonsteg C (1982) "Bupivacaine for intercostal nerve blockade in patients on long-term beta-receptor blocking therapy." Acta Anaesthesiol Scand Suppl, 76, p. 70-7
betaxolol triamcinolone
Applies to: betaxolol and MLK F2 (bupivacaine / lidocaine / triamcinolone)
MONITOR: Corticosteroids may antagonize the effects of antihypertensive medications by inducing sodium and fluid retention. These effects may be more common with the natural corticosteroids (cortisone, hydrocortisone) because they have greater mineralocorticoid activity. Conversely, some calcium channel blockers such as diltiazem and verapamil may increase corticosteroid plasma levels and effects by inhibiting their clearance via CYP450 3A4 metabolism.
MANAGEMENT: Patients on prolonged (i.e., longer than about a week) or high-dose corticosteroid therapy should have blood pressure, electrolyte levels, and body weight monitored regularly, and be observed for the development of edema and congestive heart failure. The dosages of antihypertensive medications may require adjustment.
References
- "Multum Information Services, Inc. Expert Review Panel"
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
Drug and food interactions
lidocaine food
Applies to: MLK F2 (bupivacaine / lidocaine / triamcinolone)
MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of lidocaine, which is primarily metabolized by the CYP450 3A4 and 1A2 isoenzymes to active metabolites (monoethylglycinexylidide (MEGX) and glycinexylidide). The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported with oral and/or intravenous lidocaine and potent CYP450 3A4 inhibitor, itraconazole, as well as moderate CYP450 3A4 inhibitor, erythromycin. A pharmacokinetic study of 9 healthy volunteers showed that the administration of lidocaine oral (1 mg/kg single dose) with itraconazole (200 mg daily) increased lidocaine systemic exposure (AUC) and peak plasma concentration (Cmax) by 75% and 55%, respectively. However, no changes were observed in the pharmacokinetics of the active metabolite MEGX. In the same study, when the moderate CYP450 3A4 inhibitor erythromycin (500 mg three times a day) was administered, lidocaine AUC and Cmax increased by 60% and 40%, respectively. By contrast, when intravenous lidocaine (1.5 mg/kg infusion over 60 minutes) was administered on the fourth day of treatment with itraconazole (200 mg once a day) no changes in lidocaine AUC or Cmax were observed. However, when lidocaine (1.5 mg/kg infusion over 60 minutes) was coadministered with erythromycin (500 mg three times a day) in the same study, the AUC and Cmax of the active metabolite MEGX significantly increased by 45-60% and 40%, respectively. The observed differences between oral and intravenous lidocaine when coadministered with CYP450 3A4 inhibitors may be attributed to inhibition of CYP450 3A4 in both the gastrointestinal tract and liver affecting oral lidocaine to a greater extent than intravenous lidocaine. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. While the clinical significance of this interaction is unknown, increased exposure to lidocaine may lead to serious and/or life-threatening reactions including respiratory depression, convulsions, bradycardia, hypotension, arrhythmias, and cardiovascular collapse.
MONITOR: Certain foods and behaviors that induce CYP450 1A2 may reduce the plasma concentrations of lidocaine. The proposed mechanism is induction of hepatic CYP450 1A2, one of the isoenzymes responsible for the metabolic clearance of lidocaine. Cigarette smoking is known to be a CYP450 1A2 inducer. In one pharmacokinetic study of 4 smokers and 5 non-smokers who received 2 doses of lidocaine (100 mg IV followed by 100 mg orally after a 2-day washout period), the smokers' systemic exposure (AUC) of oral lidocaine was 68% lower than non-smokers. The AUC of IV lidocaine was only 9% lower in smokers compared with non-smokers. Other CYP450 1A2 inducers include cruciferous vegetables (e.g., broccoli, brussels sprouts) and char-grilled meat. Therefore, eating large or variable amounts of these foods could also reduce lidocaine exposure. The clinical impact of smoking and/or the ingestion of foods that induce CYP450 1A2 on lidocaine have not been studied, however, a loss of efficacy may occur.
MANAGEMENT: Caution is recommended if lidocaine is to be used in combination with grapefruit and grapefruit juice. Monitoring for lidocaine toxicity and plasma lidocaine levels may also be advised, and the lidocaine dosage adjusted as necessary. Patients who smoke and/or consume cruciferous vegetables may be monitored for reduced lidocaine efficacy.
References
- Huet PM, LeLorier J (1980) "Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics" Clin Pharmacol Ther, 28, p. 208-15
- (2024) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Inc.
- (2015) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Healthcare Corporation
- (2022) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hameln Pharma Ltd
- (2022) "Product Information. Xylocaine HCl (lidocaine)." Aspen Pharmacare Australia Pty Ltd
- Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of oral lignocaine https://pubmed.ncbi.nlm.nih.gov/10193676/
- Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine https://pubmed.ncbi.nlm.nih.gov/9832299/
betaxolol food
Applies to: betaxolol
MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.
MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.
References
- Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
- Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
- Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
- Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
- Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
- Cerner Multum, Inc. "Australian Product Information."
- Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
- Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
betaxolol food
Applies to: betaxolol
ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.
MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.
References
- Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35
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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