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Drug Interactions between Mebaral and penbutolol

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

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Interactions between your drugs

Moderate

penbutolol mephobarbital

Applies to: penbutolol and Mebaral (mephobarbital)

MONITOR: Coadministration with barbiturates may decrease the plasma concentrations and pharmacologic effects of certain beta-blockers when administered orally. The proposed mechanism is barbiturate induction of hepatic microsomal and first-pass metabolism. The interaction has been studied with alprenolol, metoprolol and timolol, but probably can occur with any beta-blocker that is primarily metabolized in the liver such as propranolol. In six healthy volunteers, pretreatment with pentobarbital (100 mg daily for 10 days) reduced the plasma levels of alprenolol (200 mg single oral dose) and its metabolite 4-hydroxyalprenolol by approximately 40% without altering their plasma half-lives. The inhibition of exercise-induced tachycardia during a 7-hour period following alprenolol administration was reduced from 14% to 10.7% by pentobarbital, and the reduction was proportional to the decreased drug levels. In another study, pentobarbital reduced alprenolol levels by 59% and 4-hydroxyalprenolol levels by 24% in 6 hypertensive patients treated with alprenolol 400 mg twice daily. The effect of pentobarbital was significant after 3 doses and declined over 4 to 5 days after discontinuation. The decreases were associated with a 6% increase in pulse rate and 8% increase in systolic and 9% increase in diastolic blood pressure, as well as an 18% reduction in inhibition of exercise tachycardia by alprenolol. In eight healthy subjects, administration of metoprolol (100 mg single oral dose) with pentobarbital (100 mg daily for 10 days) resulted in a mean 32% reduction in metoprolol systemic exposure (AUC) compared to administration alone. The same dose of pentobarbital given for 7 days reduced AUC of timolol (10 mg) by just 24% in 12 healthy volunteers.

MANAGEMENT: Barbiturates may variously reduce the effects of certain beta-blockers when given for more than a few days. Pharmacologic response to beta-blockers should be monitored more closely whenever a barbiturate is added to or withdrawn from therapy, and the beta-blocker dosage adjusted as necessary. Renally excreted beta-blockers such as atenolol, carteolol, nadolol, or sotalol are not expected to interact.

References

  1. Branch RA, Herman RJ (1984) "Enzyme induction and beta-adrenergic receptor blocking drugs." Br J Clin Pharmacol, 17, s77-84
  2. Mantyla R, Mannisto P, Nykanen S, Koponen A, Lamminsivu U (1983) "Pharmacokinetic interactions of timolol with vasodilating drugs, food and phenobarbitone in healthy human volunteers." Eur J Clin Pharmacol, 24, p. 227-30
  3. Seideman P, Borg K, Haglund K, Von Bahr C, (1987) "Decreased plasma concentrations and clinical effects of alprenolol during combined treatment with pentobarbitone in hypertension." Br J Clin Pharmacol, 23, p. 267-71
  4. Collste P, Seideman P, Borg K, Haglund K, Von Bahr C (1979) "Influence of pentobarbital on effect and plasma levels of alprenolol and 4-hydroxy-alprenolol." Clin Pharmacol Ther, 25, p. 423-7
  5. Haglund K, Seideman P, Colliste P, Borg KO, von Bahr C (1979) "Influence of pentobarbital on metoprolol plasma levels." Clin Pharmacol Ther, 26, p. 326-9
  6. Sotaniemi EA, Anttila M, Pelkonen RO, Jarvensivu P, Sundquist H (1979) "Plasma clearance of propranolol and sotalol and hepatic drug-metabolizing enzyme activity." Clin Pharmacol Ther, 26, p. 153-61
View all 6 references

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Drug and food interactions

Major

mephobarbital food

Applies to: Mebaral (mephobarbital)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
View all 5 references

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Moderate

penbutolol food

Applies to: penbutolol

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

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. 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
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

penbutolol food

Applies to: penbutolol

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

  1. 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

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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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