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Drug Interactions between Levsin with Phenobarbital and Metro

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

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Interactions between your drugs

Moderate

metroNIDAZOLE PHENobarbital

Applies to: Metro (metronidazole) and Levsin with Phenobarbital (hyoscyamine / phenobarbital)

ADJUST DOSE: Coadministration with a barbiturate may significantly decrease the plasma concentrations and pharmacologic effects of nitroimidazoles. The proposed mechanism is barbiturate induction of nitroimidazole metabolism via hepatic microsomal enzymes. The interaction has been reported with metronidazole and has been attributed to treatment failure in patients with trichomoniasis, giardiasis, or amebiasis given the normally recommended dosages of metronidazole while being treated concomitantly with phenobarbital. Significantly increased clearance and shortened half-life of metronidazole were demonstrated. In many cases, metronidazole dosage had to be doubled or even tripled to achieve a cure. No data are available for tinidazole.

MANAGEMENT: Patients treated concomitantly with a barbiturate may require a higher dosage of metronidazole to achieve a cure. Two- to threefold dosage increases are not uncommon. Pharmacologic response to metronidazole should be monitored and the dosage adjusted as necessary. Given its structural similarities to metronidazole, the same precaution may be applicable during therapy with tinidazole, although clinical data are lacking.

References

  1. "Product Information. Flagyl (metronidazole)." Searle PROD (2001):
  2. Loft S, Sonne J, Poulsen HE, Peterson KT, Jorgensen BG, Dossing M "Inhibition and induction of metronidazole and antipyrine metabolism." Eur J Clin Pharmacol 32 (1987): 35-41
  3. Mead PB, Gibson M, Schentag JJ, Ziemniak JA "Possible alteration of metronidazole metabolism by phenobarbital." N Engl J Med 306 (1982): 1490
  4. Gupte S "Phenobarbital and metabolism of metronidazole." N Engl J Med 308 (1983): 529
  5. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):
View all 5 references

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Drug and food interactions

Major

metroNIDAZOLE food

Applies to: Metro (metronidazole)

CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

References

  1. Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15
  2. Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3
  3. Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80
  4. "Product Information. Flagyl (metronidazole)." Searle PROD (2001):
  5. Edwards DL, Fink PC, Van Dyke PO "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm 5 (1986): 999-1000
  6. Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4
  8. Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8
  9. "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc (2017):
View all 9 references

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Major

PHENobarbital food

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital)

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

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Moderate

hyoscyamine food

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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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

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