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Drug Interactions between digoxin and Klonopin Wafer

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

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Interactions between your drugs

Moderate

clonazePAM digoxin

Applies to: Klonopin Wafer (clonazepam) and digoxin

MONITOR: Benzodiazepines may increase serum levels of digoxin. The mechanism is unknown, but may be related to alterations of digoxin protein binding. Data have been conflicting; however, some cases of digoxin toxicity have been reported. Elderly patients may have a greater risk of developing toxicity.

MANAGEMENT: Close observation for clinical and laboratory evidence of digoxin toxicity is recommended if these drugs must be used together. Patients should be advised to notify their physician if they experience nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

References

  1. Ochs HR, Greenblatt DJ, Verburg-Ochs B (1985) "Effect of alprazolam on digoxin kinetics and creatinine clearance." Clin Pharmacol Ther, 38, p. 595-8
  2. Rodin SM, Johnson BF (1988) "Pharmacokinetic interactions with digoxin." Clin Pharmacokinet, 15, p. 227-44
  3. Tollefson G, Lesar T, Grothe D, Garvey M (1984) "Alprazolam-related digoxin toxicity." Am J Psychiatry, 141, p. 1612-3
  4. Castillo-Ferrando JR, Garcia M, Carmona J (1980) "Digoxin levels and diazepam." Lancet, 2, p. 368
  5. Castillo-Ferrando JR, Prieto AC, Brasas F (1983) "Effects of benzodiazepines on digoxin tissue concentrations and plasma protein binding." J Pharm Pharmacol, 35, p. 462-3
  6. Tollefson G, Lesar T, Grothe D, Garvey M (1984) "Alprazolam-related digoxin toxicity." Am J Psychiatry, 141, p. 1612-4
  7. Guven H, Tuncok Y, Guneri S, Cavdar C, Fowler J (1993) "Age-related digoxin-alprazolam interaction." Clin Pharmacol Ther, 54, p. 42-4
View all 7 references

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Drug and food interactions

Moderate

clonazePAM food

Applies to: Klonopin Wafer (clonazepam)

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  2. Whiting B, Lawrence JR, Skellern GG, Meier J (1979) "Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide." Br J Clin Pharmacol, 7, p. 95-100
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB (1984) "Alprazolam pharmacokinetics in alcoholic liver disease." J Clin Pharmacol, 24, p. 113-9
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI (1984) "Pharmacokinetic noninteraction of triazolam and ethanol." J Clin Psychopharmacol, 4, p. 106-7
  6. Staak M, Raff G, Nusser W (1979) "Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol." Int J Clin Pharmacol Biopharm, 17, p. 205-12
  7. Nichols JM, Martin F, Kirkby KC (1993) "A comparison of the effect of lorazepam on memory in heavy and low social drinkers." Psychopharmacology (Berl), 112, p. 475-82
View all 7 references

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Minor

digoxin food

Applies to: digoxin

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References

  1. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. (2001) "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther, 70, p. 311-6

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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.

See also

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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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