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Drug Interactions between caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate and Klonopin

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

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Interactions between your drugs

Moderate

phenylephrine caffeine

Applies to: caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate and caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate

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

  1. 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
  2. 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
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 references

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Moderate

sodium salicylate sodium citrate

Applies to: caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate and caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate

MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

References

  1. Berg KJ (1977) "Acute acetylsalicylic acid poisoning: treatment with forced alkaline diuresis and diuretics." Eur J Clin Pharmacol, 12, p. 111-6
  2. Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT (1982) "Diuresis or urinary alkalinisation for salicylate poisoning?" Br Med J (Clin Res Ed), 285, p. 1383-6
  3. Balali-Mood M, Prescott LF (1980) "Failure of alkaline diuresis to enhance diflunisal elimination." Br J Clin Pharmacol, 10, p. 163-5
  4. Berg KJ (1977) "Acute effects of acetylsalicylic acid in patients with chronic renal insufficiency." Eur J Clin Pharmacol, 11, p. 111-6
  5. Brouwers JRBJ, Desmet PAGM (1994) "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet, 27, p. 462-85
View all 5 references

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Minor

clonazePAM sodium citrate

Applies to: Klonopin (clonazepam) and caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate

A number of studies have reported that antacids can delay the gastrointestinal absorption and reduce the peak plasma concentration (Cmax) of some benzodiazepines, including clorazepate, chlordiazepoxide and diazepam, although the overall extent of absorption is generally not affected. The exact mechanism of interaction is unknown, but may involve delayed gastric emptying or cation binding of the benzodiazepine. As a result, benzodiazepine onset of action may be delayed and clinical effects diminished. However, one study reported a significant increase in diazepam absorption during coadministration with aluminum hydroxide, and there was a marginal increase in the onset of sedative effect. Aluminum hydroxide also increased triazolam Cmax and systemic exposure (AUC) in 11 dialysis patients such that their drug levels reached into the range observed for the matched controls. In contrast, another study by the same group of investigators found no significant effect of aluminum hydroxide on temazepam absorption or Cmax in 11 patients with end-stage renal disease. A multi-dose study also failed to find an effect of antacids on the steady-state levels of N-desmethyldiazepam, the active metabolite of clorazepate, although an acidic environment is thought to be necessary for the rapid conversion. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may consider separating the administration times of benzodiazepines and antacids or other oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 2 to 3 hours.

References

  1. Chun AH, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD (1977) "Effect of antacids on absorption of clorazepate." Clin Pharmacol Ther, 22, p. 329-35
  2. Nair SG, Gamble JA, Dundee JW, Howard PJ (1976) "The influence of three antacids on the absorption and clinical action of oral diazepam." Br J Anaesth, 48, p. 1175-80
  3. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J (1977) "Absorption rate, blood concentrations, and early response to oral chlordiazepoxide." Am J Psychiatry, 134, p. 559-62
  4. Greenblatt DJ, Allen MD, MacLaughlin DS, Harmatz JS, Shader RI (1978) "Diazepam absorption: effect of antacids and food." Clin Pharmacol Ther, 24, p. 600-9
  5. Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD (1978) "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide." Clin Pharmacol Ther, 24, p. 308-15
  6. Kroboth PD, Smith RB, Rault R, Silver MR, Sorkin MI, Puschett JB, Juhl RP (1985) "Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics." Clin Pharmacol Ther, 37, p. 453-9
  7. Kroboth PD, Smith RB, Silver MR, Rault R, Sorkin MI, Puschett JB, Juhl RP (1985) "Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics." Br J Clin Pharmacol, 19, p. 839-42
  8. Shader RI, Ciraulo DA, Greenblatt DJ, Harmatz JS (1982) "Steady-state plasma desmethyldiazepam during long-term clorazepate use: effects of antacids." Clin Pharmacol Ther, 31, p. 180-3
  9. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J (1976) "Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption." Clin Pharmacol Ther, 19, p. 234-9
View all 9 references

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Drug and food interactions

Moderate

pheniramine food

Applies to: caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate

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

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. 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.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Moderate

clonazePAM food

Applies to: Klonopin (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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Moderate

phenylephrine food

Applies to: caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate

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

  1. 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
  2. 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
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 references

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Minor

caffeine food

Applies to: caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52

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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.

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