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Drug Interactions between Efasin Expectorant SF and Levoprome

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

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Interactions between your drugs

Moderate

codeine methotrimeprazine

Applies to: Efasin Expectorant SF (codeine / guaifenesin / phenylpropanolamine) and Levoprome (methotrimeprazine)

MONITOR: Drugs that are inhibitors of CYP450 2D6 may interfere with the analgesic effect of codeine. The mechanism is decreased in vivo conversion of codeine to morphine, a metabolic reaction mediated by CYP450 2D6. If an inhibitor is started after a stable dose of codeine is achieved, reduced analgesia and possible opioid withdrawal may result. Conversely, ceasing CYP450 2D6 inhibitor therapy may lead to increased morphine levels, increasing the risk of opioid-related adverse effects.

MANAGEMENT: The possibility of reduced or inadequate pain relief should be considered in patients receiving codeine with drugs that inhibit CYP450 2D6. An increase in the codeine dosage or a different analgesic agent may be necessary in patients requiring therapy with CYP450 2D6 inhibitors. If concurrent therapy is used and the CYP450 2D6 inhibitor is stopped, the dose of codeine may need to be reduced and the patient should be monitored for signs and symptoms of respiratory depression or sedation. In addition, it should be noted that rolapitant, a moderate CYP450 2D6 inhibitor, may interfere with the analgesic effects of codeine for at least 28 days after administration of rolapitant. The manufacturer's prescribing information should be consulted for further information.

References

  1. Desmeules J, Dayer P, Gascon MP, Magistris M "Impact of genetic and environmental factors on codeine analgesia." Clin Pharmacol Ther 45 (1989): 122
  2. Sindrup SH, Arendt-Nielsen L, Brosen K, et al. "The effect of quinidine on the analgesic effect of codeine." Eur J Clin Pharmacol 42 (1992): 587-92
  3. Sindrup SH, Hofmann U, Asmussen J, Mikus G, Brosen K, Nielsen F, Ingwersen SH, Broen Christensen C "Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake." Eur J Clin Pharmacol 49 (1996): 503-9
  4. Sindrup SH, Brosen K, Bjerring P, et al. "Codeine increases pain threshold to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine." Clin Pharmacol Ther 49 (1991): 686-93
  5. Poulsen L, Brosen K, Srendt-Nielsen L, Gram LF, Elbaek K, Sindrup SH "Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects." Eur J Clin Pharmacol 51 (1996): 289-95
  6. Desmeules J, Gascon MP, Dayer P, Magistris M "Impact of environmental and genetic factors on codeine analgesia." Eur J Clin Pharmacol 41 (1991): 23-6
  7. Caraco Y, Sheller J, Wood JJ "Pharmacogenetic determination of the effects of codeine and prediction of drug interactions." J Pharmacol Exp Ther 278 (1996): 1165-74
  8. Caraco Y, Sheller J, Wood AJJ "Impact of ethnic origin and quinidine coadministration on codeine's disposition and pharmacodynamic effects." J Pharmacol Exp Ther 290 (1999): 413-22
  9. Hersh EV, Moore PA "Drug interactions in dentistry: the importance of knowing your CYPs." J Am Dent Assoc 135 (2004): 298-311
  10. Vevelstad M, Pettersen S, Tallaksen C, Brors O "O-demethylation of codeine to morphine inhibited by low-dose levomepromazine." Eur J Clin Pharmacol 65 (2009): 795-801
  11. Thorn CF, Klein TE, Altman RB "Codeine and morphine pathway." Pharmacogenet Genomics 19 (2009): 556-8
  12. Zhou SF "Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II." Clin Pharmacokinet 48 (2009): 761-804
  13. "Product Information. Varubi (rolapitant)." Tesaro Inc. (2015):
  14. "Product Information. Codeine Sulfate (codeine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2023):
View all 14 references

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Moderate

phenylpropanolamine methotrimeprazine

Applies to: Efasin Expectorant SF (codeine / guaifenesin / phenylpropanolamine) and Levoprome (methotrimeprazine)

GENERALLY AVOID: Phenothiazines may antagonize the pharmacologic effects of amphetamine, amphetamine derivatives, and other centrally-acting sympathomimetic agents (i.e., CNS stimulants). Conversely, these agents may diminish the neuroleptic efficacy of phenothiazines. The exact mechanism of interaction is unknown but may involve opposing effects on dopaminergic activity. Several clinical studies have demonstrated the reduction or lack of effect of amphetamines on weight loss in obese psychiatric patients treated with chlorpromazine and other neuroleptic agents. In one of these studies, dextroamphetamine also had no effect on sleep patterns. As for the reverse interaction, it is uncertain whether CNS stimulants actually antagonize the neuroleptic effect of phenothiazines, since CNS stimulants alone have been reported to cause or aggravate preexisting psychotic symptoms. Finally, it is conceivable that, because of their sympathomimetic effects, CNS stimulants may also potentiate the arrhythmogenicity of phenothiazines. A case of fatal ventricular arrhythmia was reported in a patient treated chronically with thioridazine who ingested a single capsule containing phenylpropanolamine 50 mg and chlorpheniramine 4 mg. However, a causal relationship was not established.

MANAGEMENT: Amphetamine, amphetamine derivatives, and other CNS stimulants should generally not be used, particularly for weight reduction, in patients treated with phenothiazines.

References

  1. Reid AA "Pharmacological antagonism between chlorpromazine and phenmetrazine in mental hospital patients." Med J Aust 1 (1964): 187-8
  2. Sletten IW, Ognjanov V, Menendez S, Sundland D, El-Toumi A "Weight reduction with chlorphentermine and phenmetrazine in obese psychiatric patients during chlorpromazine therapy." Curr Ther Res Clin Exp 9 (1967): 570-5
  3. Chouinard G, Ghadirian AM, Jones BD "Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac*C capsule." Can Med Assoc J 119 (1978): 729-31
  4. Casey JF, Hollister LE, Klett CJ, Lasky JJ, Caffey EM "Combined drug therapy of chronic schizophrenics." Am J Psychiatry 177 (1961): 997
  5. Modell W, Hussar AE "Failure of dextroamphetamine sulfate to incluence eating and sleeping patterns in obese schizophrenic patients." JAMA 193 (1965): 275-8
  6. Angrist B, Lee HK, Gershon S "The antagonism of amphetamine-induced symptomatology by a neuroleptic." Am J Psychiatry 131 (1974): 817-9
  7. Cornelius JR, Soloff PH, Reynolds CF, 3d "Paranoia, homicidal behavior, and seizures associated with phenylpropanolamine." Am J Psychiatry 141 (1984): 120-1
  8. Achor MB, Extein I "Diet aids, mania, and affective illness" Am J Psychiatry 138 (1981): 392
  9. Schaffer CB, Pauli MW "Psychotic reaction caused by proprietary oral diet agents." Am J Psychiatry 137 (1980): 1256-7
  10. Grieger TA, Clayton AH, Goyer PF "Affective disorder following use of phenylpropanolamine" Am J Psychiatry 147 (1990): 367-8
  11. Dietz AJ, Jr "Amphetamine-like reactions to phenylpropanolamine." JAMA 245 (1981): 601-2
  12. Norvenius G, Widerlov E, Lonnerholm G "Phenylpropanolamine and mental disturbances" Lancet 2 (1979): 1367-8
  13. Mueller SM "Neurologic complications of phenylpropanolamine use." Neurology 33 (1983): 650-2
  14. Lake CR, Tenglin R, Chernow B, Holloway HC "Psychomotor stimulant-induced mania in a genetically predisposed patient: a review of the literature and report of a case." J Clin Psychopharmacol 3 (1983): 97-100
  15. Lake CR "Manic psychosis after coffee and phenylpropanolamine." Biol Psychiatry 30 (1991): 401-4
  16. Lambert MT "Paranoid psychoses after abuse of proprietary cold remedies." Br J Psychiatry 151: (1987): 548-50
  17. Wharton BK "Nasal decongestants and paranoid psychosis." Br J Psychiatry 117 (1970): 439-40
  18. Dewsnap P, Libby G "A case of affective psychosis after routine use of proprietary cold remedy containing phenylpropanolamine" Hum Exp Toxicol 11 (1992): 295-6
  19. Finton CK, Barton M, Chernow B "Possible adverse effects of phenylpropanolamine (diet pills) on sympathetic nervous system function--caveat emptor!" Mil Med 147 (1982): 1072
  20. Stroe AE, Hall J, Amin F "Psychotic episode related to phenylpropanolamine and amantadine in a healthy female." Gen Hosp Psychiatry 17 (1995): 457-8
  21. Marshall RD, Douglas CJ "Phenylpropanolamine-induced psychosis: potential predisposing factors." Gen Hosp Psychiatry 16 (1994): 358-60
  22. "Product Information. Fastin (phentermine)." SmithKline Beecham PROD (2001):
  23. "Product Information. Cylert (pemoline)." Abbott Pharmaceutical PROD (2001):
  24. "Product Information. Ritalin (methylphenidate)." Novartis Pharmaceuticals PROD (2001):
  25. "Product Information. Desoxyn (methamphetamine)." Abbott Pharmaceutical PROD (2001):
  26. "Product Information. Dexedrine (dextroamphetamine)." SmithKline Beecham PROD (2001):
  27. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  28. "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn PROD (2001):
  29. "Product Information. Prelu-2 (phendimetrazine)." Boehringer-Ingelheim PROD (2001):
  30. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  31. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  32. Markowitz JS, Patrick KS "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet 40 (2001): 753-72
  33. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  34. "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc (2007):
View all 34 references

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Drug and food interactions

Moderate

phenylpropanolamine food

Applies to: Efasin Expectorant SF (codeine / guaifenesin / phenylpropanolamine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled 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. Mendelson J, Jones RT, Upton R, Jacob P 3rd "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68
  2. "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn PROD (2001):
  3. "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals (2012):

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Moderate

codeine food

Applies to: Efasin Expectorant SF (codeine / guaifenesin / phenylpropanolamine)

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther 15 (1974): 368-73
  2. Sturner WQ, Garriott JC "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA 223 (1973): 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol 41 (1991): 147-52
  4. Levine B, Saady J, Fierro M, Valentour J "A hydromorphone and ethanol fatality." J Forensic Sci 29 (1984): 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol 19 (1985): 398-401
  6. Carson DJ "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet 1 (1977): 894-7
  7. Rosser WW "The interaction of propoxyphene with other drugs." Can Med Assoc J 122 (1980): 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM "Distalgesic and ethanol-impaired function." Lancet 2 (1982): 384
  9. Kiplinger GF, Sokol G, Rodda BE "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther 212 (1974): 175-80
View all 9 references

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Moderate

methotrimeprazine food

Applies to: Levoprome (methotrimeprazine)

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

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

References

  1. Lutz EG "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA 236 (1976): 2422-3
  2. Freed E "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust 2 (1981): 44-5

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Moderate

phenylpropanolamine food

Applies to: Efasin Expectorant SF (codeine / guaifenesin / phenylpropanolamine)

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 "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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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

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

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