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Drug Interactions between Rythmol SR and Tussi-Organidin NR

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

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Interactions between your drugs

Moderate

codeine propafenone

Applies to: Tussi-Organidin NR (codeine / guaifenesin) and Rythmol SR (propafenone)

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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Drug and food interactions

Moderate

propafenone food

Applies to: Rythmol SR (propafenone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of propafenone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. In over 90% of patients, propafenone is rapidly and extensively converted to 2 active metabolites: 5-hydroxypropafenone via CYP450 2D6 and N-depropylpropafenone (norpropafenone) via CYP450 3A4 and 1A2. In less than 10% of patients (approximately 6% of Caucasians in the U.S. population), however, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed, or minimally formed, due to a genetic deficiency in CYP450 2D6. In these poor metabolizers of CYP450 2D6, clearance of propafenone via the CYP450 3A4 and 1A2 metabolic pathways becomes more important, and inhibition of these pathways may substantially increase systemic exposure to propafenone. Likewise, patients taking concomitant inhibitors of CYP450 2D6 and 3A4 may experience similar pharmacokinetic effects. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to propafenone may result in proarrhythmic events and exaggerated beta-adrenergic blocking activity.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with propafenone.

References

  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK "Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites." Mol Pharmacol 43 (1993): 120-6
  2. "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline (2011):
  3. "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated (2023):
  4. "Product Information. Propafenone (propafenone)." Accord-UK Ltd (2022):
View all 4 references

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Moderate

codeine food

Applies to: Tussi-Organidin NR (codeine / guaifenesin)

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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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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