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Drug Interactions between Allfen CDX and Pacerone

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

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Interactions between your drugs

Moderate

amiodarone codeine

Applies to: Pacerone (amiodarone) and Allfen CDX (codeine / guaifenesin)

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

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Drug and food interactions

Major

amiodarone food

Applies to: Pacerone (amiodarone)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered amiodarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 11 nonsmoking, healthy volunteers, grapefruit juice (300 mL with drug administration, then 3 hours and 9 hours later) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amiodarone (17 mg/kg single dose) by 84% and 50%, respectively, compared to water. Formation of the pharmacologically active metabolite, N-desethylamiodarone (N-DEA), was completely inhibited. Clinically, this interaction can lead to altered efficacy of amiodarone, since antiarrhythmic properties of amiodarone and N-DEA appear to differ. In the study, mean increases in PR and QTc intervals of 17.9% and 11.3%, respectively, were observed 6 hours postdose with water, while increases of 10.2% and 3.3%, respectively, were observed after administration with grapefruit juice.

ADJUST DOSING INTERVAL: Food increases the rate and extent of absorption of amiodarone. The mechanism appears to involve the effect of food-induced physiologic changes on drug release from its formulation. In 30 healthy volunteers, administration of a single 600 mg dose of amiodarone following a high-fat meal resulted in a Cmax and AUC that were 3.8 and 2.4 times the respective values under fasting conditions. The time to reach peak plasma concentration (Tmax) was decreased by 37%, indicating an increased rate of absorption. Mean Cmax and AUC for the active metabolite, N-DEA, also increased by 32% and 55%, respectively, but there was no change in the Tmax.

MANAGEMENT: Patients treated with oral amiodarone should avoid consumption of grapefruits and grapefruit juice. In addition, oral amiodarone should be administered consistently with regard to meals.

References

  1. (2002) "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories
  2. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  3. Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR (2001) "Bioavailability of Amiodarone tablets administered with and without food in healthy subjects." Am J Cardiol, 87, p. 432-5

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Moderate

codeine food

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

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