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Drug Interactions between Evotaz and Romilar AC

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

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Interactions between your drugs

Moderate

codeine cobicistat

Applies to: Romilar AC (codeine / guaifenesin) and Evotaz (atazanavir / cobicistat)

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

atazanavir food

Applies to: Evotaz (atazanavir / cobicistat)

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):

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Moderate

codeine food

Applies to: Romilar AC (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.

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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