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Drug Interactions between artemether / lumefantrine and Bactimicina Allergy

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

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Interactions between your drugs

Moderate

loratadine lumefantrine

Applies to: Bactimicina Allergy (loratadine) and artemether / lumefantrine

MONITOR: Coadministration with lumefantrine may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. In vitro, lumefantrine significantly inhibits the activity of CYP450 2D6 at therapeutic plasma concentrations. Adverse effects of drugs that are primarily metabolized by CYP450 2D6 may be increased; however, clinical data have not been reported.

MANAGEMENT: Caution is advised if lumefantrine is used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lumefantrine is added to or withdrawn from therapy.

References

  1. "Product Information. Coartem (artemether-lumefantrine)." Novartis Pharmaceuticals (2009):

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Drug and food interactions

Moderate

lumefantrine food

Applies to: artemether / lumefantrine

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of artemether and lumefantrine. The mechanism is decreased clearance due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. High plasma levels of artemether and lumefantrine may increase the risk of QT interval prolongation and ventricular arrhythmias including torsade de pointes. In clinical trials, asymptomatic prolongation of the Fridericia-corrected QT interval (QTcF) by more than 30 msec from baseline was reported in approximately one-third of patients treated with artemether-lumefantrine, and prolongation by more than 60 msec was reported in more than 5% of patients. A few patients (0.4%) in the adult/adolescent population and no patient in the infant/children population experienced a QTcF greater than 500 msec. However, the possibility that these increases were disease-related cannot be ruled out. In a study of healthy adult volunteers, administration of the six-dose regimen of artemether-lumefantrine was associated with mean changes in QTcF from baseline of 7.45, 7.29, 6.12 and 6.84 msec at 68, 72, 96, and 108 hours after the first dose, respectively. There was a concentration-dependent increase in QTcF for lumefantrine. No subject had a greater than 30 msec increase from baseline nor an absolute increase to more than 500 msec.

ADJUST DOSING INTERVAL: Food enhances the oral absorption of artemether and lumefantrine. In healthy volunteers, the relative bioavailability of artemether increased by two- to threefold and that of lumefantrine by sixteenfold when administered after a high-fat meal as opposed to under fasted conditions.

MANAGEMENT: Patients receiving artemether-lumefantrine therapy should avoid the consumption of grapefruits and grapefruit juice. To ensure maximal oral absorption, artemether-lumefantrine should be taken with food. Inadequate food intake can increase the risk for recrudescence of malaria. Patients who are averse to food during treatment should be closely monitored and encouraged to resume normal eating as soon as food can be tolerated.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Coartem (artemether-lumefantrine)." Novartis Pharmaceuticals (2009):

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Minor

loratadine food

Applies to: Bactimicina Allergy (loratadine)

Theoretically, grapefruit juice may increase the plasma concentrations of loratadine as it does other drugs that are substrates of the CYP450 3A4 enzymatic pathway. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance of this potential interaction is unknown. Reported interactions with potent CYP450 3A4 inhibitors like clarithromycin, erythromycin and ketoconazole have produced substantial increases in the area under the plasma concentration-time curve (AUC) of loratadine and its active metabolite, descarboethoxyloratadine, without associated changes in the overall safety profile of the drug.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol 42 (1992): 313-7
  2. Bailey DG, Arnold JM, Munoz C, Spence JD "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther 53 (1993): 637-42
  3. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  4. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie 49 (1994): 522-4
  5. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther 54 (1993): 589-94
  6. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84
  7. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  8. Brannan MD, Reidenberg P, Radwanski E, et al. "Loratadine administered concomitantly with erythromycin: pharmacokinetic and electrocardiographic evaluations." Clin Pharmacol Ther 58 (1995): 269-78
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  11. Majeed A, Kareem A "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol 10 (1996): 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol 42 (1996): p662
  13. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
  14. Yumibe N, Huie K, Chen KJ, Snow M, Clement RP, Cayen MN "Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating antihistamine loratadine. Formation o descarboethoxyloratadine by CYP3A4 and CYP2D6." Biochem Pharmacol 51 (1996): 165-72
  15. Carr RA, Edmonds A, Shi H, Locke CS, Gustavson LE, Craft JC, Harris SI, Palmer R "Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of clarithromycin and loratadine after individual or concomitant administration." Antimicrob Agents Chemother 42 (1998): 1176-80
  16. Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402
  17. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  18. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther 64 (1998): 248-56
  19. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8
  20. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83
  21. Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32
  22. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  23. Eagling VA, Profit L, Back DJ "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol 48 (1999): 543-52
  24. Damkier P, Hansen LL, Brosen K "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol 48 (1999): 829-38
  25. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther 21 (1999): 1890-9
  26. Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol 49 (2000): 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol 49 (2000): 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  30. Kosoglou T, Salfi M, Lim JM, Batra VK, Cayen MN, Affrime MB "Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine." Br J Clin Pharmacol 50 (2000): 581-9
View all 30 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

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