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Drug Interactions between emtricitabine / nelfinavir / tenofovir and methysergide maleate

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

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Interactions between your drugs

Major

methysergide maleate nelfinavir

Applies to: methysergide maleate and emtricitabine / nelfinavir / tenofovir

CONTRAINDICATED: Coadministration with protease inhibitors (PIs), particularly ritonavir, may significantly increase the plasma concentrations of ergot derivatives. The mechanism is PI inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of ergotamine and related drugs. Clinical ergotism, occasionally resulting in surgical amputation or death, has been reported in patients receiving ergotamine tartrate with ritonavir, indinavir, and/or nelfinavir. Even small, single doses of ergotamine have been involved in clinically significant interactions.

MANAGEMENT: Given the potential for ergot toxicity characterized by peripheral vasospasm, ischemia, thrombosis, tachycardia and hypertension, concomitant use of ergot derivatives with protease inhibitors is considered contraindicated.

References

  1. (2002) "Product Information. D.H.E. 45 (dihydroergotamine)." Sandoz Pharmaceuticals Corporation
  2. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  3. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  4. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  5. (2001) "Product Information. Migranal (dihydroergotamine nasal)." Novartis Pharmaceuticals
  6. Rosenthal E, Sala F, Chichmanian RM, Batt M, Cassuto JP (1999) "Ergotism related to concurrent administration of ergotamine tartrate and indinavir." JAMA, 281, p. 987
  7. Liaudet L, Buclin T, Jaccard C, Eckert P (1999) "Severe ergotism associated with interaction between ritonavir and ergotamine." Br Med J, 318, p. 771
  8. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  9. Caballero-Granado FJ, Viciana P, Cordero E, Gomez-Vera MJ, del Nozal M, Lopez-Cortes LF (1997) "Ergotism related to concurrent administration of ergotamine tartrate and ritonavir in an AIDS patient." Antimicrob Agents Chemother, 41, p. 1207
  10. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  11. Eadie MJ (2001) "Clinically significant drug interactions with agents specific for migraine attacks." Cns Drugs, 15, p. 105-18
  12. Spiegel M, Schmidauer C, Kampfl A, Sarcletti M, Poewe W (2001) "Cerebral ergotism under treatment with ergotamine and ritonavir." Neurology, 57, p. 743-4
  13. Mangum EM, Graham KK (2001) "Lopinavir-Ritonavir: a new protease inhibitor." Pharmacotherapy, 21, p. 1352-63
  14. Vila A, Mykietiuk A, Bonvehi P, Temporiti E, Uruena A, Herrera F (2001) "Clinical ergotism induced by ritonavir." Scand J Infect Dis, 33, p. 788-9
  15. Montero A, Giovannoni AG, Tvrde PL (1999) "Leg ischemia in a patient receiving ritonavir and ergotamine." Ann Intern Med, 130, p. 329
  16. Liaudet L (1999) "Severe ergotism associated with interaction between ritonavir and ergotamine." BMJ, 318, p. 771
  17. Mortier E, Pouchet J, Vinceneux P, Lalande M (2001) "Ergotism related to interaction between nelfinavir and ergotamine." Am J Med, 110, p. 594
  18. Blanche P, Rigolet A, Gombert B, Ginsburg C, Salmon D, Sicard D (1999) "Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir." Postgrad Med J, 75, p. 546-7
  19. Baldwin ZK, Ceraldi CC (2003) "Ergotism associated with HIV antiviral protease inhibitor therapy." J Vasc Surg, 37, p. 676-8
  20. Tribble MA, Gregg CR, Margolis DM, Amirkhan R, Smith JW (2002) "Fatal ergotism induced by an HIV protease inhibitor." Headache, 42, p. 694-5
  21. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  22. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  23. (2004) "Product Information. Cafergot (caffeine-ergotamine)." Novartis Pharmaceuticals
  24. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  25. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  26. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  27. (2011) "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation
  28. (2011) "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals
  29. Srisuma S, Lavonas EJ, Wananukul W (2014) "Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors." Clin Toxicol (Phila), p. 1-4
View all 29 references

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Drug and food interactions

Moderate

methysergide maleate food

Applies to: methysergide maleate

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "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, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. 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
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
View all 32 references

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Minor

tenofovir food

Applies to: emtricitabine / nelfinavir / tenofovir

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.

References

  1. (2001) "Product Information. Viread (tenofovir)." Gilead Sciences

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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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