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Drug Interactions between Anoro Ellipta and quinine

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

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Moderate

quiNINE vilanterol

Applies to: quinine and Anoro Ellipta (umeclidinium / vilanterol)

MONITOR: Beta-2 adrenergic agonists can cause dose-related prolongation of the QT interval and potassium loss. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Clinically significant prolongation of QT interval and hypokalemia occur infrequently when beta-2 agonists are inhaled at normally recommended dosages. However, these effects may be more common when the drugs are administered systemically or when recommended dosages are exceeded.

MANAGEMENT: Caution is recommended if beta-2 agonists are used in combination with other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Whyte KF, Addis GJ, Whitesmith R, Reid JL (1987) "The mechanism of salbutamol-induced hypokalaemia." Br J Clin Pharmacol, 23, p. 65-71
  2. Larsson S, Svedmyr N (1977) "Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol inasthmatics." Am Rev Respir Dis, 116, p. 861-9
  3. Hastwell G, Lambert BE (1978) "The effect of oral salbutamol on serum potassium and blood sugar." Br J Obstet Gynaecol, 85, p. 767-9
  4. (1981) "Hypokalaemia due to salbutamol overdosage." Br Med J (Clin Res Ed), 283, p. 500-1
  5. Kantola I, Tarssanen L (1986) "Hypokalemia from usual salbutamol dosage ." Chest, 89, p. 619-20
  6. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE (1990) "Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma." Lancet, 336, p. 1396-9
  7. Gross TL, Sokol RJ (1980) "Severe hypokalemia and acidosis: a potential complication of beta- adrenergic treatment." Am J Obstet Gynecol, 138, p. 1225-6
  8. Clifton GD, Hunt BA, Patel RC, Burki NK (1990) "Effects of sequential doses of parenteral terbutaline on plasma levels of potassium and related cardiopulmonary responses." Am Rev Respir Dis, 141, p. 575-9
  9. Hurlbert BJ, Edelman JD, David K (1981) "Serum potassium levels during and after terbutaline." Anesth Analg, 60, p. 723-5
  10. Bengtsson B, Fagerstrom PO (1982) "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther, 31, p. 726-32
  11. Gelmont DM, Balmes JR, Yee A (1988) "Hypokalemia induced by inhaled bronchodilators." Chest, 94, p. 763-6
  12. Sanders JP, Potter DE, Ellis S, Bee DE, Grant JA (1977) "Metabolic and cardiovascular effects of carbuterol and metaproterenol." J Allergy Clin Immunol, 60, p. 174-9
  13. (2002) "Product Information. Proventil (albuterol)." Schering Corporation
  14. Windom H, Grainger J, Burgess C, Crane J, Pearce N, Beasley R (1990) "A comparison of the haemodynamic and hypokalaemic effects of inhaled pirbuterol and salbutamol." N Z Med J, 103, p. 259-61
  15. "Product Information. Serevent (salmeterol)." Glaxo Wellcome
  16. (2001) "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals
  17. Dickens GR, Mccoy RA, West R, Stapczynski JS, Clifton GD (1994) "Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease." Pharmacotherapy, 14, p. 729-33
  18. Tveskov C, Djurhuus MS, Klitgaard NAH, Egstrup K (1994) "Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta(2)-adrenergic stimulation with terbutaline in healthy subjects." Chest, 106, p. 1654-9
  19. Braden GL, vonOeyen PT, Germain MJ, Watson DJ, Haag BL (1997) "Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences." Kidney Int, 51, p. 1867-75
  20. Rakhmanina NY, Kearns GL, Farrar HC (1998) "Hypokalemia in an asthmatic child from abuse of albuterol metered dose inhaler." Pediatr Emerg Care, 14, p. 145-7
  21. (2001) "Product Information. Xopenex (levalbuterol)." Sepracor Inc
  22. (2001) "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals
  23. Ferguson GT, Funck-Brentano C, Fischer T, Darken P, Reisner C (2003) "Cardiovascular Safety of Salmeterol in COPD." Chest, 123, p. 1817-24
  24. Milic M, Bao X, Rizos D, Liu F, Ziegler MG (2006) "Literature review and pilot studies of the effect of qt correction formulas on reported beta(2)-agonist-induced QTc prolongation." Clin Ther, 28, p. 582-90
  25. (2006) "Product Information. Brovana (arformoterol)." Sepracor Inc
  26. Lowe MD, Rowland E, Brown MJ, Grace AA (2001) "Beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium." Heart, 86, p. 45-51
  27. Sun ZH, Swan H, Vitasalo M, Toivonen L (1998) "Effects of epinephrine and phenylephrine on QT interval dispersion in congenital long QT syndrome." J Am Coll Cardiol, 31, p. 1400-5
  28. (2011) "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals
  29. (2013) "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline
  30. (2014) "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim
View all 30 references

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Drug and food interactions

Minor

quiNINE food

Applies to: quinine

Coadministration with grapefruit juice does not appear to affect the pharmacokinetics of quinine in a clinically relevant manner. Although grapefruit juice is an inhibitor of CYP450 3A4 and quinine is metabolized by this pathway to its major metabolite, 3-hydroxyquinine, a study of ten healthy volunteers found no significant differences in quinine peak plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life, systemic exposure (AUC), or apparent oral clearance (Cl/F) when a single 600 mg oral dose of quinine sulfate was administered in combination with 200 mL of orange juice (control), half-strength grapefruit juice, and full-strength grapefruit juice twice daily for 6 days each, separated by a 2-week washout period. Relative to the control period, the apparent renal clearance of quinine was markedly increased by 81% during treatment with half-strength grapefruit juice. However, since renal clearance accounts for approximately 6% of the total clearance of quinine, this change would likely have minimal clinical impact. The lack of a significant interaction is probably due to the fact that grapefruit juice primarily inhibits intestinal rather than hepatic CYP450 3A4, and quinine is not known to undergo significant presystemic metabolism as evidenced by its relatively high oral bioavailability (76% to 88%). Nevertheless, excessive consumption of grapefruit juice and tonic water (which contains quinine) was suspected as the cause of torsade de pointes arrhythmia in a patient with a history of asymptomatic long QT syndrome. Treatment with magnesium sulfate and metoprolol had no effect, but the arrhythmia resolved spontaneously 48 hours after discontinuation of the drinks. Based on current data, moderate grapefruit juice consumption is probably safe for the majority of patients taking quinine.

References

  1. Ho PC, Chalcroft SC, Coville PF, Wanwimolruk S (1999) "Grapefruit juice has no effect on quinine pharmacokinetics." Eur J Clin Pharmacol, 55, p. 393-8
  2. Hermans K, Stockman D, Van den Branden F (2003) "Grapefruit and tonic: a deadly combination in a patient with the long QT syndrome." Am J Med, 114, p. 511-2
  3. (2006) "Product Information. Qualaquin (quinine)." AR Scientific Inc
  4. Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S (1997) "Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine." Br J Clin Pharmacol, 43, p. 245-52
  5. Mirghani RA, Yasar U, Zheng T, et al. (2002) "Enzyme kinetics for the formation of 3-hydroxyquinine and three new metabolites of quinine in vitro; 3-hydroxylation by CYP3A4 is indeed the major metabolic pathway." Drug Metab Dispos, 30, p. 1368-71
View all 5 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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