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Drug Interactions between emtricitabine / lopinavir / ritonavir / tenofovir disoproxil and fluticasone / umeclidinium / vilanterol

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

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Interactions between your drugs

Major

fluticasone ritonavir

Applies to: fluticasone / umeclidinium / vilanterol and emtricitabine / lopinavir / ritonavir / tenofovir disoproxil

GENERALLY AVOID: Coadministration with ritonavir may significantly increase the systemic exposure to fluticasone following intranasal administration or oral inhalation. The mechanism is ritonavir inhibition of fluticasone metabolism via hepatic and intestinal CYP450 3A4. In 18 healthy subjects, administration of fluticasone propionate nasal spray (200 mcg once daily) in combination with ritonavir (100 mg twice daily) for 7 days resulted in an approximately 25-fold increase in fluticasone peak plasma concentration (Cmax) and 350-fold increase in systemic exposure (AUC) compared to administration alone. These changes were accompanied by an 86% decrease in mean plasma cortisol AUC. Systemic glucocorticoid adverse effects such as adrenal suppression, Cushing's syndrome, osteoporosis, and exacerbation of diabetes mellitus have been reported during postmarketing use of orally inhaled or intranasal fluticasone in patients receiving ritonavir-containing antiretroviral regimens. In an analysis of 25 suspected cases of the interaction reported in the medical literature, the mean dosage of orally inhaled fluticasone was 992 mcg/day (range 500 to 2000 mcg/day) in adult cases and 455 mcg/day (range 200 to 1000 mcg/day) in pediatric cases. Dosages of ritonavir used included both low, "boosting" dosages (100 to 200 mg daily) and high, "treatment" dosages (800 to 1200 mg/day). The average onset of cushingoid appearance was approximately 2.75 months (range 2 weeks to 6 months) in adult cases and 2.1 months (range 2 weeks to 3 months) in pediatric cases. For the three cases involving intranasal fluticasone, the dosage used ranged from 200 to 800 mcg/day and the onset of cushingoid appearance ranged from 5 to 18 months of concomitant use with ritonavir. Recovery of adrenal function was reportedly slow in some patients following discontinuation of fluticasone. Investigators suggest that this could be related to the highly lipophilic nature of fluticasone, which allows for prolonged seepage of drug into the circulation from fat stores.

MANAGEMENT: The use of intranasal or orally inhaled fluticasone in combination with ritonavir is not recommended unless the potential benefit outweighs the risk of systemic side effects. Alternatives to fluticasone should be considered whenever possible if ritonavir must be used. A less potent, less lipophilic, and/or shorter-acting agent such as beclomethasone, budesonide, flunisolide or triamcinolone may be appropriate, although probably most, if not all, corticosteroids can interact with ritonavir to some extent. The lowest effective dosage of orally inhaled corticosteroid should be used, and further adjustments made as necessary according to therapeutic response and tolerance. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. It is important to distinguish between hypercorticism and the lipodystrophy syndrome caused by antiretroviral treatment, as the overlap of certain clinical features may delay the recognition and diagnosis of Cushing's syndrome. In general, the lack of peripheral atrophy and the presence of abdominal striae, easy bruising, and facial plethora would suggest iatrogenic Cushing's syndrome rather than antiretroviral-related lipodystrophy. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with ritonavir, a progressive dosage reduction may be required over a longer period if fluticasone is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma). Systemic glucocorticoids may be necessary until adrenal function recovers.

References (33)
  1. (2001) "Product Information. Flonase (fluticasone)." Glaxo Wellcome
  2. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  3. Lonnebo A, Grahnen A, Jansson B, Brundin RM, Lingandersson A, Eckernas SA (1996) "An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers." Eur J Clin Pharmacol, 49, p. 459-63
  4. Grahnen A, Eckernas SA, Brundin RM, Ling-Andersson A (1994) "An assessment of the systemic activity of single doses of inhaled fluticasone propionate in healthy volunteers." Br J Clin Pharmacol, 38, p. 521-5
  5. (2001) "Product Information. Flovent (fluticasone)." Glaxo Wellcome
  6. Sastre J (1997) "Pharmacology of fluticasone propionate." J Investig Allergol Clin Immunol, 7, p. 382-4
  7. Kelly HW (1998) "Comparison of inhaled corticosteroids." Ann Pharmacother, 32, p. 220-32
  8. Lipworth BJ (1999) "Systemic adverse effects of inhaled corticosteroid therapy - A systematic review and meta-analysis." Arch Intern Med, 159, p. 941-55
  9. Hillebrand-Haverkort ME, Prummel MF, ten Veen JH (1999) "Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone." AIDS, 13, p. 1803
  10. Gupta SK, Dube MP (2002) "Exogenous Cushing syndrome mimicking human immunodeficiency virus lipodystrophy." Clin Infect Dis, 35, E69-71
  11. Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA (2005) "Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in HIV-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases." J Clin Endocrinol Metab, 90, p. 4394-8
  12. Gillett MJ, Cameron PU, Nguyen HV, Hurley DM, Mallal SA (2005) "Iatrogenic Cushing's syndrome in an HIV-infected patient treated with ritonavir and inhaled fluticasone." AIDS, 19, p. 740-1
  13. Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J (2005) "Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction." Intern Med J, 35, p. 67-8
  14. Johnson SR, Marion AA, Vrchoticky T, Emmanuel PJ, Lujan-Zilbermann J (2006) "Cushing syndrome with secondary adrenal insufficiency from concomitant therapy with ritonavir and fluticasone." J Pediatr, 148, p. 386-388
  15. Li AM (2006) "Ritonavir and fluticasone: Beware of this potentially fatal combination." J Pediatr, 148, p. 294-5
  16. Arrington-Sanders R, Hutton N, Siberry GK (2006) "Ritonavir-fluticasone interaction causing Cushing syndrome in HIV-infected children and adolescents." Pediatr Infect Dis J, 25, p. 1044-1048
  17. Pessanha TM, Campos JM, Barros AC, Pone MV, Garrido JR, Pone SM (2007) "Iatrogenic Cushing's syndrome in a adolescent with AIDSs on ritonavir and inhaled fluticasone. case report and literature review." AIDS, 21, p. 529-32
  18. Bhumbra NA, Sahloff EG, Oehrtman SJ, Horner JM (2007) "Exogenous Cushing syndrome with inhaled fluticasone in a child receiving lopinavir/ritonavir." Ann Pharmacother, 41, p. 1306-9
  19. Jinno S, Goshima C (2008) "Progression of Kaposi sarcoma associated with iatrogenic Cushing syndrome in a person with HIV/AIDS." AIDS Read, 18, p. 100-4
  20. Molimard M, Girodet PO, Pollet C, et al. (2008) "Inhaled corticosteroids and adrenal insufficiency: prevalence and clinical presentation." Drug Saf, 31, p. 769-74
  21. Foisy MM, Yakiwchuk EM, Chiu I, Singh AE (2008) "Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature." HIV Med, 9, p. 389-96
  22. Valin N, De Castro N, Garrait V, Bergeron A, Bouche C, Molina JM (2009) "Iatrogenic Cushing's syndrome in HIV-infected patients receiving ritonavir and inhaled fluticasone: description of 4 new cases and review of the literature." J Int Assoc Physicians AIDS Care, 8, p. 113-21
  23. Daveluy A, Raignoux C, Miremont-Salame G, et al. (2009) "Drug interactions between inhaled corticosteroids and enzymatic inhibitors." Eur J Clin Pharmacol
  24. Nocent C, Raherison C, Dupon M, Taytard A (2004) "Unexpected effects of inhaled fluticasone in an HIV patient with asthma." J Asthma, 41, p. 793-5
  25. Kedem E, Shahar E, Hassoun G, Pollack S (2010) "Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient." J Asthma, 47, p. 830-1
  26. Pearce RE, Leeder JS, Kearns GL (2006) "Biotransformation of fluticasone: in vitro characterization." Drug Metab Dispos, 34, p. 1035-40
  27. Vassiliadi D, Tsagarakis S (2007) "Unusual causes of Cushing's syndrome." Arq Bras Endocrinol Metabol, 51, p. 1245-52
  28. Rouanet I, Peyriere H, Mauboussin JM, Vincent D (2003) "Cushing's syndrome in a patient treated by ritonavir/lopinavir and inhaled fluticasone." HIV Med, 4, p. 149-50
  29. Brus R (1999) "Effects of high-dose inhaled corticosteroids on plasma cortisol consentrations in healthy adults." Arch Intern Med, 159, p. 1903-8
  30. Todd GR, Acerini CL, Ross-Russell, Zahra S, Warner JT, McCance D (2002) "Survey of adrenal crisis associated witwh inhaled corticosteroids in the United Kingdom." Arch Dis Child, 87, p. 457-61
  31. Fardon TC, Lee DK, Haggart K, McFarlane LC, Lipworth BJ (2004) "Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate." Am J Respir Crit Care Med, 170, p. 960-6
  32. Boorsma M, Andersson N, Larsson P, Ullman A (1996) "Assessment of the relative systemic potency of inihaled fluticasone and budesonide." Eur Respir J, 9, p. 1427-32
  33. Bernecker C, West TB, Mansmann G, Scherbaum WA, Willenberg HS (2012) "Hypercortisolism caused by ritonavir associated inhibition of CYP 3A4 under inhalative glucocorticoid therapy. 2 case reports and a review of the literature." Exp Clin Endocrinol Diabetes, 120, p. 125-7

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Moderate

ritonavir tenofovir

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir disoproxil and emtricitabine / lopinavir / ritonavir / tenofovir disoproxil

MONITOR: Coadministration with ritonavir, with or without lopinavir, has been suggested in postmarketing reports to increase the proximal tubular intracellular concentrations of tenofovir and potentiate the risk of tenofovir-induced nephrotoxicity. The proposed mechanism is ritonavir inhibition of tenofovir renal tubular secretion into the urine via multidrug resistance protein MRP2. Analysis of data from a compassionate access study in which 271 patients with advanced HIV disease received the combination for a mean duration of 63 weeks revealed no clinically significant nephrotoxicity associated with coadministration. However, there have been case reports of renal failure associated with acute tubular necrosis, Fanconi's syndrome, and nephrogenic diabetes insipidus in patients treated with tenofovir disoproxil fumarate in combination with ritonavir. Some patients had incomplete recovery of renal function more than a year after cessation of tenofovir therapy. Ritonavir given in combination with lopinavir has also been reported to modestly increase the plasma concentrations of tenofovir. In contrast, both slight decreases and no change in lopinavir and ritonavir concentrations have been reported.

MANAGEMENT: Caution is advised if tenofovir disoproxil fumarate is prescribed with ritonavir. Renal function should be monitored regularly, including surveillance for signs of tubulopathy such as glycosuria, acidosis, increases in serum creatinine level, electrolyte disturbances (e.g., hypokalemia, hypophosphatemia), and proteinuria. The same precaution may be applicable during therapy with other protease inhibitors based on their similar pharmacokinetic profile, although clinical data are lacking. Nelfinavir reportedly does not alter the pharmacokinetics of tenofovir, or vice versa. Tenofovir administration should be discontinued promptly if nephropathy develops.

References (8)
  1. (2001) "Product Information. Viread (tenofovir)." Gilead Sciences
  2. Verhelst D, Monge M, Meynard JL, et al. (2002) "Fanconi syndrome and renal failure induced by tenofovir: A first case report." Am J Kidney Dis, 40, p. 1331-3
  3. Creput C, Gonzalez-Canali G, Hill G, Piketty C, Kazatchkine M, Nochy D (2003) "Renal lesions in HIV-1-positive patient treated with tenofovir." AIDS, 17, p. 935-7
  4. Karras A, Lafaurie M, Furco A, et al. (2003) "Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, fanconi syndrome, and nephrogenic diabetes insipidus." Clin Infect Dis, 36, p. 1070-3
  5. Kearney BP, Mittan A, Sayre J, et al. (2003) Pharmacokinetic drug interaction and long term safety profile of tenofovir DF and lopinavir/ritonavir. http://www.icaac.org/ICAAC.asp
  6. Rollot F, Nazal EM, Chauvelot-Moachon L, et al. (2003) "Tenofovir-related fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: the role of lopinavir-ritonavir-Didanosine." Clin Infect Dis, 37, E174-6
  7. Zimmermann AE, Pizzoferrato T, Bedford J, Morris A, Hoffman R, Braden G (2006) "Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions." Clin Infect Dis, 42, p. 283-90
  8. Kapadia J, Shah S, Desai C, et al. (2013) "Tenofovir induced Fanconi syndrome: a possible pharmacokinetic interaction." Indian J Pharmacol, 45, p. 191-2

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Moderate

ritonavir vilanterol

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir disoproxil and fluticasone / umeclidinium / vilanterol

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the systemic exposure to vilanterol following oral inhalation, as it is primarily metabolized by the isoenzyme. The interaction has been studied with fluticasone-vilanterol and ketoconazole. When fluticasone-vilanterol (200 mcg-25 mcg once daily for 7 days) was coadministered with ketoconazole (400 once daily for 11 days) in healthy subjects, fluticasone and vilanterol systemic exposure (AUC) were 36% and 65% higher, respectively, compared to coadministration with placebo. The increase in fluticasone exposure was associated with a 27% reduction in 24-hour weighted mean serum cortisol, whereas the increase in vilanterol exposure was not associated with an increase in beta-2 adrenergic systemic effects on heart rate or blood potassium.

MANAGEMENT: Due to the risk of cardiovascular adverse effects such as increases in pulse rate and blood pressure and ECG changes such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression, caution is recommended when medications containing vilanterol are coadministered with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics. An increased risk of systemic corticosteroid effects should also be considered when fluticasone-vilanterol is used.

References (3)
  1. (2013) "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline
  2. Kempsford R, Norris V, Siederer S (2013) "Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD." Pulm Pharmacol Ther, 26, p. 256-64
  3. (2022) "Product Information. Anoro Ellipta (umeclidinium-vilanterol)." GlaxoSmithKline

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Moderate

lopinavir tenofovir

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir disoproxil and emtricitabine / lopinavir / ritonavir / tenofovir disoproxil

MONITOR: Coadministration with ritonavir, with or without lopinavir, has been suggested in postmarketing reports to increase the proximal tubular intracellular concentrations of tenofovir and potentiate the risk of tenofovir-induced nephrotoxicity. The proposed mechanism is ritonavir inhibition of tenofovir renal tubular secretion into the urine via multidrug resistance protein MRP2. Analysis of data from a compassionate access study in which 271 patients with advanced HIV disease received the combination for a mean duration of 63 weeks revealed no clinically significant nephrotoxicity associated with coadministration. However, there have been case reports of renal failure associated with acute tubular necrosis, Fanconi's syndrome, and nephrogenic diabetes insipidus in patients treated with tenofovir disoproxil fumarate in combination with ritonavir. Some patients had incomplete recovery of renal function more than a year after cessation of tenofovir therapy. Ritonavir given in combination with lopinavir has also been reported to modestly increase the plasma concentrations of tenofovir. In contrast, both slight decreases and no change in lopinavir and ritonavir concentrations have been reported.

MANAGEMENT: Caution is advised if tenofovir disoproxil fumarate is prescribed with ritonavir. Renal function should be monitored regularly, including surveillance for signs of tubulopathy such as glycosuria, acidosis, increases in serum creatinine level, electrolyte disturbances (e.g., hypokalemia, hypophosphatemia), and proteinuria. The same precaution may be applicable during therapy with other protease inhibitors based on their similar pharmacokinetic profile, although clinical data are lacking. Nelfinavir reportedly does not alter the pharmacokinetics of tenofovir, or vice versa. Tenofovir administration should be discontinued promptly if nephropathy develops.

References (8)
  1. (2001) "Product Information. Viread (tenofovir)." Gilead Sciences
  2. Verhelst D, Monge M, Meynard JL, et al. (2002) "Fanconi syndrome and renal failure induced by tenofovir: A first case report." Am J Kidney Dis, 40, p. 1331-3
  3. Creput C, Gonzalez-Canali G, Hill G, Piketty C, Kazatchkine M, Nochy D (2003) "Renal lesions in HIV-1-positive patient treated with tenofovir." AIDS, 17, p. 935-7
  4. Karras A, Lafaurie M, Furco A, et al. (2003) "Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, fanconi syndrome, and nephrogenic diabetes insipidus." Clin Infect Dis, 36, p. 1070-3
  5. Kearney BP, Mittan A, Sayre J, et al. (2003) Pharmacokinetic drug interaction and long term safety profile of tenofovir DF and lopinavir/ritonavir. http://www.icaac.org/ICAAC.asp
  6. Rollot F, Nazal EM, Chauvelot-Moachon L, et al. (2003) "Tenofovir-related fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: the role of lopinavir-ritonavir-Didanosine." Clin Infect Dis, 37, E174-6
  7. Zimmermann AE, Pizzoferrato T, Bedford J, Morris A, Hoffman R, Braden G (2006) "Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions." Clin Infect Dis, 42, p. 283-90
  8. Kapadia J, Shah S, Desai C, et al. (2013) "Tenofovir induced Fanconi syndrome: a possible pharmacokinetic interaction." Indian J Pharmacol, 45, p. 191-2

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Moderate

lopinavir vilanterol

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir disoproxil and fluticasone / 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 (30)
  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

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Minor

fluticasone vilanterol

Applies to: fluticasone / umeclidinium / vilanterol and fluticasone / umeclidinium / vilanterol

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.

References (4)
  1. (2001) "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html

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Drug and food interactions

Moderate

ritonavir food

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir disoproxil

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References (1)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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Moderate

lopinavir food

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir disoproxil

ADJUST DOSING INTERVAL: Food significantly increases the bioavailability of lopinavir from the oral solution formulation of lopinavir-ritonavir. Relative to fasting, administration of lopinavir-ritonavir oral solution with a moderate-fat meal (500 to 682 Kcal; 23% to 25% calories from fat) increased lopinavir peak plasma concentration (Cmax) and systemic exposure (AUC) by 54% and 80%, respectively, whereas administration with a high-fat meal (872 Kcal; 56% from fat) increased lopinavir Cmax and AUC by 56% and 130%, respectively. No clinically significant changes in Cmax and AUC were observed following administration of lopinavir-ritonavir tablets under fed conditions versus fasted conditions. Relative to fasting, administration of a single 400 mg-100 mg dose (two 200 mg-50 mg tablets) with a moderate-fat meal (558 Kcal; 24.1% calories from fat) increased lopinavir Cmax and AUC by 17.6% and 26.9%, respectively, while administration with a high-fat meal (998 Kcal; 51.3% from fat) increased lopinavir AUC by 18.9% but not Cmax. Relative to fasting, ritonavir Cmax and AUC also increased by 4.9% and 14.9%, respectively, with the moderate-fat meal and 10.3% and 23.9%, respectively, with the high-fat meal.

MANAGEMENT: Lopinavir-ritonavir oral solution should be taken with meals to enhance bioavailability and minimize pharmacokinetic variability. Lopinavir-ritonavir tablets may be taken without regard to meals.

References (1)
  1. (2001) "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical

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Minor

tenofovir food

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir disoproxil

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)
  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.