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Drug Interactions between emtricitabine / lopinavir / ritonavir / tenofovir and Ventolin HFA

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

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Interactions between your drugs

Moderate

albuterol lopinavir

Applies to: Ventolin HFA (albuterol) and emtricitabine / lopinavir / ritonavir / tenofovir

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

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Moderate

ritonavir tenofovir

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

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

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

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Moderate

lopinavir tenofovir

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

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

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

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Drug and food interactions

Moderate

ritonavir food

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir

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. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

lopinavir food

Applies to: emtricitabine / lopinavir / ritonavir / tenofovir

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. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

albuterol food

Applies to: Ventolin HFA (albuterol)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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Minor

tenofovir food

Applies to: emtricitabine / lopinavir / ritonavir / 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. "Product Information. Viread (tenofovir)." Gilead Sciences (2001):

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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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