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Drug Interactions between emtricitabine / rilpivirine / tenofovir alafenamide and ProAir RespiClick

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

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Interactions between your drugs

Moderate

albuterol rilpivirine

Applies to: ProAir RespiClick (albuterol) and emtricitabine / rilpivirine / tenofovir alafenamide

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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Drug and food interactions

Moderate

rilpivirine food

Applies to: emtricitabine / rilpivirine / tenofovir alafenamide

GENERALLY AVOID: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of rilpivirine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. In 15 study subjects given rilpivirine (150 mg once daily) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), mean rilpivirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) were increased by 30%, 49% and 76%, respectively. In 16 study subjects given a single 500 mg dose of a less potent CYP450 3A4 inhibitor chlorzoxazone two hours after rilpivirine (150 mg once daily), mean rilpivirine Cmax, AUC, and Cmin were increased by 17%, 25%, and 18%, respectively. 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.

ADJUST DOSING INTERVAL: The administration of rilpivirine in a fasting state may decrease its oral absorption. Under fasted conditions, the systemic exposure to rilpivirine was 40% lower compared to normal or high-fat caloric meals (533 to 928 Kcal). The systemic exposure was 50% lower when rilpivirine was taken with a protein-rich nutritional beverage.

MANAGEMENT: Coadministration of grapefruit or grapefruit juice with rilpivirine should preferably be avoided. For optimal absorption, it is recommended to take rilpivirine on a regular schedule with a meal.

References

  1. "Product Information. Edurant (rilpivirine)." Tibotec Pharmaceuticals (2011):
  2. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):

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Moderate

albuterol food

Applies to: ProAir RespiClick (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 / rilpivirine / tenofovir alafenamide

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.

See also

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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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