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Drug Interactions between emtricitabine / rilpivirine / tenofovir and iohexol

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

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Interactions between your drugs

Major

iohexol tenofovir

Applies to: iohexol and emtricitabine / rilpivirine / tenofovir

GENERALLY AVOID: Concomitant use of intravascular radiocontrast media with other nephrotoxic agents may potentiate the risk of contrast-induced nephropathy and renal impairment. Contrast-induced nephropathy is most commonly defined as an increase in serum creatinine >=0.5 mg/dL or 25% from baseline within 24 to 72 hours of intravascular contrast administration in the absence of alternative etiologies, although nephropathy may occur up to a week after contrast exposure. Pathogenesis has not been fully elucidated, but may involve renal hypoperfusion and ischemia, direct cytotoxicity on tubular epithelial cells, and generation of reactive oxygen species. While the condition is usually transient and asymptomatic, it can be associated with increased risk of renal failure, dialysis, prolonged hospitalization, significant long-term morbidity, and mortality. Patients at increased risk of developing contrast-induced nephropathy include those with diabetes (especially diabetic nephropathy), preexisting renal insufficiency (serum creatinine >1.5 mg/dL or GFR <60 mL/min/1.73 m2), volume depletion (e.g., diuretic use), advanced age (>70 years), congestive heart failure, multiple myeloma, hypoalbuminemia, and concomitant use of nephrotoxic agents (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; aminosalicylates; antiviral/antiretroviral agents such as acyclovir, adefovir, cidofovir, foscarnet, and tenofovir; antineoplastics such as aldesleukin, cisplatin, clofarabine, ifosfamide, streptozocin, and high intravenous dosages of methotrexate; chelating agents such as deferasirox, deferoxamine, edetate disodium, and edetate calcium disodium; immunosuppressants such as cyclosporine, everolimus, sirolimus, and tacrolimus; intravenous bisphosphonates; intravenous pentamidine; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents; gallium nitrate; lithium; penicillamine). The incidence has been reported to be approximately 10% to 30% in patients with risk factors, and as high as 90% in diabetics with chronic kidney disease. Intraarterial administration of contrast media is also associated with increased risk of nephropathy relative to intravenous administration.

MANAGEMENT: Alternative imaging techniques that do not require contrast should be considered in patients who are at increased risk for contrast-induced nephropathy. Otherwise, experts recommend discontinuing other nephrotoxic drugs 1 to 2 days before administration of contrast media, depending on the clinical feasibility of doing so. The smallest effective dose (100 mL or less) of a nonionic, low-osmolar (e.g., iohexol, iomeprol, iopamidol, iopental, iopromide, ioversol) or iso-osmolar (e.g., iodixanol, iotrolan) contrast medium should be used whenever possible, since the risk of nephrotoxicity may be increased with increasing contrast dose, osmolarity, and ionicity. Some studies suggest a lower risk for iso-osmolar contrasts compared to low-osmolar contrasts, although data are limited. Serum creatinine levels should be measured before contrast administration (if procedure is not urgent) and continued for 24 to 48 hours after. In addition, patients should be adequately hydrated with either intravenous normal saline or sodium bicarbonate starting 3 (outpatient) to 6 (inpatient) hours before and continued for 6 to 24 hours after procedure. Oral fluids are also beneficial, but not as effective as intravenous hydration. N-acetylcysteine the day before and day of contrast administration, or theophylline up to 30 minutes before contrast administration, have also been used in high-risk or critically ill patients. Preferably, a nephrologist should be consulted to optimize prophylactic measures for preventing contrast-induced nephropathy in high-risk patients and to guide treatment if the condition occurs. Any repeat procedures with contrast media, if necessary, should not occur until at least 48 to 72 hours after the previous contrast exposure and renal function has fully recovered.

References

  1. Bennett WM, Porter GA "Nephrotoxicity of common drugs used by urologists." Urol Clin North Am 17 (1990): 145-56
  2. Bentley ML, Corwin HL, Dasta J "Drug-induced acute kidney injury in the critically ill adult: recognition and prevention strategies." Crit Care Med 38(6 Suppl) (2010): S169-74
  3. Marcos LA, Camins BC, Ritchie DJ, Casabar E, Warren DK "Acute renal insufficiency during telavancin therapy in clinical practice." J Antimicrob Chemother 67 (2012): 723-6
  4. Dubrovskaya Y, Prasad N, Lee Y, Esaian D, Figueroa DA, Tam VH "Risk factors for nephrotoxicity onset associated with polymyxin B therapy." J Antimicrob Chemother 70 (2015): 1903-7
  5. Bansal R, Aflieco F, Kaplan AA "Contrast-Induced Nephropathy. http://emedicine.medscape.com/article/246751-overview" (2016):
  6. van den Berk G, Tonino S, de Fijter C, Smit W, Schultz MJ "Bench-to-bedside review: Preventative measures for contrast-induced nephropathy in critically ill patients." Crit Care 9 (2005): 361-70
  7. Kellum JA, Leblanc M, Venkataraman R "Acute renal failure." BMJ Clin Evid 9 (2008): 2001
View all 7 references

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Drug and food interactions

Moderate

rilpivirine food

Applies to: emtricitabine / rilpivirine / tenofovir

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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Minor

tenofovir food

Applies to: emtricitabine / rilpivirine / 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.