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Drug Interactions between doxazosin and Stribild

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

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Interactions between your drugs

Moderate

doxazosin cobicistat

Applies to: doxazosin and Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir)

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations and effects of doxazosin. In vitro studies suggest that the primary pathway for elimination of doxazosin is via CYP450 3A4.

MANAGEMENT: Caution is advised if doxazosin is used concomitantly with potent CYP450 3A4 inhibitors. Blood pressure and pharmacologic response to doxazosin should be monitored closely whenever a potent CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the doxazosin dosage adjusted if necessary. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medication affects them.

References

  1. (2001) "Product Information. Cardura (doxazosin)." Pfizer U.S. Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink

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Moderate

tenofovir cobicistat

Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir) and Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir)

MONITOR: Concomitant use of tenofovir with cobicistat may increase the risk for tenofovir-related renal adverse effects, including renal impairment, renal failure, elevated creatinine, and Fanconi syndrome. The mechanism of this interaction has not been described. Cobicistat may decrease estimated creatinine clearance via inhibition of tubular secretion of creatinine; however, renal glomerular function does not appear to be affected. When given concomitantly with cobicistat, the systemic exposure (AUC) and trough plasma concentrations (Cmin) of tenofovir was also increased by 23% and 55%, respectively. However, data are lacking to determine whether concomitant use of tenofovir with cobicistat-containing regimens is associated with a greater risk of renal complications compared with regimens that do not include cobicistat.

MANAGEMENT: Initiation of cobicistat or cobicistat-containing regimens is not recommended in patients with CrCl less than 70 mL/min if any coadministered medicine requires dose adjustment based on renal function (including tenofovir), or is nephrotoxic. If concomitant therapy is necessary, monitoring of renal function is recommended, particularly in patients with risk factors for renal impairment.

References

  1. (2001) "Product Information. Viread (tenofovir)." Gilead Sciences
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2014) "Product Information. Tybost (cobicistat)." Gilead Sciences
View all 4 references

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Moderate

emtricitabine cobicistat

Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir) and Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir)

GENERALLY AVOID: Cobicistat may increase the plasma concentrations of antiretroviral agents. The plasma concentrations of cobicistat may also be increased or reduced in the presence of antiretroviral agents. The proposed mechanism is cobicistat inhibition of the CYP450 3A4 isoenzyme, of which antiretroviral agents may be substrates, and the inhibition or induction of CYP450 3A4 by concomitant antiretroviral medications. Cobicistat is a mechanism-based inhibitor and substrate of CYP450 3A4 with no antiretroviral activity of its own. Rather, it is indicated in its capacity as a pharmacokinetic booster of CYP450 3A4 to increase the systemic exposure of some antiretroviral medications such as atazanavir, darunavir, and elvitegravir, which are substrates of this isoenzyme. Concomitant use of other antiretroviral agents with cobicistat may also increase the plasma levels and risk of side effects associated with these medicines. In contrast, concomitant use of cobicistat-boosted atazanavir or darunavir with CYP450 3A4 inducers nevirapine, etravirine, or efavirenz may reduce the plasma concentrations of cobicistat, darunavir, and atazanavir, leading to a potential loss of therapeutic effect and development of resistance to darunavir and atazanavir. Pharmacokinetic data are not available.

MANAGEMENT: Cobicistat is not intended for use with more than one antiretroviral medication that requires pharmacokinetic enhancement, such as two protease inhibitors or elvitegravir in combination with a protease inhibitor. In addition, cobicistat should not be used concomitantly with ritonavir due to their similar effects on CYP450 3A4. According to some authorities, use of the antiretroviral combinations of atazanavir-cobicistat or darunavir-cobicistat concomitantly with the CYP450 3A4 inducers efavirenz, etravirine, or nevirapine is also not recommended. Other authorities consider the administration of atazanavir-cobicistat with efavirenz or nevirapine to be contraindicated. Since dosing recommendations have only been established for a number of antiretroviral medications, product labeling and current antiretroviral treatment guidelines should be consulted.

References

  1. (2001) "Product Information. Viramune (nevirapine)." Boehringer-Ingelheim
  2. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  5. (2008) "Product Information. Intelence (etravirine)." Ortho Biotech Inc
  6. Cerner Multum, Inc. "Australian Product Information."
  7. (2012) "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences
  8. (2014) "Product Information. Tybost (cobicistat)." Gilead Sciences
  9. (2014) "Product Information. Prezcobix (cobicistat-darunavir)." Janssen Pharmaceuticals
  10. (2015) "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb
View all 10 references

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Drug and food interactions

Moderate

elvitegravir food

Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailabilities of both elvitegravir and tenofovir. When a single dose of cobicistat/elvitegravir/emtricitabine/tenofovir (trade name Stribild) was given with a light meal (approximately 373 kcal; 20% fat), mean elvitegravir and tenofovir systemic exposures (AUCs) increased by 34% and 24%, respectively, relative to fasting conditions. When administered with a high-fat meal (approximately 800 kcal; 50% fat), the mean AUC of elvitegravir and tenofovir increased by 87% and 23%, respectively, relative to fasting conditions. The alterations in mean AUCs of cobicistat and emtricitabine were not clinically significant with either the light or high-fat meal.

MANAGEMENT: Cobicistat/elvitegravir/emtricitabine/tenofovir as a fixed-dose preparation should be administered once daily with food. Elvitegravir as a single-ingredient preparation should also be administered once daily with food.

References

  1. (2012) "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences
  2. (2014) "Product Information. Vitekta (elvitegravir)." Gilead Sciences

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Moderate

doxazosin food

Applies to: doxazosin

GENERALLY AVOID: The concurrent use of ethanol and alpha-1 adrenergic blockers may cause increased hypotensive effects. Patients with aldehyde dehydrogenase deficiencies (primarily Asians) may be at a higher risk of this interaction. The mechanism has not been determined. Data exist for prazosin and other alpha adrenergic blockers are expected to interact also. In addition, any patients taking alpha adrenergic blockers may experience excessive orthostatic hypotension with ethanol ingestion, due to ethanol's unopposed vasodilatory effects in the presence of alpha adrenergic blockade.

MANAGEMENT: Patients who develop a flushing reaction after ethanol ingestion (indicates a possible aldehyde dehydrogenase deficiency) should be advised to avoid ethanol or limit their intake. All patients should be warned about the possibility of orthostatic hypotension with concurrent ethanol use.

References

  1. Kawano Y, Abe H, Kojima S, Takishita S, Omae T (2000) "Interaction of alcohol and an a1-blocker on ambulatory blood pressure in patients with essential hypertension." Am J Hypertens, 13, p. 307-12
  2. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc

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Minor

tenofovir food

Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / 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. (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.