Drug News
Dolutegravir (Tivicay) for HIV infection By Danielle N. Rhyne, PharmD; Emily S. Byrd, PharmD; and Olga M. Klibanov, PharmD, BCPS
Over the past 3 decades, the treatment of HIV-infected patients has evolved significantly with advances in antiretroviral (ARV) therapies, leading to dramatic increases in life expectancy. Dolutegravir (Tivicay) belongs to the integrase strand transfer inhibitor (INSTI) class of ARV drugs and is the latest addition to the ARV armamentarium. Raltegravir (Isentress), the first FDA-approved HIV integrase inhibitor, is effective and well tolerated, but requires twice-daily dosing. Elvitegravir is another potent integrase inhibitor, but this drug needs pharmacologic boosting, which can result in significant drug-drug interactions. Additionally, elvitegravir is currently only available as a coformulated product with cobicistat, emtricitabine, and tenofovir (Stribild). These first-generation integrase inhibitors have relatively low thresholds for resistance development and share resistance pathways; therefore, if a patient becomes resistant to one of them, it is unlikely that the other drug will be effective.1 Dolutegravir is a second-generation integrase inhibitor that offers another option for treating HIV-infected individuals.2 This agent does not require pharmacologic boosting, can be administered once daily in certain patients, and has a higher barrier for resistance compared with first-generation integrase inhibitors.3 It can also be used in some patients who www.tnpj.com
have acquired integrase resistance from previous raltegravir or elvitegravir therapy. Dolutegravir was studied in several Phase III clinical trials (SPRING-2, SINGLE, SAILING, VIKING-3) involving over 2,500 HIV-infected patients and was compared with other standard HIV treatments.4-7 The drug was found to be effective and safe in these large clinical trials, which led to its FDA approval in August 2013. Dolutegravir is marketed and manufactured by GlaxoSmithKline (ViiV Healthcare). ■ Indication Dolutegravir is indicated for the treatment of HIV-1 infection in combination with other ARV
Recommended dolutegravir dosing).2 The dosing frequency depends on whether the patient is treatment-naive (for example, no previous ARV exposure) or treatment-experienced (for example, prior ARV exposure); whether they have been on a firstgeneration integrase inhibitor in the past; whether they have a history of resistance to integrase inhibitors; or whether there are interacting medications in the patient’s regimen.2 In patients with renal and hepatic impairment, dosage adjustments are not necessary; however, dolutegravir is not recommended in patients with severe hepatic impairment because data are lacking in this specific population. Dolutegravir may be taken without regard to meals, and it should
Dolutegravir offers another option for treating HIV-infected individuals. medications in adults and children ages 12 years and older who weigh at least 40 kg.2 ■ Mechanism of action Dolutegravir is an INSTI. This agent blocks the action of HIV integrase by binding to the integrase active site and inhibiting the HIV-1 DNA integration step of strand transfer. Strand transfer is critical for the HIV replication process.2 ■ Dosing and administration The dose of dolutegravir is either 50 mg once or twice daily depending on several patient-specific factors (see
be taken 2 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.2 ■ Contraindications Dolutegravir is contraindicated in patients taking dofetilide (Tikosyn). Concurrent use of these two medications may increase dofetilide plasma concentrations, leading to possible serious and/or life-threatening events.2 ■ Warnings and precautions Upon initiation of dolutegravir, patients should be monitored for The Nurse Practitioner • June 2014 11
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Drug News
hypersensitivity reactions, which can present as a rash with the following: fever, malaise, fatigue, muscle/joint aches, blisters or peeling skin, oral blisters/lesions, conjunctivitis, facial edema, angioedema, difficulty breathing, or organ dysfunction including liver injury. In Phase III clinical trials, less than 1% of patients reported these reactions; however, patients who present with these reactions should discontinue therapy with dolutegravir.2 Patients with underlying hepatitis B or C may have an increased risk for elevations in transaminase levels when using dolutegravir. Studies found that most elevations occurred in patients with immune reconstitution syndrome or hepatitis B reactivation when therapy was withdrawn. As a result, patients with underlying hepatic disease should have baseline hepatic monitoring as well as monitoring during treatment with dolutegravir. Dolutegravir is not recommended for use in patients with severe hepatic impairment.2
Fat redistribution and/or accumulation have been observed in patients receiving ARV therapy. The SPRING-2 and SINGLE trials reported changes from baseline in cholesterol, highdensity lipoprotein, low-density lipoprotein, and triglycerides.5,6 As a result, patients should have their lipids and glucose levels monitored throughout therapy. Furthermore, prescribers may want to consider initiating a lipid-lowering agent in patients who have increased lipid levels. Immune reconstitution syndrome can occur in patients receiving combination ARV therapy. These signs and symptoms usually occur when therapy is initiated. As a result, patients who have had opportunistic infections in the past should be monitored. Additionally, reports of autoimmune disorders (Guillain-Barré, Graves disease, and polymyositis) in the setting of immune reconstitution were also reported.2 Use of dolutegravir in pregnant women has not been studied; however, animal studies showed
Recommended dolutegravir dosing2 Adult population
Recommended dose
Treatment-naive or treatment-experienced (but INSTI-naive)
50 mg once daily
Treatment-naive or treatment-experienced (but INSTI-naive), when coadministered with efavirenz, fosamprenavir/ritonavir, tipranavir/ ritonavir, or rifampin
50 mg twice daily
INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance
50 mg twice daily
Pediatric population (age 12 years and older, at least 40 kg)
Recommended dose
Treatment-naive or treatment-experienced (but INSTI-naive)
50 mg once daily
Treatment-naive or treatment-experienced (but INSTI-naive), when coadministered with efavirenz, fosamprenavir/ritonavir, tipranavir/ ritonavir, or rifampin
50 mg twice daily
no harm to the fetus, but did cross the placenta. Dolutegravir is rated pregnancy category B, but should be used during pregnancy only if needed.2 An ARV pregnancy registry has been established to monitor fetal outcomes of pregnant women with HIV exposed to dolutegravir. Healthcare professionals are encouraged to register any woman who is on dolutegravir during pregnancy with the Antiretroviral Pregnancy Registry (1-800-258-4263). The CDC recommends that HIV-positive mothers in the United States not breast feed their infants to avoid the risk of HIV transmission.8 It is not known whether dolutegravir is excreted in breast milk in lactating women. Due to the risk of HIV transmission and the unknown effect on the infant if the mother is taking dolutegravir, mothers should be instructed to avoid breastfeeding.2 ■ Adverse reactions Dolutegravir is a well-tolerated ARV. The most common adverse reactions seen in any trial for patients receiving dolutegravir were insomnia and headache, with an incidence of 2% to 3%. Other documented adverse reactions occurring in less than 2% of treatment-naive or treatmentexperienced patients included diarrhea, abdominal pain, nausea, vomiting, fatigue, pruritus, and increased serum lipase levels.2,4-7 ■ Drug interactions Dofetilide is the main drug-drug interaction to keep in mind with dolutegravir. Coadministration of dofetilide with dolutegravir is contraindicated due to possible increases in dofetilide concentrations and the risk of serious and/or lifethreatening events, such as ventricular dysrhythmias and QT interval prolongation.2
12 The Nurse Practitioner • Vol. 39, No. 6
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.tnpj.com
Drug News Concentrations of dolutegravir are decreased in the presence of another ARV drug, etravirine. These two drugs should not be coadministered unless the patient is also on either atazanavir/ ritonavir, darunavir/ritonavir, or lopinavir/ritonavir, as these drugs mitigate that interaction.2 Dolutegravir concentrations are also decreased in the presence of rifampin, efavirenz, fosamprenavir/ ritonavir, and tipranavir/ritonavir. The dose of dolutegravir should be adjusted when it is coadministered with these agents.2 Due to insufficient pharmacokinetic data to make dosing recommendations, it is currently recommended to avoid coadministering dolutegravir with the following medications: nevirapine, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, and St. John’s wort. These recommendations may change as more clinical pharmacokinetic studies are performed with dolutegravir.2 Medications containing cations (for example, magnesium, aluminum, iron, or calcium) can decrease the levels of dolutegravir. Therefore, if the patient is also taking cation-containing antacids, laxatives, sucralfate, oral iron, calcium supplements, or buffered medications, dolutegravir should be taken 2 hours before or 6 hours after these medications.2 (See Patient counseling points.) Dolutegravir can also increase concentrations of metformin. It is recommended to closely monitor patients when starting or stopping these medications and to adjust the dose of metformin as necessary.2 ■ Pharmacokinetics The extent of dolutegravir absorption increases with food while the rate of absorption is decreased. It can be taken with or without food. Peak plasma concentrations of www.tnpj.com
Patient counseling points2 • Tivicay should always be used with other medications that treat HIV • Do not take Tivicay if you take dofetilide, as this combination may be life-threatening • Before taking Tivicay, tell your healthcare provider if you: – have or had liver problems, including hepatitis B or C infection – are pregnant or plan to become pregnant – are breastfeeding or plan to breast-feed. Do not breast-feed if you are infected with HIV. • Tell your healthcare provider about other medications you take, including prescription and over-the-counter drugs, vitamins, or herbal supplements • Tivicay can be taken with or without food • The most common adverse reactions of Tivicay include trouble sleeping and headache
dolutegravir occur 2 to 3 hours after oral administration. When the drug is given once daily, the steady state of dolutegravir is achieved within 5 days.2 Dolutegravir is primarily bound (greater than or equal to 98.9%) to human plasma proteins. It is mostly metabolized by glucuronidation (via UGT1A1), with some contribution from CYP3A. The drug is mainly excreted unchanged in the feces (53%), and other inactive metabolites are excreted in the urine. Renal elimination of unchanged drug is minimal (less than 1%); therefore, dolutegravir dosing adjustments in renal impairment are not needed.2 ■ Clinical pearls • Dolutegravir provides an effective, well-tolerated addition to the integrase inhibitor class of ARV medications. • Dolutegravir is pregnancy category B and should only be used in pregnant women if benefits outweigh the risks. • The most common adverse reactions seen with dolutegravir in clinical trials were insomnia and headache, occurring in only 2% to 3% of patients. • The dosing of dolutegravir depends on the patient’s HIV treatment history and concomitant medications.
REFERENCES 1. STRIBILD [package insert]. Foster City, CA: Gilead Sciences; 2013. 2. TIVICAY [package insert]. Research Triangle Park, NC: GlaxoSmithKline (ViiV Healthcare); 2013. 3. Messiaen P, Wensing AM, Fun A, Nijhuis M, Brusselaers N, Vandekerckhove L. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One. 2013;8(1):e52562. 4. Cahn P, Pozniak AL, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviralexperienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700-708. 5. Raffi F, Rachlis A, Stellbrink HJ, et al. Once-daily dolutegravir versus raltegravir in antiretroviralnaive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013;381(9868):735-743. 6. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807-1818. 7. Nichols G, Mills A, Grossberg R, et al. Antiviral activity of dolutegravir in subjects with failure on an integrase inhibitor-based regimen: week 24 phase 3 results from VIKING-3. Journal of the International AIDS Society. 2012;15(suppl 4):18112. 8. The Centers for Disease Control and Prevention. http://www.cdc.gov/breastfeeding/disease/ index.htm.
Danielle N. Rhyne is a pharmacy resident at the University of Colorado, Aurora, Colo. Emily S. Byrd is a doctorate of pharmacy candidate at Wingate University, Wingate, N.C. Olga M. Klibanov is an associate professor of pharmacy at Wingate University, Wingate, N.C.
The authors have disclosed that they have no financial relationships related to this article.
DOI-10.1097/01.NPR.0000444657.88872.7f
The Nurse Practitioner • June 2014 15
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Dolutegravir (Tivicay) for HIV infection By Danielle N. Rhyne, PharmD; Emily S. Byrd, PharmD; and Olga M. Klibanov, PharmD, BCPS
Over the past 3 decades, the treatment of HIV-infected patients has evolved significantly with advances in antiretroviral (ARV) therapies, leading to dramatic increases in life expectancy. Dolutegravir (Tivicay) belongs to the integrase strand transfer inhibitor (INSTI) class of ARV drugs and is the latest addition to the ARV armamentarium. Raltegravir (Isentress), the first FDA-approved HIV integrase inhibitor, is effective and well tolerated, but requires twice-daily dosing. Elvitegravir is another potent integrase inhibitor, but this drug needs pharmacologic boosting, which can result in significant drug-drug interactions. Additionally, elvitegravir is currently only available as a coformulated product with cobicistat, emtricitabine, and tenofovir (Stribild). These first-generation integrase inhibitors have relatively low thresholds for resistance development and share resistance pathways; therefore, if a patient becomes resistant to one of them, it is unlikely that the other drug will be effective.1 Dolutegravir is a second-generation integrase inhibitor that offers another option for treating HIV-infected individuals.2 This agent does not require pharmacologic boosting, can be administered once daily in certain patients, and has a higher barrier for resistance compared with first-generation integrase inhibitors.3 It can also be used in some patients who www.tnpj.com
have acquired integrase resistance from previous raltegravir or elvitegravir therapy. Dolutegravir was studied in several Phase III clinical trials (SPRING-2, SINGLE, SAILING, VIKING-3) involving over 2,500 HIV-infected patients and was compared with other standard HIV treatments.4-7 The drug was found to be effective and safe in these large clinical trials, which led to its FDA approval in August 2013. Dolutegravir is marketed and manufactured by GlaxoSmithKline (ViiV Healthcare). ■ Indication Dolutegravir is indicated for the treatment of HIV-1 infection in combination with other ARV
Recommended dolutegravir dosing).2 The dosing frequency depends on whether the patient is treatment-naive (for example, no previous ARV exposure) or treatment-experienced (for example, prior ARV exposure); whether they have been on a firstgeneration integrase inhibitor in the past; whether they have a history of resistance to integrase inhibitors; or whether there are interacting medications in the patient’s regimen.2 In patients with renal and hepatic impairment, dosage adjustments are not necessary; however, dolutegravir is not recommended in patients with severe hepatic impairment because data are lacking in this specific population. Dolutegravir may be taken without regard to meals, and it should
Dolutegravir offers another option for treating HIV-infected individuals. medications in adults and children ages 12 years and older who weigh at least 40 kg.2 ■ Mechanism of action Dolutegravir is an INSTI. This agent blocks the action of HIV integrase by binding to the integrase active site and inhibiting the HIV-1 DNA integration step of strand transfer. Strand transfer is critical for the HIV replication process.2 ■ Dosing and administration The dose of dolutegravir is either 50 mg once or twice daily depending on several patient-specific factors (see
be taken 2 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.2 ■ Contraindications Dolutegravir is contraindicated in patients taking dofetilide (Tikosyn). Concurrent use of these two medications may increase dofetilide plasma concentrations, leading to possible serious and/or life-threatening events.2 ■ Warnings and precautions Upon initiation of dolutegravir, patients should be monitored for The Nurse Practitioner • June 2014 11
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Drug News
hypersensitivity reactions, which can present as a rash with the following: fever, malaise, fatigue, muscle/joint aches, blisters or peeling skin, oral blisters/lesions, conjunctivitis, facial edema, angioedema, difficulty breathing, or organ dysfunction including liver injury. In Phase III clinical trials, less than 1% of patients reported these reactions; however, patients who present with these reactions should discontinue therapy with dolutegravir.2 Patients with underlying hepatitis B or C may have an increased risk for elevations in transaminase levels when using dolutegravir. Studies found that most elevations occurred in patients with immune reconstitution syndrome or hepatitis B reactivation when therapy was withdrawn. As a result, patients with underlying hepatic disease should have baseline hepatic monitoring as well as monitoring during treatment with dolutegravir. Dolutegravir is not recommended for use in patients with severe hepatic impairment.2
Fat redistribution and/or accumulation have been observed in patients receiving ARV therapy. The SPRING-2 and SINGLE trials reported changes from baseline in cholesterol, highdensity lipoprotein, low-density lipoprotein, and triglycerides.5,6 As a result, patients should have their lipids and glucose levels monitored throughout therapy. Furthermore, prescribers may want to consider initiating a lipid-lowering agent in patients who have increased lipid levels. Immune reconstitution syndrome can occur in patients receiving combination ARV therapy. These signs and symptoms usually occur when therapy is initiated. As a result, patients who have had opportunistic infections in the past should be monitored. Additionally, reports of autoimmune disorders (Guillain-Barré, Graves disease, and polymyositis) in the setting of immune reconstitution were also reported.2 Use of dolutegravir in pregnant women has not been studied; however, animal studies showed
Recommended dolutegravir dosing2 Adult population
Recommended dose
Treatment-naive or treatment-experienced (but INSTI-naive)
50 mg once daily
Treatment-naive or treatment-experienced (but INSTI-naive), when coadministered with efavirenz, fosamprenavir/ritonavir, tipranavir/ ritonavir, or rifampin
50 mg twice daily
INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance
50 mg twice daily
Pediatric population (age 12 years and older, at least 40 kg)
Recommended dose
Treatment-naive or treatment-experienced (but INSTI-naive)
50 mg once daily
Treatment-naive or treatment-experienced (but INSTI-naive), when coadministered with efavirenz, fosamprenavir/ritonavir, tipranavir/ ritonavir, or rifampin
50 mg twice daily
no harm to the fetus, but did cross the placenta. Dolutegravir is rated pregnancy category B, but should be used during pregnancy only if needed.2 An ARV pregnancy registry has been established to monitor fetal outcomes of pregnant women with HIV exposed to dolutegravir. Healthcare professionals are encouraged to register any woman who is on dolutegravir during pregnancy with the Antiretroviral Pregnancy Registry (1-800-258-4263). The CDC recommends that HIV-positive mothers in the United States not breast feed their infants to avoid the risk of HIV transmission.8 It is not known whether dolutegravir is excreted in breast milk in lactating women. Due to the risk of HIV transmission and the unknown effect on the infant if the mother is taking dolutegravir, mothers should be instructed to avoid breastfeeding.2 ■ Adverse reactions Dolutegravir is a well-tolerated ARV. The most common adverse reactions seen in any trial for patients receiving dolutegravir were insomnia and headache, with an incidence of 2% to 3%. Other documented adverse reactions occurring in less than 2% of treatment-naive or treatmentexperienced patients included diarrhea, abdominal pain, nausea, vomiting, fatigue, pruritus, and increased serum lipase levels.2,4-7 ■ Drug interactions Dofetilide is the main drug-drug interaction to keep in mind with dolutegravir. Coadministration of dofetilide with dolutegravir is contraindicated due to possible increases in dofetilide concentrations and the risk of serious and/or lifethreatening events, such as ventricular dysrhythmias and QT interval prolongation.2
12 The Nurse Practitioner • Vol. 39, No. 6
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.tnpj.com
Drug News Concentrations of dolutegravir are decreased in the presence of another ARV drug, etravirine. These two drugs should not be coadministered unless the patient is also on either atazanavir/ ritonavir, darunavir/ritonavir, or lopinavir/ritonavir, as these drugs mitigate that interaction.2 Dolutegravir concentrations are also decreased in the presence of rifampin, efavirenz, fosamprenavir/ ritonavir, and tipranavir/ritonavir. The dose of dolutegravir should be adjusted when it is coadministered with these agents.2 Due to insufficient pharmacokinetic data to make dosing recommendations, it is currently recommended to avoid coadministering dolutegravir with the following medications: nevirapine, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, and St. John’s wort. These recommendations may change as more clinical pharmacokinetic studies are performed with dolutegravir.2 Medications containing cations (for example, magnesium, aluminum, iron, or calcium) can decrease the levels of dolutegravir. Therefore, if the patient is also taking cation-containing antacids, laxatives, sucralfate, oral iron, calcium supplements, or buffered medications, dolutegravir should be taken 2 hours before or 6 hours after these medications.2 (See Patient counseling points.) Dolutegravir can also increase concentrations of metformin. It is recommended to closely monitor patients when starting or stopping these medications and to adjust the dose of metformin as necessary.2 ■ Pharmacokinetics The extent of dolutegravir absorption increases with food while the rate of absorption is decreased. It can be taken with or without food. Peak plasma concentrations of www.tnpj.com
Patient counseling points2 • Tivicay should always be used with other medications that treat HIV • Do not take Tivicay if you take dofetilide, as this combination may be life-threatening • Before taking Tivicay, tell your healthcare provider if you: – have or had liver problems, including hepatitis B or C infection – are pregnant or plan to become pregnant – are breastfeeding or plan to breast-feed. Do not breast-feed if you are infected with HIV. • Tell your healthcare provider about other medications you take, including prescription and over-the-counter drugs, vitamins, or herbal supplements • Tivicay can be taken with or without food • The most common adverse reactions of Tivicay include trouble sleeping and headache
dolutegravir occur 2 to 3 hours after oral administration. When the drug is given once daily, the steady state of dolutegravir is achieved within 5 days.2 Dolutegravir is primarily bound (greater than or equal to 98.9%) to human plasma proteins. It is mostly metabolized by glucuronidation (via UGT1A1), with some contribution from CYP3A. The drug is mainly excreted unchanged in the feces (53%), and other inactive metabolites are excreted in the urine. Renal elimination of unchanged drug is minimal (less than 1%); therefore, dolutegravir dosing adjustments in renal impairment are not needed.2 ■ Clinical pearls • Dolutegravir provides an effective, well-tolerated addition to the integrase inhibitor class of ARV medications. • Dolutegravir is pregnancy category B and should only be used in pregnant women if benefits outweigh the risks. • The most common adverse reactions seen with dolutegravir in clinical trials were insomnia and headache, occurring in only 2% to 3% of patients. • The dosing of dolutegravir depends on the patient’s HIV treatment history and concomitant medications.
REFERENCES 1. STRIBILD [package insert]. Foster City, CA: Gilead Sciences; 2013. 2. TIVICAY [package insert]. Research Triangle Park, NC: GlaxoSmithKline (ViiV Healthcare); 2013. 3. Messiaen P, Wensing AM, Fun A, Nijhuis M, Brusselaers N, Vandekerckhove L. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One. 2013;8(1):e52562. 4. Cahn P, Pozniak AL, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviralexperienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700-708. 5. Raffi F, Rachlis A, Stellbrink HJ, et al. Once-daily dolutegravir versus raltegravir in antiretroviralnaive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013;381(9868):735-743. 6. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807-1818. 7. Nichols G, Mills A, Grossberg R, et al. Antiviral activity of dolutegravir in subjects with failure on an integrase inhibitor-based regimen: week 24 phase 3 results from VIKING-3. Journal of the International AIDS Society. 2012;15(suppl 4):18112. 8. The Centers for Disease Control and Prevention. http://www.cdc.gov/breastfeeding/disease/ index.htm.
Danielle N. Rhyne is a pharmacy resident at the University of Colorado, Aurora, Colo. Emily S. Byrd is a doctorate of pharmacy candidate at Wingate University, Wingate, N.C. Olga M. Klibanov is an associate professor of pharmacy at Wingate University, Wingate, N.C.
The authors have disclosed that they have no financial relationships related to this article.
DOI-10.1097/01.NPR.0000444657.88872.7f
The Nurse Practitioner • June 2014 15
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
