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Elvitegravir


General


Pronunciation

(el vi TEG ra vir)


Brand Names: U.S.

  • Vitekta

Indications


Use: Labeled Indications

HIV-1 infection: In combination with an HIV protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults


Contraindications


There are no contraindications listed in the manufacturers labeling.


Dosing and Administration


Dosing: Adult

HIV-1 infection in antiretroviral treatment-experienced patients: Oral: Note:Must be administered in combination with a protease inhibitor, ritonavir, and another antiretroviral drug. See individual agents.

Administered with concomitant atazanavir and ritonavir or lopinavir and ritonavir: 85 mg once daily

Administered with concomitant darunavir and ritonavir, fosamprenavir and ritonavir, or tipranavir and ritonavir: 150 mg once daily


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment necessary.


Dosing: Hepatic Impairment

Mild-to-moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe hepatic impairment (Child-Pugh class C): Use is not recommended (has not been studied).


Administration

Oral: Administer once daily with food.


Dietary Considerations

Take with food.


Storage

Store below 30 ‚ °C (86 ‚ °F). Dispense only in original container.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Vitekta: 85 mg, 150 mg [contains fd&c blue #2 aluminum lake]


Drug Interactions

Antacids: May decrease the serum concentration of Elvitegravir. Management: Separate administration of antacids and elvitegravir-containing products by at least 2 hours in order to minimize the risk for an interaction. Consider therapy modification

Atazanavir: May increase the serum concentration of Elvitegravir. Specifically, atazanavir/ritonavir may increase the concentration of elvitegravir. Management: When elvitegravir is combined with atazanavir/ritonavir, the dose of elvitegravir should be reduced to 85 mg once daily and the dose of atazanavir/ritonavir should be 300 mg/100 mg once daily. Avoid the use of atazanavir/cobicistat and elvitegravir. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Elvitegravir. Avoid combination

Contraceptives (Estrogens): Elvitegravir may decrease the serum concentration of Contraceptives (Estrogens). Management: Consider the use of an alternative, non-hormone-based contraceptive, in patients who are being treated with elvitegaravir-containing products. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Darunavir: May increase the serum concentration of Elvitegravir. Management: When elvitegravir is combined with darunavir/ritonavir, the dose of elvitegravir should remain 150 mg once daily and the dose of darunavir/ritonavir should be 600 mg/100 mg twice daily. Avoid the combination of darunavir/cobicistat and elvitegravir. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Dexamethasone (Systemic): May decrease the serum concentration of Elvitegravir. Management: Consider using an alternative corticosteroid. Monitor patients receiving these agents in combination for diminished antiviral response. Consider therapy modification

Efavirenz: May decrease the serum concentration of Elvitegravir. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of Elvitegravir. Avoid combination

Itraconazole: May increase the serum concentration of Elvitegravir. Management: Limit itraconazole to a maximum dose of 200 mg/day in patients who are being treated with the elvitegravir-containing products. Consider therapy modification

Ketoconazole (Systemic): May increase the serum concentration of Elvitegravir. Management: Limit ketoconazole to a maximum dose of 200 mg/day in patients who are being treated with an elvitegravir-containing product. Consider therapy modification

Lopinavir: May increase the serum concentration of Elvitegravir. Specifically, lopinavir/ritonavir may increase the concentration of elvitegravir. Management: When elvitegravir is combined with lopinavir/ritonavir, the dose of elvitegravir should be reduced to 85 mg once daily and the dose of lopinavir/ritonavir should be 400 mg/100 mg twice daily. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nevirapine: May decrease the serum concentration of Elvitegravir. Avoid combination

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Elvitegravir. Management: For elvitegravir plus a ritonavir-boosted protease inhibitor, use of oxcarbazepine is not recommended; for elvitegravir/cobicistat/emtricitabine/tenofovir combination products, consider using an alternative antiepileptic when possible. Avoid combination

PHENobarbital: May decrease the serum concentration of Elvitegravir. Avoid combination

Rifabutin: Elvitegravir may increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may decrease the serum concentration of Elvitegravir. Management: For single-agent elvitegravir, a rifabutin dose reduction of at least 75% is required (ie, reduction to adult dose of 150 mg every other day or three times/week). Use of elvitegravir combination products with rifabutin is not recommended. Avoid combination

RifAMPin: May decrease the serum concentration of Elvitegravir. Avoid combination

Rifapentine: May decrease the serum concentration of Elvitegravir. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

St Johns Wort: May decrease the serum concentration of Elvitegravir. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Voriconazole: May increase the serum concentration of Elvitegravir. Management: Careful consideration of the risk/benefit ratio for voriconazole use is recommended prior to its use in patients treated with elvitegravir-containing products. Consider therapy modification


Monitoring Parameters

CBC with differential, reticulocyte count, CD4 count, HIV RNA plasma levels, hepatic function tests, testing for HBV is recommended prior to the initiation of antiretroviral therapy.


Adverse Reactions


Percentages are reported for antiretroviral treatment experienced adults.

1% to 10%:

Central nervous system: Headache (3%), depression (<2%), fatigue (<2%), insomnia (<2%), suicidal ideation (<2%)

Dermatologic: Skin rash (<2%)

Gastrointestinal: Diarrhea (7%), nausea (4%), abdominal pain (<2%), dyspepsia (<2%), vomiting (<2%)

Immunologic: Immune reconstitution syndrome


Warnings/Precautions


Concerns related to adverse effects:

- Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves ' disease, polymyositis, Guillain-Barre syndrome) later in therapy; further evaluation and treatment may be required.

Disease-related concerns:

- Hepatic impairment: No dosage adjustment is required in mild or moderate (Child-Pugh class A or B) hepatic impairment. Use is not recommended in severe hepatic impairment (Child-Pugh class C); has not been studied in this population.

Concurrent drug therapy issues:

- Appropriate use: Not recommended in combination with a protease inhibitor and cobicistat due to lack of dosing recommendations, potential suboptimal plasma concentrations, loss of therapeutic effect, or development of resistance. Administration of unboosted elvitegravir is not recommended (HHS [adult] 2015).

- Concurrent therapy: Avoid concurrent use with other elvitegravir-containing products.

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events were not observed in animal reproduction studies; data collected by the antiretroviral pregnancy registry is insufficient to evaluate human teratogenic risk. It is not known if elvitegravir crosses the human placenta. The HHS Perinatal HIV Guidelines note that due to a lack of data, elvitegravir cannot be recommended in antiretroviral-naive pregnant women; pharmacokinetic data are insufficient to make dosing recommendations during pregnancy.

Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women. The goal of therapy is to keep the viral load below the limit of detection and prevent perinatal transmission. Therapy must be individualized. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, contraindications for use in pregnancy are not present, and the regimen is well tolerated. For HIV infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s). When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should be considered as soon as possible after diagnosis to reduce the risk of perinatal transmission. If antiretroviral drug-resistance testing is done, treatment may be started prior to obtaining results, then adjusted accordingly. Monitoring during pregnancy is more frequent than in non-pregnant adults. If cART must be interrupted for <24 hours, stop then restart all medications simultaneously in order to decrease the chance of developing resistance. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.

HIV infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (DHHS [perinatal] 2016).


Actions


Pharmacology

Integrase is an HIV-1 encoded enzyme that is required for viral replication. Inhibition of integrase prevents the integration of HIV-1 DNA into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation of the viral infection. Elvitegravir does not inhibit human topoisomerases I or II.


Absorption

AUC increases with food


Metabolism

Hepatic via CYP3A enzymes and also hepatic glucuronidation mediated by UGT1A1/3


Excretion

Feces (~95%); urine (~7%)


Time to Peak

Plasma: ~4 hours


Half-Life Elimination

Terminal: ~9 hours


Protein Binding

99%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience diarrhea. Have patient report immediately to prescriber signs of infection (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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