Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Vitekta: 85 mg [DSC], 150 mg [DSC] [contains fd&c blue #2 aluminum lake]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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%
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
Use: Off Label
HIV-1 treatment in antiretroviral-naive patientsyes
Based on the Department of Health and Human Services (HHS) Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, elvitegravir in combination with cobicistat, tenofovir, and emtricitabine is a recommended initial treatment regimen for antiretroviral-naive HIV patients with a pre-ART CrCl>70 mL/minute.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Note: Vitekta has been discontinued in the US for more than 1 year.
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.
Administration
Oral: Administer once daily with food.
Dietary Considerations
Take with food.
Storage
Store below 30°C (86°F). Dispense only in original container.
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 (High risk with Inducers). Monitor therapy
CarBAMazepine: May decrease the serum concentration of Elvitegravir. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). 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 (High risk with Inducers). 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 (High risk with Inducers). 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 (High risk with Inducers). 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
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Estrogen Derivatives (Contraceptive): Elvitegravir may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider the use of an alternative, non-hormone-based contraceptive, in patients who are being treated with elvitegravir-containing products. 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
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
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
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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
Orlistat: May decrease the serum concentration of Antiretroviral Agents. 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
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
St John's Wort: May decrease the serum concentration of Elvitegravir. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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
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-Barré 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.
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.
Pregnancy
Pregnancy Risk Factor
B
Pregnancy Considerations
Elvitegravir has a high level of transfer across the placenta.
Data collected by the antiretroviral pregnancy registry are insufficient to evaluate teratogenic risk. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth -weight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
The Health and Human Services perinatal HIV guidelines do not recommend an elvitegravir-containing regimen in pregnant females living with HIV due to inadequate serum concentrations observed during pregnancy. Pharmacokinetic data are insufficient to make dosing recommendations during pregnancy. If pregnancy occurs during therapy, consideration should be given to changing to a more effective regimen. If continued, close monitoring, including more frequent therapeutic drug monitoring if available, is recommended. Do not administer within 2 hours of iron or calcium containing preparations, including prenatal vitamins.
In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2019).
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.
