If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with VITEKTA consists of general supportive measures including monitoring of vital signs, as well as observation of the clinical status of the patient.
Limited clinical experience is available at doses higher than the therapeutic dose of elvitegravir. The effects of higher doses are not known. As elvitegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis.
There are no contraindications to VITEKTA. Due to the need to use VITEKTA with a protease inhibitor coadministered with ritonavir, prescribers should consult the complete prescribing information of the coadministered protease inhibitor and ritonavir for a description of contraindications.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety assessment of VITEKTA is primarily based on data from a controlled clinical trial, Study 145, in which 712 HIV-1 infected, antiretroviral treatment-experienced adults received VITEKTA (N=354) or raltegravir (N=358), each administered with a background regimen consisting of a fully active protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) for at least 96 weeks.
The proportion of subjects who discontinued study treatment due to adverse events, regardless of severity, was 3% in the VITEKTA group and 4% in the raltegravir group. The most common adverse reaction (all Grades, incidence greater than or equal to 5%) in subjects receiving VITEKTA in Study 145 was diarrhea. See also Table 2 for the frequency of adverse reactions occurring in at least 2% of subjects in any treatment group in Study 145.
Table 2 : Selected Adverse Reactions (All Grades)
Reported in ≥ 2% of HIV-1 Infected Treatment-Experienced Adults in Either
Treatment Group in Study 145 (Week 96 Analysis)a
| VITEKTA N=354 |
Raltegravir N=358 |
|
| Diarrhea | 7% | 5% |
| Nausea | 4% | 3% |
| Headache | 3% | 3% |
| a Frequencies of adverse reactions are based on all adverse events attributed to study drugs. |
The following adverse reactions occurred in < 2% of subjects receiving VITEKTA combined with a protease inhibitor and ritonavir. These reactions have been included because of their seriousness, increased frequency on VITEKTA compared with raltegravir, or investigator's assessment of potential causal relationship.
Gastrointestinal Disorders: abdominal pain, dyspepsia, vomiting
General Disorders and Administration Site Conditions: fatigue
Psychiatric Disorders: depression, insomnia, suicidal ideation and suicide attempt ( < 1%, most in subjects with a pre-existing history of depression or psychiatric illness)
Skin and Subcutaneous Tissue Disorders: rash
Laboratory AbnormalitiesThe frequency of laboratory abnormalities (Grades 3–4), occurring in at least 2% of subjects in either treatment group in Study 145, is presented in Table 3.
Table 3 : Laboratory Abnormalities (Grades 3–4)
Reported in ≥ 2% of HIV-1 Infected Treatment-Experienced Adults in Either
Treatment Group in Study 145 (Week 96 Analysis)
| Laboratory Parameter Abnormality | VITEKTA N=354 |
Raltegravir N=358 |
| Total Bilirubin ( > 2.5 x ULN) | 6% | 9% |
| Hematuria ( > 75 RBC/HPF) | 6% | 7% |
| Serum Amylasea ( > 2.0 x ULN) | 6% | 6% |
| Creatine Kinase ( ≥ 10.0 x ULN) | 6% | 4% |
| Total Cholesterol ( > 300 mg/dL) | 5% | 5% |
| Total Triglycerides ( > 750 mg/dL) | 5% | 4% |
| Hyperglycemia ( > 250 mg/dL) | 5% | 3% |
| Urine Glucose (4+) | 4% | 3% |
| GGT ( > 5.0 x ULN) | 3% | 7% |
| 3 Neutrophils ( < 750/mm ) | 3% | 3% |
| ALT ( > 5.0 x ULN) | 2% | 5% |
| AST ( > 5.0 x ULN) | 2% | 6% |
| a For subjects with serum amylase > 1.5 x upper limit of normal, lipase test was also performed. The frequency of increased lipase (Grades 3–4) occurring in VITEKTA (N=66) and raltegravir (N=58) treatment groups was 14% and 7%, respectively. |
VITEKTA in combination with an HIV protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) is indicated for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults.
Limitations of UseThe effect of multiple doses of elvitegravir 125 mg (1.5 times the lowest recommended dosage) and 250 mg (1.7 times the maximum recommended dosage) (coadministered with 100 mg ritonavir) on QT interval was evaluated in a randomized, placebo-and active-controlled (moxifloxacin 400 mg) parallel group thorough QT study in 126 healthy subjects. No clinically meaningful changes in QTc interval were observed with either 125 mg dose or the 250 mg dose. The dose of 250 mg elvitegravir (with 100 mg ritonavir) is expected to cover the high exposure clinical scenario.
Following oral administration of VITEKTA and ritonavir with food, in HIV-1 infected subjects, peak elvitegravir plasma concentrations were observed approximately 4 hours post-dose. The steady-state mean elvitegravir pharmacokinetic parameters are presented in Table 5. Elvitegravir plasma exposures increased in a less than dose proportional manner, likely due to solubility-limited absorption.
Table 5 : Pharmacokinetic Parameters of Elvitegravir
Following Oral Administration of VITEKTA in HIV-1 Infected Adults
| Parameter Mean ± SD | Elvitegravir 85 mg | Elvitegravir 150 mg |
| Cmax (mcg/mL) | 1.2 ± 0.36 | 1.5 ± 0.37 |
| AUCtau (mcg•hr/mL) | 18 ± 7.1 | 18 ± 6.5 |
| Ctrough (mcg/mL) | 0.42 ± 0.24 | 0.35 ± 0.20 |
| Inhibitory Quotienta | ~ 5 | ~ 9 |
| SD = Standard Deviation a ratio of Ctrough: protein binding-adjusted EC95 for wild-type HIV-1 virus |
VITEKTA must be taken with food.
DistributionElvitegravir is 98–99% bound to human plasma proteins and the binding is independent of drug concentration over the range of 1 ng/mL to 1.6 μg/mL. The mean plasma-toblood drug concentration ratio is 1.37.
Metabolism and EliminationElvitegravir undergoes primarily oxidative metabolism via CYP3A, and is secondarily glucuronidated via UGT1A1/3 enzymes. Following oral administration of [14C]elvitegravir/ritonavir, elvitegravir was the predominant species in plasma, representing ~94% of the circulating radioactivity. Aromatic and aliphatic hydroxylation or glucuronidation metabolites were present in very low levels, displayed considerably lower anti-HIV activity and did not contribute to the overall antiviral activity of elvitegravir.
Following oral administration of [14C]elvitegravir/ritonavir, 94.8% of the dose was recovered in feces, consistent with the hepatobiliary excretion of elvitegravir; 6.7% of the administered dose was recovered in urine as metabolites. The median terminal plasma half-life of elvitegravir following administration of VITEKTA and ritonavir was approximately 8.7 hours.
Pregnancy Category B
There are no adequate and well-controlled studies of VITEKTA in pregnant women. Because animal reproduction studies are not always predictive of human response, VITEKTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Antiretroviral Pregnancy RegistryTo monitor fetal outcomes of pregnant women exposed to VITEKTA, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients by calling 1-800-258-4263.
Animal DataElvitegravir studies in animals have shown no evidence of teratogenicity or an effect on reproductive function. In offspring from rat and rabbit dams treated with VITEKTA during pregnancy, there were no toxicologically significant effects on developmental endpoints. The exposures (AUC) at the embryo-fetal No Observed Adverse Effects Levels (NOAELs) in rats and rabbits were respectively 23 and 0.2 times higher than the exposure in humans at the recommended daily dose of 150 mg.
VITEKTA tablets are available in bottles containing 30 tablets with a child-resistant closure as follows:
85 mg tablets are green, pentagon-shaped, film-coated, debossed with “GSI” on one side and “85” on the other side: NDC 61958-1301-1
150 mg tablets are green, triangle-shaped, film-coated, debossed with “GSI” on one side and “150” on the other side: NDC 61958-1302-1
Store at room temperature below 30 °C (86 °F).
Dispense only in original container.
Do not use if seal over bottle opening is broken or missing.
Manufactured and distributed by: Gilead Sciences, Inc. Foster City, CA 94404. Revised: July 2015
Included as part of the PRECAUTIONS section.
PRECAUTIONS Risk Of Adverse Reactions Or Loss Of Virologic Response Due To Drug InteractionsThe concomitant use of VITEKTA and other drugs may result in known or potentially significant drug interactions, some of which may lead to :
See Table 4 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during VITEKTA therapy; review concomitant medications during VITEKTA therapy; and monitor for the adverse reactions associated with the concomitant drugs.
Use With Other Antiretroviral AgentsUse of VITEKTA in combination with the fixed dose combination STRIBILD is not recommended, because elvitegravir is a component of STRIBILD.
VITEKTA is indicated for use in combination with a protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s). VITEKTA in combination with a protease inhibitor and cobicistat is not recommended because dosing recommendations for such combinations have not been established and may result in suboptimal plasma concentrations of VITEKTA and/or the protease inhibitor, leading to loss of therapeutic effect and development of resistance.
Immune Reconstitution SyndromeImmune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Patient Counseling InformationAdvise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
A statement to patients and healthcare providers is included on the product's bottle label: ALERT: Find out about medicines that should NOT be taken with VITEKTA. A Patient Package Insert for VITEKTA is available for patient information.
Information For PatientsAdvise patients of the following:
Long-term carcinogenicity studies of elvitegravir were carried out in mice (104 weeks) and in rats (up to 88 weeks in males and 90 weeks in females). No drug-related increases in tumor incidence were found in mice at doses up to 2000 mg per kg per day alone or in combination with 25 mg per kg per day ritonavir at exposures 3-and 14-fold, respectively, the human systemic exposure at the recommended daily dose of 150 mg. No drug-related increases in tumor incidence were found in rats at doses up to 2000 mg per kg per day at exposures 12-to 27-fold, respectively, in male and female, the human systemic exposure.
MutagenesisElvitegravir was not genotoxic in the reverse mutation bacterial test (Ames test) and the rat micronucleus assay. In an in vitro chromosomal aberration test, elvitegravir was negative with metabolic activation; however, an equivocal response was observed without activation.
FertilityElvitegravir did not affect fertility in male and female rats at approximately 16-and 30fold higher exposures (AUC), respectively, than in humans at the therapeutic 150 mg daily dose.
Fertility was normal in the offspring of rats exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 18-fold higher than human exposures at the recommended 150 mg daily dose.
Use In Specific Populations PregnancyPregnancy Category B
There are no adequate and well-controlled studies of VITEKTA in pregnant women. Because animal reproduction studies are not always predictive of human response, VITEKTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Antiretroviral Pregnancy RegistryTo monitor fetal outcomes of pregnant women exposed to VITEKTA, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients by calling 1-800-258-4263.
Animal DataElvitegravir studies in animals have shown no evidence of teratogenicity or an effect on reproductive function. In offspring from rat and rabbit dams treated with VITEKTA during pregnancy, there were no toxicologically significant effects on developmental endpoints. The exposures (AUC) at the embryo-fetal No Observed Adverse Effects Levels (NOAELs) in rats and rabbits were respectively 23 and 0.2 times higher than the exposure in humans at the recommended daily dose of 150 mg.
Nursing MothersThe Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants, to avoid risking postnatal transmission of HIV. Studies in rats have demonstrated that elvitegravir is secreted in milk. It is not known whether elvitegravir is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving VITEKTA.
Pediatric UseSafety and efficacy in pediatric patients have not been established.
Adolescents (12 through 17 Years Old)Study 152 was an open-label, multicenter trial of VITEKTA in HIV-1 infected, antiretroviral treatment-experienced adolescent subjects 12 through 17 years of age. The trial included a 10-day pharmacokinetic evaluation phase of VITEKTA followed by an optional extended treatment phase. Dosage regimens were similar to those evaluated in adults, either VITEKTA 150 mg plus darunavir/ritonavir, fosamprenavir/ritonavir, or tipranavir/ritonavir (n=11) or VITEKTA 85 mg plus lopinavir/ritonavir or atazanavir/ritonavir (n=14).
Twenty-five subjects were enrolled and 23 completed the pharmacokinetic phase. Nine subjects with baseline HIV-1 RNA greater than 1,000 copies/mL who completed the 10-day pharmacokinetic evaluation phase enrolled in the optional 48 week treatment phase. All nine completed treatment through 48 weeks; 2/9 subjects (22%) achieved HIV-1 RNA less than 50 copies/mL at Week 48, and 4/9 (44%) achieved HIV-1 RNA less than 400 copies/mL. During the treatment phase of the trial, 8/9 subjects (89%) were found to have undetectable elvitegravir levels during treatment, suggesting that adherence to the regimen was poor and may have contributed to the low response rate in this trial. Although adolescents achieved acceptable VITEKTA plasma levels in the pharmacokinetic phase, the 48-week treatment phase data were insufficient to establish safety and effectiveness in this age group.
Pediatric Patients Less Than 12 Years OldPharmacokinetics, safety and effectiveness of VITEKTA in the treatment of HIV-1 infection in pediatric patients less than 12 years of age have not been evaluated in clinical trials.
Geriatric UseClinical trials of VITEKTA did not include sufficient numbers of subjects aged 65 and older, to determine whether they respond differently from younger subjects. In general, dose selection for elderly patients should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Renal ImpairmentNo clinically relevant differences in elvitegravir pharmacokinetics were observed between subjects with severe renal impairment and healthy subjects. No dose adjustment of VITEKTA is required for patients with renal impairment.
Hepatic ImpairmentNo clinically relevant differences in elvitegravir pharmacokinetics were observed between subjects with moderate hepatic impairment (Child-Pugh Class B) and healthy subjects. No dose adjustment of VITEKTA is required in patients with mild (Child-Pugh Class A) or moderate hepatic impairment. VITEKTA has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Therefore, VITEKTA is not recommended for use in patients with severe hepatic impairment.
VITEKTA must be administered once daily with food in combination with a protease inhibitor coadministered with ritonavir and another antiretroviral drug. The protease inhibitor and ritonavir dosing regimens presented in Table 1 are the recommended regimens for use with VITEKTA. For additional dosing instructions for these protease inhibitors and other concomitant antiretroviral drugs, refer to their respective prescribing information.
Table 1 : Recommended Regimens*
| Dosage of VITEKTA | Dosage of Concomitant Protease Inhibitor | Dosage of Concomitant Ritonavir |
| 85 mg orally once daily | Atazanavir 300 mg orally once daily | 100 mg orally once daily |
| Lopinavir 400 mg orally twice daily | 100 mg orally twice daily | |
| 150 mg orally once daily | Darunavir 600 mg orally twice daily | 100 mg orally twice daily |
| Fosamprenavir 700 mg orally twice daily | 100 mg orally twice daily | |
| Tipranavir 500 mg orally twice daily | 200 mg orally twice daily | |
| *VITEKTA in combination with a protease inhibitor and ritonavir must be coadministered with another antiretroviral drug. |
Treatment history and, when available, resistance testing should guide the use of VITEKTA-containing regimens.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety assessment of VITEKTA is primarily based on data from a controlled clinical trial, Study 145, in which 712 HIV-1 infected, antiretroviral treatment-experienced adults received VITEKTA (N=354) or raltegravir (N=358), each administered with a background regimen consisting of a fully active protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) for at least 96 weeks.
The proportion of subjects who discontinued study treatment due to adverse events, regardless of severity, was 3% in the VITEKTA group and 4% in the raltegravir group. The most common adverse reaction (all Grades, incidence greater than or equal to 5%) in subjects receiving VITEKTA in Study 145 was diarrhea. See also Table 2 for the frequency of adverse reactions occurring in at least 2% of subjects in any treatment group in Study 145.
Table 2 : Selected Adverse Reactions (All Grades)
Reported in ≥ 2% of HIV-1 Infected Treatment-Experienced Adults in Either
Treatment Group in Study 145 (Week 96 Analysis)a
| VITEKTA N=354 |
Raltegravir N=358 |
|
| Diarrhea | 7% | 5% |
| Nausea | 4% | 3% |
| Headache | 3% | 3% |
| a Frequencies of adverse reactions are based on all adverse events attributed to study drugs. |
The following adverse reactions occurred in < 2% of subjects receiving VITEKTA combined with a protease inhibitor and ritonavir. These reactions have been included because of their seriousness, increased frequency on VITEKTA compared with raltegravir, or investigator's assessment of potential causal relationship.
Gastrointestinal Disorders: abdominal pain, dyspepsia, vomiting
General Disorders and Administration Site Conditions: fatigue
Psychiatric Disorders: depression, insomnia, suicidal ideation and suicide attempt ( < 1%, most in subjects with a pre-existing history of depression or psychiatric illness)
Skin and Subcutaneous Tissue Disorders: rash
Laboratory AbnormalitiesThe frequency of laboratory abnormalities (Grades 3–4), occurring in at least 2% of subjects in either treatment group in Study 145, is presented in Table 3.
Table 3 : Laboratory Abnormalities (Grades 3–4)
Reported in ≥ 2% of HIV-1 Infected Treatment-Experienced Adults in Either
Treatment Group in Study 145 (Week 96 Analysis)
| Laboratory Parameter Abnormality | VITEKTA N=354 |
Raltegravir N=358 |
| Total Bilirubin ( > 2.5 x ULN) | 6% | 9% |
| Hematuria ( > 75 RBC/HPF) | 6% | 7% |
| Serum Amylasea ( > 2.0 x ULN) | 6% | 6% |
| Creatine Kinase ( ≥ 10.0 x ULN) | 6% | 4% |
| Total Cholesterol ( > 300 mg/dL) | 5% | 5% |
| Total Triglycerides ( > 750 mg/dL) | 5% | 4% |
| Hyperglycemia ( > 250 mg/dL) | 5% | 3% |
| Urine Glucose (4+) | 4% | 3% |
| GGT ( > 5.0 x ULN) | 3% | 7% |
| 3 Neutrophils ( < 750/mm ) | 3% | 3% |
| ALT ( > 5.0 x ULN) | 2% | 5% |
| AST ( > 5.0 x ULN) | 2% | 6% |
| a For subjects with serum amylase > 1.5 x upper limit of normal, lipase test was also performed. The frequency of increased lipase (Grades 3–4) occurring in VITEKTA (N=66) and raltegravir (N=58) treatment groups was 14% and 7%, respectively. |
See also DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY.
Effect Of Concomitant Drugs On The Pharmacokinetics Of ElvitegravirElvitegravir is metabolized by CYP3A. Drugs that induce CYP3A activity are expected to increase the clearance of elvitegravir, as well as ritonavir. This may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance.
Established And Other Potentially Significant InteractionsTable 4 provides dosing recommendations as a result of potentially clinically significant drug interactions with VITEKTA. These recommendations are based on either drug-drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of therapeutic effect.
For additional drug-drug interactions related to protease inhibitors coadministered with ritonavir, consult the prescribing information of the coadministered protease inhibitor and ritonavir.
The table is not all-inclusive.
Table 4 : Established and Other Potentially
Significanta Drug Interactions: Alteration in Dose or Regimen May Be
Recommended Based on Drug Interaction Studies or Predicted Interaction
| Concomitant Drug Class: Drug Name | Effect on Concentrationb | Clinical Comment |
| Antiretroviral Agents: Protease Inhibitors (PIs) c | ||
| Atazanavir* | ↔ atazanavir ↑ elvitegravir |
There are no data available to make dosing recommendations for coadministration with doses of atazanavir/ritonavir other than 300/100 mg once daily. Please refer to Section 2 for dosage adjustments. |
| Lopinavir/ritonavir* | ↔ lopinavir ↑ elvitegravir |
There are no data available to make dosing recommendations for coadministration with doses of lopinavir/ritonavir other than 400/100 mg twice daily. Please refer to Section 2 for dosage adjustments. |
| Other Protease Inhibitors (with or without ritonavir) | Effect is unknown | There are no data available to make dosing recommendations for coadministration with protease inhibitors other than atazanavir, lopinavir/ritonavir, darunavir, fosamprenavir, and tipranavir. |
| Antiretroviral Agents: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | ||
| Didanosine* | ↔ didanosine ↔ elvitegravir |
As didanosine is administered on an empty stomach, administer didanosine at least 1 hour before or 2 hours after VITEKTA (which is administered with food). |
| Antiretroviral Agents: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) | ||
| Efavirenz | ↓ elvitegravir | Coadministration of VITEKTA with efavirenz is not recommended. |
| Nevirapine | ↓ elvitegravir | Coadministration of VITEKTA with nevirapine is not recommended. |
| Other Agents: | ||
| Acid Reducing Agents: antacids* | ↓ elvitegravir | Separate VITEKTA and antacid administration by at least 2 hours. |
| Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin |
↓ elvitegravir | Coadministration of VITEKTA with phenobarbital, phenytoin, carbamazepine, or oxcarbazepine is not recommended. |
| Antifungals: ketoconazole* | ↑ elvitegravir ↑ ketoconazole |
No dose adjustment of VITEKTA is required when coadministered with ketoconazole. When ketoconazole is used concomitantly with VITEKTA in combination with protease inhibitors/ritonavir; the maximum daily dose of ketoconazole should not exceed 200 mg per day. Consult the prescribing information of coadministered protease inhibitors for any additional dosing recommendation for ketoconazole. |
| Antimycobacterials: rifampin rifapentine rifabutin* |
↓ elvitegravir | Coadministration of VITEKTA with rifampin or rifapentine is not recommended. |
| ↑ rifabutin ↑ 25-Odesacetylrifabutin ↓ elvitegravir |
When rifabutin is used concomitantly with VITEKTA in combination with a protease inhibitor/ritonavir, dose reduction of rifabutin by at least 75% of the usual dose of 300 mg/day (eg, 150 mg every other day or 3 times per week) is recommended. Increased monitoring for rifabutin-associated adverse events is warranted. Consult the prescribing information of coadministered protease inhibitors for any additional dosing recommendation for rifabutin. No dose adjustment of VITEKTA is required when coadministered with the reduced dose of rifabutin. | |
| Systemic Corticosteroids: dexamethasone | ↓ elvitegravir | Alternative corticosteroids should be considered. |
| Endothelin Receptor Antagonists: bosentan | ↑ bosentan ↓ elvitegravir |
Coadministration of bosentan in patients on VITEKTA: In patients who have been receiving VITEKTA for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. Coadministration of VITEKTA in patients on bosentan: Discontinue use of bosentan at least 36 hours prior to initiation of VITEKTA. After at least 10 days following the initiation of VITEKTA, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability. |
| HCV Protease Inhibitors: boceprevir | ↓ boceprevir ↑ or ↓ HIV protease inhibitors |
Coadministration of VITEKTA with boceprevir is not recommended. |
| Herbal Products: St. John’s wort (Hypericum perforatum) | ↓ elvitegravir | Coadministration of VITEKTA with St. John’s wort is not recommended. |
| Hormonal Contraceptives: norgestim ate/ethi n yl estradiol | ↑ norgestimate ↓ ethinyl estradiol ↔ elvitegravir |
Alternative methods of non-hormonal contraception are recommended. |
| Narcotic Analgesics: buprenorphine/ naloxone* | ↑ buprenorphine ↑ norbuprenorphine ↓ naloxone |
No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects. |
| methadone | ↓ methadone | Dosage of methadone may need to be increased when coadministered with VITEKTA |
| * Indicates that a drug-drug interaction trial was
conducted. a This table is not all inclusive. b ↑ = Increase, ↓ = Decrease, ↔ = No change c Protease inhibitors were coadministered with ritonavir. |
||
Based on drug interaction studies conducted with elvitegravir, no clinically significant drug interactions have been either observed or expected when elvitegravir is combined with the following drugs: abacavir, darunavir, emtricitabine, etravirine, fosamprenavir, maraviroc, stavudine, tipranavir, tenofovir disoproxil fumarate, zidovudine; H2-receptor antagonists such as famotidine; proton-pump inhibitors such as omeprazole; and the HMG-CoA reductase inhibitors atorvastatin, pravastatin, and rosuvastatin.
When any of the above drugs are used concomitantly with VITEKTA in combination with a protease inhibitor coadministered with ritonavir, consult the prescribing information of the protease inhibitor for dosing recommendation for these drugs.
