Intelence
(Etravirine)Dosage & Administration
By using PrescriberAI, you agree to the AI Terms of Use.
Intelence Prescribing Information
INTELENCE, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients and pediatric patients 2 years of age and older
Etravirine is an NNRTI of HIV-1. Etravirine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. Etravirine does not inhibit the human DNA polymerases α, β, and γ.
Etravirine exhibited activity against laboratory strains and clinical isolates of wild-type HIV-1 in acutely infected T-cell lines, human peripheral blood mononuclear cells, and human monocytes/macrophages with median EC50values ranging from 0.9 to 5.5 nM (i.e., 0.4 to 2.4 ng/mL). Etravirine demonstrated antiviral activity in cell culture against a broad panel of HIV-1 group M isolates (subtype A, B, C, D, E, F, G) with EC50values ranging from 0.29 to 1.65 nM and EC50values ranging from 11.5 to 21.7 nM against group O primary isolates. Etravirine did not show antagonism when studied in combination with the following antiretroviral drugs—the NNRTIs delavirdine, efavirenz, and nevirapine; the N(t)RTIs abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine; the PIs amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir; the gp41 fusion inhibitor ENF; the integrase strand transfer inhibitor raltegravir and the CCR5 co-receptor antagonist maraviroc.
Etravirine-resistant strains were selected in cell culture originating from wild-type HIV-1 of different origins and subtypes, as well as NNRTI resistant HIV-1. Development of reduced susceptibility to etravirine typically required more than one substitution in reverse transcriptase of which the following were observed most frequently: L100I, E138K, E138G, V179I, Y181C, and M230I.
In the Phase 3 trials TMC125-C206 and TMC125-C216, substitutions that developed most commonly in subjects with virologic failure at Week 48 to the INTELENCE-containing regimen were V179F, V179I, and Y181C which usually emerged in a background of multiple other NNRTI resistance-associated substitutions. In all the trials conducted with INTELENCE in HIV-1 infected subjects, the following substitutions emerged most commonly: L100I, E138G, V179F, V179I, Y181C and H221Y. Other NNRTI-resistance-associated substitutions which emerged on etravirine treatment in less than 10% of the virologic failure isolates included K101E/H/P, K103N/R, V106I/M, V108I, Y181I, Y188L, V189I, G190S/C, N348I and R356K. The emergence of NNRTI substitutions on etravirine treatment contributed to decreased susceptibility to etravirine with a median fold-change in etravirine susceptibility of 40-fold from reference and a median fold-change of 6-fold from baseline.
Cross-resistance among NNRTIs has been observed. Cross-resistance to delavirdine, efavirenz, and/or nevirapine is expected after virologic failure with an etravirine-containing regimen. Virologic failure on a rilpivirine-containing regimen with development of rilpivirine resistance is likely to result in cross-resistance to etravirine (see
Etravirine showed antiviral activity against 55 of 65 HIV-1 strains (85%) with single amino acid substitutions at RT positions associated with NNRTI resistance, including the most commonly found K103N. The single amino acid substitutions associated with an etravirine reduction in susceptibility greater than 3-fold were K101A, K101P, K101Q, E138G, E138Q, Y181C, Y181I, Y181T, Y181V, and M230L, and of these, the greatest reductions were Y181I (13-fold change in EC50value) and Y181V (17-fold change in EC50value). Mutant strains containing a single NNRTI resistance-associated substitution (K101P, K101Q, E138Q, or M230L) had cross-resistance between etravirine and efavirenz. The majority (39 of 61; 64%) of the NNRTI mutant viruses with 2 or 3 amino acid substitutions associated with NNRTI resistance had decreased susceptibility to etravirine (fold-change greater than 3). The highest levels of resistance to etravirine were observed for HIV-1 harboring a combination of substitutions V179F + Y181C (187 fold-change), V179F + Y181I (123 fold-change), or V179F + Y181C + F227C (888 fold-change).
Etravirine retained a fold-change less than or equal to 3 against 60% of 6171 NNRTI-resistant clinical isolates. In the same panel, the proportion of clinical isolates resistant to delavirdine, efavirenz and/or nevirapine (defined as a fold-change above their respective biological cutoff values in the assay) was 79%, 87%, and 95%, respectively. In TMC125-C206 and TMC125-C216, 34% of the baseline isolates had decreased susceptibility to etravirine (fold-change greater than 3) and 60%, 69%, and 78% of all baseline isolates were resistant to delavirdine, efavirenz, and nevirapine, respectively. Of subjects who received etravirine and were virologic failures in TMC125-C206 and TMC125-C216, 90%, 84%, and 96% of viral isolates obtained at the time of treatment failure were resistant to delavirdine, efavirenz, and nevirapine, respectively.
There are currently no clinical data available on the use of etravirine in subjects who experienced virologic failure on a rilpivirine-containing regimen. However, in the rilpivirine adult clinical development program, there was evidence of phenotypic cross-resistance between rilpivirine and etravirine. In the pooled analyses of the Phase 3 clinical trials for rilpivirine, 38 rilpivirine virologic failure subjects had evidence of HIV-1 strains with genotypic and phenotypic resistance to rilpivirine. Of these subjects, 89% (34 subjects) of virologic failure isolates were cross-resistant to etravirine based on phenotype data. Consequently, it can be inferred that cross-resistance to etravirine is likely after virologic failure and development of rilpivirine resistance. Refer to the prescribing information for EDURANT (rilpivirine) for further information.
In TMC125-C206 and TMC125-C216, the presence at baseline of the substitutions L100I, E138A, I167V, V179D, V179F, Y181I, Y181V, or G190S was associated with a decreased virologic response to etravirine. Additional substitutions associated with a decreased virologic response to etravirine when in the presence of 3 or more additional 2008 IAS-USA defined NNRTI substitutions include A98G, K101H, K103R, V106I, V179T, and Y181C. The presence of K103N, which was the most prevalent NNRTI substitution in TMC125-C206 and TMC125-C216 at baseline, did not affect the response in the INTELENCE arm. Overall, response rates to etravirine decreased as the number of baseline NNRTI substitutions increased (shown as the proportion of subjects achieving viral load less than 50 plasma HIV RNA copies/mL at Week 48) (Table 10).
| ENF: enfuvirtide | ||
# IAS-USA-Defined NNRTI substitutions | Etravirine N=561 | |
Re-used/not used ENF | de novo ENF | |
All ranges | 61% (254/418) | 76% (109/143) |
0 | 68% (52/76) | 95% (20/21) |
1 | 67% (72/107) | 77% (24/31) |
2 | 64% (75/118) | 86% (38/44) |
3 | 55% (36/65) | 62% (16/26) |
≥ 4 | 37% (19/52) | 52% (11/21) |
Placebo N=592 | ||
All ranges | 34% (147/435) | 59% (93/157) |
Response rates assessed by baseline etravirine phenotype are shown in Table 11. These baseline phenotype groups are based on the select subject populations in TMC125-C206 and TMC125-C216 and are not meant to represent definitive clinical susceptibility breakpoints for INTELENCE. The data are provided to give clinicians information on the likelihood of virologic success based on pre-treatment susceptibility to etravirine in treatment-experienced patients.
| ENF: enfuvirtide | |||
Fold Change | Etravirine N=559 | ||
Re-used/not used ENF | de novo ENF | Clinical response range | |
All ranges | 61% (253/416) | 76% (109/143) | Overall Response |
0–3 | 69% (188/274) | 83% (75/90) | Higher than Overall Response |
> 3–13 | 50% (39/78) | 66% (25/38) | Lower than Overall Response |
> 13 | 41% (26/64) | 60% (9/15) | Lower than Overall Response |
Placebo N=583 | |||
All ranges | 34% (145/429) | 60% (92/154) | |
The proportion of virologic responders (viral load less than 50 HIV-1 RNA copies/mL) by the phenotypic susceptibility score (PSS) of the background therapy, including ENF, is shown in Table 12.
| PSSThe phenotypic susceptibility score (PSS) was defined as the total number of active antiretroviral drugs in the background therapy to which a subject's baseline viral isolate showed sensitivity in phenotypic resistance tests. Each drug in the background therapy was scored as a '1' or '0' based on whether the viral isolate was considered susceptible or resistant to that drug, respectively. In the calculation of the PSS, darunavir was counted as a sensitive antiretroviral if the FC was less than or equal to 10; ENF was counted as a sensitive antiretroviral if it had not been used previously. INTELENCE was not included in this calculation. | INTELENCE + BR N=559 | Placebo + BR N=586 |
|---|---|---|
| 0 | 43% (40/93) | 5% (5/95) |
| 1 | 61% (125/206) | 28% (64/226) |
| 2 | 77% (114/149) | 59% (97/165) |
| ≥ 3 | 75% (83/111) | 72% (72/100) |
The clinical efficacy of INTELENCE is derived from the analyses of 48-week data from 2 ongoing, randomized, double-blinded, placebo-controlled, Phase 3 trials, TMC125-C206 and TMC125-C216 (DUET-1 and DUET-2) in subjects with 1 or more NNRTI resistance-associated substitutions. These trials are identical in design and the results below are pooled data from the two trials.
TMC125-C206 and TMC125-C216 are Phase 3 studies designed to evaluate the safety and antiretroviral activity of INTELENCE in combination with a background regimen (BR) as compared to placebo in combination with a BR. Eligible subjects were treatment-experienced HIV-1-infected subjects with plasma HIV-1 RNA greater than 5000 copies/mL while on an antiretroviral regimen for at least 8 weeks. In addition, subjects had 1 or more NNRTI resistance-associated substitutions at screening or from prior genotypic analysis, and 3 or more of the following primary PI substitutions at screening: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, V82A/F/L/S/T, I84V, N88S, or L90M. Randomization was stratified by the intended use of ENF in the BR, previous use of darunavir/ritonavir, and screening viral load. Virologic response was defined as HIV-1 RNA less than 50 copies/mL at Week 48.
All study subjects received darunavir/ritonavir as part of their BR, and at least 2 other investigator-selected antiretroviral drugs (N[t]RTIs with or without ENF). Of INTELENCE-treated subjects, 25.5% used ENF for the first time (
In the pooled analysis for TMC125-C206 and TMC125-C216, demographics and baseline characteristics were balanced between the INTELENCE arm and the placebo arm (Table 13). Table 13 displays selected demographic and baseline disease characteristics of the subjects in the INTELENCE and placebo arms.
| INTELENCE + BR N=599 | Placebo + BR N=604 | |
|---|---|---|
| RASs = Resistance-Associated Substitutions, BR=background regimen, FC = fold change in EC50 | ||
Demographic characteristics | ||
| Median age, years (range) | 46 (18–77) | 45 (18–72) |
| Sex | ||
| Male | 90.0% | 88.6% |
| Female | 10.0% | 11.4% |
| Race | ||
| White | 70.1% | 69.8% |
| Black | 13.2% | 13.0% |
| Hispanic | 11.3% | 12.2% |
| Asian | 1.3% | 0.6% |
| Other | 4.1% | 4.5% |
Baseline disease characteristics | ||
| Median baseline plasma HIV-1 RNA (range), log10copies/mL | 4.8 (2.7–6.8) | 4.8 (2.2–6.5) |
| Percentage of subjects with baseline viral load: | ||
| < 30,000 copies/mL | 27.5% | 28.8% |
| ≥ 30,000 copies/mL and < 100,000 copies/mL | 34.4% | 35.3% |
| ≥ 100,000 copies/mL | 38.1% | 35.9% |
| Median baseline CD4+ cell count (range), cells/mm3 | 99 (1–789) | 109 (0–912) |
| Percentage of subjects with baseline CD4+ cell count: | ||
| < 50 cells/mm3 | 35.6% | 34.7% |
| ≥ 50 cells/mm3and < 200 cells/mm3 | 34.8% | 34.5% |
| ≥ 200 cells/mm3 | 29.6% | 30.8% |
| Median (range) number of primary PI substitutionsIAS-USA primary PI substitutions [August/September 2007]: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54L/M, L76V, V82A/F/L/S/T, I84V, N88S, L90M | 4 (0–7) | 4 (0–8) |
| Percentage of subjects with previous use of NNRTIs: | ||
| 0 | 8.2% | 7.9% |
| 1 | 46.9% | 46.7% |
| > 1 | 44.9% | 45.4% |
| Percentage of subjects with previous use of the following NNRTIs: | ||
| Efavirenz | 70.3% | 72.5% |
| Nevirapine | 57.1% | 58.6% |
| Delavirdine | 13.7% | 12.6% |
| Median (range) number of NNRTI RASsTibotec NNRTI RASs [June 2008]: A98G, V90I, L100I, K101E/H/P/Q, K103H/N/S/T, V106A/M/I, V108I, E138A/G/K/Q, V179D/E/F/G/I/T, Y181C/I/V, Y188C/H/L, V189I, G190A/C/E/Q/S, H221Y, P255H, F227C/L, M230I/L, P236L, K238N/T, Y318F | 2 (0–8) | 2 (0–7) |
| Median fold change of the virus for the following NNRTIs: | ||
| Delavirdine | 27.3 | 26.1 |
| Efavirenz | 63.9 | 45.4 |
| Etravirine | 1.6 | 1.5 |
| Nevirapine | 74.3 | 74.0 |
| Percentage of subjects with previous use of a fusion inhibitor | 39.6% | 42.2% |
| Percentage of subjects with a Phenotypic Sensitivity Score (PSS) for the background therapyThe PSS was calculated for the background therapy (as determined on Day 7). Percentages are based on the number of subjects with available phenotype data. For fusion inhibitors (enfuvirtide), subjects were considered resistant if the drug was used in previous therapy up to baseline. INTELENCE is not included in this calculation.of: | ||
| 0 | 17.0% | 16.2% |
| 1 | 36.5% | 38.7% |
| 2 | 26.9% | 27.8% |
| ≥ 3 | 19.7% | 17.3% |
Efficacy at Week 48 for subjects in the INTELENCE and placebo arms for the pooled TMC125-C206 and TMC125-C216 study populations are shown in Table 14.
| INTELENCE + BR N=599 | Placebo + BR N=604 | |
|---|---|---|
| BR=background regimen | ||
| Virologic responders at Week 48 Viral Load < 50 HIV-1 RNA copies/mL | 359 (60%) | 232 (38%) |
| Virologic failures at Week 48 Viral Load ≥ 50 HIV-1 RNA copies/mL | 123 (21%) | 201 (33%) |
| Death | 11 (2%) | 19 (3%) |
| Discontinuations before Week 48: | ||
| due to virologic failures | 58 (10%) | 110 (18%) |
| due to adverse events | 31 (5%) | 14 (2%) |
| due to other reasons | 17 (3%) | 28 (5%) |
At Week 48, 70.8% of INTELENCE-treated subjects achieved HIV-1 RNA less than 400 copies/mL as compared to 46.4% of placebo-treated subjects. The mean decrease in plasma HIV-1 RNA from baseline to Week 48 was -2.23 log10copies/mL for INTELENCE-treated subjects and -1.46 log10copies/mL for placebo-treated subjects. The mean CD4+ cell count increase from baseline for INTELENCE-treated subjects was 96 cells/mm3and 68 cells/mm3for placebo-treated subjects.
Of the study population who either re-used or did not use ENF, 57.4% of INTELENCE-treated subjects and 31.7% of placebo-treated subjects achieved HIV-1 RNA less than 50 copies/mL. Of the study population using ENF
Treatment-emergent CDC category C events occurred in 4% of INTELENCE-treated subjects and 8.4% of placebo-treated subjects.
Study TMC125-C227 was a randomized, exploratory, active-controlled, open-label, Phase 2b trial. Eligible subjects were treatment-experienced, PI-naïve HIV-1-infected subjects with genotypic evidence of NNRTI resistance at screening or from prior genotypic analysis. The virologic response was evaluated in 116 subjects who were randomized to INTELENCE (59 subjects) or an investigator-selected PI (57 subjects), each given with 2 investigator-selected N(t)RTIs. INTELENCE-treated subjects had lower antiviral responses associated with reduced susceptibility to the N(t)RTIs and to INTELENCE as compared to the control PI-treated subjects.
The efficacy of INTELENCE for treatment-experienced pediatric subjects is based on two Phase 2 trials, TMC125-C213 and TMC125-C234/IMPAACT P1090.
TMC125-C213, a single-arm, Phase 2 trial evaluating the pharmacokinetics, safety, tolerability, and efficacy of INTELENCE enrolled 101 antiretroviral treatment-experienced HIV-1 infected pediatric subjects 6 years to less than 18 years of age and weighing at least 16 kg. Subjects eligible for this trial were on an antiretroviral regimen with confirmed plasma HIV-1 RNA of at least 500 copies/mL and viral susceptibility to INTELENCE at screening.
The median baseline plasma HIV-1 RNA was 3.9 log10copies/mL, and the median baseline CD4+ cell count was 385 × 106cells/mm3.
At Week 24, 52% of subjects had HIV-1 RNA less than 50 copies per mL. The proportion of subjects with HIV-1 RNA less than 400 copies/mL was 67%. The mean CD4+ cell count increase from baseline was 112 × 106cells/mm3.
TMC125-C234/IMPAACT P1090 is a Phase 1/2 trial evaluating the pharmacokinetics, safety, tolerability, and efficacy of INTELENCE in 20 antiretroviral treatment-experienced HIV-1 infected pediatric subjects 2 years to less than 6 years of age. The study enrolled subjects who had virologic failure on an antiretroviral treatment regimen after at least 8 weeks of treatment, or who had interrupted treatment for at least 4 weeks. Enrolled subjects had a history of virologic failure while on an antiretroviral regimen, with a confirmed HIV-1 RNA plasma viral load greater than 1,000 copies/mL and with no evidence of phenotypic resistance to etravirine at screening.
The median baseline plasma HIV-1 RNA was 4.4 log10copies/mL, the median baseline CD4+ cell count was 817.5 × 106cells/mm3, and the median baseline CD4+ percentage was 28%.
Virologic response, defined as achieving plasma viral load less than 400 HIV-1 RNA copies/mL, was evaluated.
Study treatment included etravirine plus an optimized background regimen of antiretroviral drugs. In addition to etravirine, all 20 subjects received a ritonavir-boosted protease inhibitor in combination with 1 or 2 NRTIs (n=14) and/or in combination with an integrase inhibitor (n=7).
At the time of the Week 24 analysis, seventeen subjects had completed at least 24 weeks of treatment or discontinued earlier. At Week 24, the proportion of subjects with less than 400 HIV-1 RNA copies/mL was 88% (15/17), and the proportion of subjects with less than 50 HIV-1 RNA copies/mL was 50% (7/14), for those with available data. The median change in plasma HIV-1 RNA from baseline to Week 24 was -2.14 log10copies/mL. The median CD4+ cell count increase and the median CD4+ percentage increase from baseline was 298 × 106cells/mm3and 5%, respectively.
- Adult patients: 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. (,
2.1 Recommended Dosage in Adult PatientsThe recommended oral dosage of INTELENCE for adult patients is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. The type of food does not affect the exposure to INTELENCE
[see Clinical Pharmacology (12.3)].,2.2 Recommended Dosage During PregnancyThe recommended oral dosage of INTELENCE for pregnant individuals is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal
[see Use in Specific Populations (8.1)].)2.4 Method of AdministrationInstruct patients to swallow the INTELENCE tablet(s) whole with liquid such as water. Patients who are unable to swallow the INTELENCE tablet(s) whole may disperse the tablet(s) in water. Instruct the patient to do the following:
- place the tablet(s) in 5 mL (1 teaspoon) of water, or at least enough liquid to cover the medication,
- stir well until the water looks milky,
- add approximately 15 mL (1 tablespoon) of liquid. Water may be used but other liquids, such as orange juice or milk, may improve taste. Patients should not place the tablets in orange juice or milk without first adding water. The use of warm (temperature greater than 104°F [greater than 40°C]) or carbonated beverages should be avoided.
- drink the mixture immediately,
- rinse the glass several times with orange juice, milk or water and completely swallow the rinse each time to make sure the patient takes the entire dose.
- Pregnant patients: 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. ()
2.2 Recommended Dosage During PregnancyThe recommended oral dosage of INTELENCE for pregnant individuals is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal
[see Use in Specific Populations (8.1)]. - Pediatric patients (2 years to less than 18 years of age and weighing at least 10 kg): dosage of INTELENCE is based on body weight and should not exceed the recommended adult dose. INTELENCE tablets should be taken following a meal. ()
2.3 Recommended Dosage in Pediatric Patients (2 Years to Less Than 18 Years of Age)The recommended dosage of INTELENCE for pediatric patients 2 years to less than 18 years of age and weighing at least 10 kg is based on body weight (see Table 1) not exceeding the recommended adult dosage. INTELENCE should be taken orally, following a meal. The type of food does not affect the exposure to INTELENCE
[see Clinical Pharmacology (12.3)].Table 1: Recommended Dosage of INTELENCE for Pediatric Patients 2 Years to Less Than 18 Years of Age Body Weight
kilograms (kg)Dose greater than or equal to 10 kg to less than 20 kg 100 mg twice daily greater than or equal to 20 kg to less than 25 kg 125 mg twice daily greater than or equal to 25 kg to less than 30 kg 150 mg twice daily greater than or equal to 30 kg 200 mg twice daily
- 25 mg white to off-white, oval, scored tablets debossed with "TMC" on one side.
- 100 mg white to off-white oval tablets debossed with "TMC125" on one side and "100" on the other side.
- 200 mg white to off-white, biconvex, oblong tablets debossed with "T200" on one side.
- Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission. ()
8.2 LactationRisk SummaryThe Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.
Based on limited data, etravirine has been shown to be present in human breast milk. There are no data on the effects of etravirine on the breastfed infant, or the effects of etravirine on milk production.
Because of the potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants) and (3) adverse reactions in breastfed infants similar to those seen in adults, instruct mothers not to breastfeed if they are receiving INTELENCE.
None.
- Severe, potentially life threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction, toxic epidermal necrolysis and erythema multiforme. Immediately discontinue treatment if severe hypersensitivity, severe rash or rash with systemic symptoms or liver transaminase elevations develops and monitor clinical status, including liver transaminases closely. ()
5.1 Severe Skin and Hypersensitivity ReactionsSevere, potentially life-threatening and fatal skin reactions have been reported. In clinical trials, these include cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme. Hypersensitivity reactions including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have also been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. In Phase 3 clinical trials, Grade 3 and 4 rashes were reported in 1.3% of subjects receiving INTELENCE compared to 0.2% of placebo subjects. A total of 2.2% of HIV-1-infected subjects receiving INTELENCE discontinued from Phase 3 trials due to rash
[see Adverse Reactions (6.1)]. Rash occurred most commonly during the first 6 weeks of therapy. The incidence of rash was higher in females[see Adverse Reactions (6.1)]. Stevens-Johnson syndrome was reported in 1.1% (2/177) of pediatric patients less than 18 years of age receiving INTELENCE in combination with other HIV-1 antiretroviral agents in an observational study.Discontinue INTELENCE immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema). Clinical status including liver transaminases should be monitored and appropriate therapy initiated. Delay in stopping INTELENCE treatment after the onset of severe rash may result in a life-threatening reaction.
- Monitor for immune reconstitution syndrome and fat redistribution. (,
5.3 Immune Reconstitution SyndromeImmune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including INTELENCE. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as
Mycobacterium aviuminfection, cytomegalovirus,Pneumocystis jirovecipneumonia (PCP) or tuberculosis), which may necessitate further evaluation and treatment.Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) 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.
)5.4 Fat RedistributionRedistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.