Intelence

• Generic Name: entravirine tablets
• Brand Name: Intelence
• Drug Class: HIV, NNRTIs

Intelence (Entravirine Tablets) side effects drug center

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• Intelence User Reviews

PROFESSIONAL

CONSUMER

SIDE EFFECTS

• Overview
• Consumer Information
• Professional Information

Intelence Side Effects Center

What Is Intelence?

Intelence (etravirine) is an antiviral medication used with other medications to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). This drug is not a cure for HIV or AIDS, and it is usually given after other antiviral drugs have been tried unsuccessfully.

What Are Side Effects of Intelence?

Common side effects of Intelence include:

• nausea,
• rash,
• numbness or tingly feeling in your hands or feet,
• dizziness,
• drowsiness,
• blurred vision,
• upset stomach,
• constipation,
• heartburn,
• dry mouth,
• unusual dreams, or
• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist)

Dosage for Intelence

The recommended adult oral dose of Intelence is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. Pediatric dose is based on body weight.

What Drugs, Substances, or Supplements Interact with Intelence?

Intelence may interact with blood thinners, clopidogrel, darunavir, lopinavir/ritonavir, dexamethasone, diazepam, cyclosporine, cholesterol medications, maraviroc, methadone, sildenafil, sirolimus, tacrolimus, antibiotics, antifungals, or heart rhythm medications. Many other medicines can interact with Intelence, or make it less effective. Tell your doctor all medications and supplements you use.

Intelence During Pregnancy or Breastfeeding

During pregnancy, Intelence should be used only when prescribed. It is unknown if this medication passes into breast milk. Because breast milk can transmit HIV, do not breastfeed.

Additional Information

Our Intelence (etravirine) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Intelence Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Call your doctor at once if you have:

• unexplained muscle pain, tenderness, or weakness;
• fever, unusual tiredness;
• dark colored urine; or
• any type of skin rash, no matter how mild.

Etravirine affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss;
• trouble speaking or swallowing, problems with balance or eye movement, weakness or prickly feeling; or
• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.

Common side effects may include:

• diarrhea;
• numbness or tingly feeling in your hands or feet;
• rash; or
• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Intelence (Entravirine Tablets)

 

Intelence Professional Information

SIDE EFFECTS

The following adverse reactions are described in greater detail in other sections:

• Severe skin and hypersensitivity reactions [see WARNINGS AND PRECAUTIONS].
• Immune reconstitution syndrome [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

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.

Clinical Trials Experience In Adults

The safety assessment is based on all data from 1203 subjects in the Phase 3 placebo-controlled trials, TMC125-C206 and TMC125-C216, conducted in antiretroviral treatment-experienced HIV-1-infected adult subjects, 599 of whom received INTELENCE (200 mg twice daily). In these pooled trials, the median exposure for subjects in the INTELENCE arm and placebo arm was 52.3 and 51.0 weeks, respectively. Discontinuations due to adverse drug reactions (ADRs) were 5.2% in the INTELENCE arm and 2.6% in the placebo arm.

The most frequently reported ADR at least Grade 2 in severity was rash (10.0%). Stevens-Johnson syndrome, drug hypersensitivity reaction and erythema multiforme were reported in less than 0.1% of subjects during clinical development with INTELENCE [see WARNINGS AND PRECAUTIONS]. A total of 2.2% of HIV-1-infected subjects in Phase 3 trials receiving INTELENCE discontinued due to rash. In general, in clinical trials, rash was mild to moderate, occurred primarily in the second week of therapy, and was infrequent after Week 4. Rash generally resolved within 1 to 2 weeks on continued therapy. The incidence of rash was higher in women compared to men in the INTELENCE arm in the Phase 3 trials (rash ≥ Grade 2 was reported in 9/60 [15.0%] women versus 51/539 [9.5%] men; discontinuations due to rash were reported in 3/60 [5.0%] women versus 10/539 [1.9%] men) [see WARNINGS AND PRECAUTIONS]. Patients with a history of NNRTI-related rash did not appear to be at increased risk for the development of INTELENCE-related rash compared to patients without a history of NNRTI-related rash.

Common Adverse Reactions

Clinical ADRs of moderate intensity or greater (greater than or equal to Grade 2) and reported in at least 2% of subjects treated with INTELENCE and occurring at a higher rate compared to placebo (excess of 1%) are presented in Table 2. Laboratory abnormalities considered ADRs are included in Table 3.

Table 2: Adverse Drug Reactions (Grades 2 to 4) in at Least 2% of Adult Subjects (Pooled TMC125-C206 and TMC125-C216 Trials)

Preferred Term	INTELENCE + BR N=599 %	Placebo + BR N=604 %
Rash	10%	3%
Peripheral neuropathy	4%	2%
N=total number of subjects per treatment group; BR=background regimen

Less Common Adverse Reactions

Treatment-emergent ADRs occurring in less than 2% of subjects (599 subjects) receiving INTELENCE and of at least moderate intensity (greater than or equal to Grade 2) are listed below by body system:

Cardiac Disorders: myocardial infarction, angina pectoris, atrial fibrillation

Ear and Labyrinth Disorders: vertigo

Eye Disorders: blurred vision

Gastrointestinal Disorders: gastroesophageal reflux disease, flatulence, gastritis, abdominal distension, pancreatitis, constipation, dry mouth, hematemesis, retching, stomatitis

General Disorders and Administration Site Conditions: sluggishness

Hematologic Disorders: hemolytic anemia

Hepatobiliary Disorders: hepatic failure, hepatomegaly, cytolytic hepatitis, hepatic steatosis, hepatitis

Immune System Disorders: drug hypersensitivity, immune reconstitution syndrome

Metabolism and Nutrition Disorders: diabetes mellitus, anorexia, dyslipidemia

Nervous System Disorders: paresthesia, somnolence, convulsion, hypoesthesia, amnesia, syncope, disturbance in attention, hypersomnia, tremor

Psychiatric Disorders: anxiety, sleep disorders, abnormal dreams, confusional state, disorientation, nervousness, nightmares

Renal and Urinary Disorders: acute renal failure

Reproductive System and Breast Disorders: gynecomastia

Respiratory, Thoracic and Mediastinal Disorders: exertional dyspnea, bronchospasm

Skin and Subcutaneous Tissue Disorders: night sweats, lipohypertrophy, prurigo, hyperhidrosis, dry skin, swelling face

Additional ADRs of at least moderate intensity observed in other trials were acquired lipodystrophy, angioneurotic edema, erythema multiforme and hemorrhagic stroke, each reported in no more than 0.5% of subjects.

Laboratory Abnormalities in Treatment-Experienced Patients

Selected Grade 2 to Grade 4 laboratory abnormalities that represent a worsening from baseline observed in adult subjects treated with INTELENCE are presented in Table 3.

Table 3: Selected Grade 2 to 4 Laboratory Abnormalities Observed in Treatment- Experienced Subjects (Pooled TMC125-C206 and TMC125-C216 Trials)

Laboratory Parameter	DAIDS Toxicity Range	INTELENCE + BR N=599 %	Placebo + BR N=604 %
GENERAL BIOCHEMISTRY
Pancreatic amylase
Grade 2	> 1.5–2 x ULN	7%	8%
Grade 3	> 2–5 x ULN	7%	8%
Grade 4	> 5 x ULN	2%	1%
Lipase
Grade 2	> 1.5–3 x ULN	4%	6%
Grade 3	> 3–5 x ULN	2%	2%
Grade 4	> 5 x ULN	1%	< 1%
Creatinine
Grade 2	> 1.4–1.8 x ULN	6%	5%
Grade 3	> 1.9–3.4 x ULN	2%	1%
Grade 4	> 3.4 x ULN	0%	< 1%
HEMATOLOGY
Decreased hemoglobin
Grade 2	90–99 g/L	2%	3%
Grade 3	70–89 g/L	1%	4%
Grade 4	< 70 g/L	1%	< 1%
White blood cell count
Grade 2	1,500–1,999/mm3	2%	3%
Grade 3	1,000–1,499/mm3	1%	4%
Grade 4	< 1,000/mm3	1%	< 1%
Neutrophils
Grade 2	750–999/mm3	5%	6%
Grade 3	500–749/mm3	4%	4%
Grade 4	< 500/mm3	2%	3%
Platelet count
Grade 2	50,000–99,999/mm3	3%	5%
Grade 3	25,000–49,999/mm3	1%	1%
Grade 4	< 25,000/mm3	< 1%	< 1%
LIPIDS AND GLUCOSE
Total cholesterol
Grade 2	> 6.20–7.77 mmol/L 240–300 mg/dL	20%	17%
Grade 3	> 7.77 mmol/L > 300 mg/dL	8%	5%
Low density lipoprotein
Grade 2	4.13–4.9 mmol/L 160–190 mg/dL	13%	12%
Grade 3	> 4.9 mmol/L > 190 mg/dL	7%	7%
Triglycerides
Grade 2	5.65–8.48 mmol/L 500–750 mg/dL	9%	7%
Grade 3	8.49–13.56 mmol/L 751–1200 mg/dL	6%	4%
Grade 4	> 13.56 mmol/L > 1200 mg/dL	4%	2%
Elevated glucose levels
Grade 2	6.95–13.88 mmol/L 161–250 mg/dL	15%	13%
Grade 3	13.89–27.75 mmol/L 251–500 mg/dL	4%	2%
Grade 4	> 27.75 mmol/L > 500 mg/dL	0%	< 1%
HEPATIC PARAMETERS
Alanine amino transferase
Grade 2	2.6–5 x ULN	6%	5%
Grade 3	5.1–10 x ULN	3%	2%
Grade 4	> 10 x ULN	1%	< 1%
Aspartate amino transferase
Grade 2	2.6–5 x ULN	6%	8%
Grade 3	5.1–10 x ULN	3%	2%
Grade 4	> 10 x ULN	< 1%	< 1%
ULN=Upper Limit of Normal; BR=background regimen

Patients Co-Infected With Hepatitis B and/or Hepatitis C Virus

In Phase 3 trials TMC125-C206 and TMC125-C216, 139 subjects (12.3%) with chronic hepatitis B and/or hepatitis C virus co-infection out of 1129 subjects were permitted to enroll. AST and ALT abnormalities occurred more frequently in hepatitis B and/or hepatitis C virus co-infected subjects for both treatment groups. Grade 2 or higher laboratory abnormalities that represent a worsening from baseline of AST, ALT or total bilirubin occurred in 27.8%, 25.0% and 7.1% respectively, of INTELENCE-treated co-infected subjects as compared to 6.7%, 7.5% and 1.8% of non-co-infected INTELENCE-treated subjects. In general, adverse events reported by INTELENCE-treated subjects with hepatitis B and/or hepatitis C virus coinfection were similar to INTELENCE-treated subjects without hepatitis B and/or hepatitis C virus co-infection.

Clinical Trials Experience In Pediatric Subjects (2 Years To Less Than 18 Years Of Age)

The safety assessment in pediatric subjects is based on two single-arm trials. TMC125-C213 is a Phase 2 trial in which 101 antiretroviral treatment-experienced HIV-1 infected pediatric subjects 6 years to less than 18 years of age received INTELENCE in combination with other antiretroviral agents (Week 24 analysis). TMC125-C234/IMPAACT P1090 is a Phase 1/2 trial in which 20 antiretroviral treatment-experienced HIV-1 infected pediatric subjects 2 years to less than 6 years of age received INTELENCE in combination with other antiretroviral agents (Week 24 analysis) [see Clinical Studies].

In TMC125-C213, the frequency, type and severity of adverse drug reactions in pediatric subjects 6 years to less than 18 years of age were comparable to those observed in adult subjects, except for rash which was observed more frequently in pediatric subjects. The most common adverse drug reactions in at least 2% of pediatric subjects were rash and diarrhea. Rash was reported more frequently in female subjects than in male subjects (rash ≥ Grade 2 was reported in 13/64 [20.3%] females versus 2/37 [5.4%] males; discontinuations due to rash were reported in 4/64 [6.3%] females versus 0/37 [0%] males). Rash (greater than or equal to Grade 2) occurred in 15% of pediatric subjects from 6 years to less than 18 years of age. In the majority of cases, rash was mild to moderate, of macular/papular type, and occurred in the second week of therapy. Rash was self-limiting and generally resolved within 1 week on continued therapy. The safety profile for subjects who completed 48 weeks of treatment was similar to the safety profile for subjects who completed 24 weeks of treatment.

In TMC125-C234/IMPAACT P1090, the frequency, type and severity of adverse drug reactions in pediatric subjects 2 years to less than 6 years of age through Week 24 were comparable to those observed in adults. The most common adverse drug reactions (any grade) of pediatric subjects were rash (50% [10/20]) and diarrhea (25% [5/20]). In this age group, no subjects had Grade 3 or Grade 4 rash and no subjects discontinued prematurely due to rash. One subject discontinued etravirine due to asymptomatic lipase elevation.

Postmarketing Experience

The following events have been identified during postmarketing use of INTELENCE. Because these events are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Severe hypersensitivity reactions including DRESS and cases of hepatic failure have been reported [see WARNINGS AND PRECAUTIONS].

Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis

Skin and Subcutaneous Tissue Disorders: Fatal cases of toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported [see WARNINGS AND PRECAUTIONS].

DRUG INTERACTIONS

Potential For Other Drugs To Affect INTELENCE

Etravirine is a substrate of CYP3A, CYP2C9, and CYP2C19. Therefore, co-administration of INTELENCE with drugs that induce or inhibit CYP3A, CYP2C9, and CYP2C19 may alter the therapeutic effect or adverse reaction profile of INTELENCE (see Table 4) [see CLINICAL PHARMACOLOGY].

Potential For INTELENCE To Affect Other Drugs

Etravirine is an inducer of CYP3A and inhibitor of CYP2C9, CYP2C19 and P-glycoprotein (P-gp). Therefore, coadministration of drugs that are substrates of CYP3A, CYP2C9 and CYP2C19 or are transported by P-gp with INTELENCE may alter the therapeutic effect or adverse reaction profile of the co-administered drug(s) (see Table 4) [see CLINICAL PHARMACOLOGY].

Significant Drug Interactions

Table 4 shows significant drug interactions based on which, alterations in dose or regimen of INTELENCE and/or coadministered drug may be recommended. Drugs that are not recommended for co-administration with INTELENCE are also included in Table 4 [see CLINICAL PHARMACOLOGY].

Table 4: Significant Drug Interactions

Concomitant Drug Class: Drug Name	Effect on Concentration of Etravirine or Concomitant Drug	Clinical Comment
HIV-antiviral agents: integrase strand inhibitors
dolutegravir*	↓ dolutegravir ↔ etravirine	Etravirine significantly reduced plasma concentrations of dolutegravir. Using cross-study comparisons to historical pharmacokinetic data for etravirine, dolutegravir did not appear to affect the pharmacokinetics of etravirine.
dolutegravir/darunavir/ritonavir*	↓ dolutegravir ↔ etravirine	The effect of etravirine on dolutegravir plasma concentrations was mitigated by co-administration of darunavir/ritonavir or lopinavir/ritonavir, and is expected to be mitigated by atazanavir/ritonavir. Dolutegravir should only be used with INTELENCE when co-administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir.
dolutegravir/lopinavir/ritonavir*	↔ dolutegravir ↔ etravirine
HIV-antiviral agents: non-nucleoside reverse transcriptase inhibitors (NNRTIs)
efavirenz* nevirapine*	↓ etravirine	Combining two NNRTIs has not been shown to be beneficial. Concomitant use of INTELENCE with efavirenz or nevirapine may cause a significant decrease in the plasma concentrations of etravirine and loss of therapeutic effect of INTELENCE. Coadministration of INTELENCE and other NNRTIs is not recommended.
delavirdine	↑ etravirine	Combining two NNRTIs has not been shown to be beneficial. INTELENCE and delavirdine should not be coadministered.
rilpivirine	↓ rilpivirine ↔ etravirine	Combining two NNRTIs has not been shown to be beneficial. Coadministration of INTELENCE and rilpivirine is not recommended.
HIV-antiviral agents: protease inhibitors (PIs)
atazanavir* (without ritonavir)	↓ atazanavir	Co-administration of INTELENCE and atazanavir without low-dose ritonavir is not recommended.
atazanavir/ritonavir*	↓ atazanavir ↔ etravirine	Concomitant use of INTELENCE with atazanavir/ritonavir decreased atazanavir C but it is not considered clinically relevant. The mean systemic exposure (AUC) of etravirine after coadministration of INTELENCE with atazanavir/ritonavir in HIV-infected subjects was similar to the mean systemic exposure of etravirine observed in the Phase 3 trials after coadministration of INTELENCE and darunavir/ritonavir (as part of the background regimen). INTELENCE and atazanavir/ritonavir can be coadministered without dose adjustments.
atazanavir/cobicistat	↓ atazanavir ↓ cobicistat	Co-administration of INTELENCE with atazanavir/cobicistat is not recommended because it may result in loss of therapeutic effect and development of resistance to atazanavir. The mean systemic exposure (AUC) of etravirine was reduced when INTELENCE was co-administered with darunavir/ritonavir. Because all subjects in the Phase 3 trials received darunavir/ritonavir as part of the background regimen and etravirine exposures from these trials were determined to be safe and effective, INTELENCE and darunavir/ritonavir can be co-administered without dose adjustments.
darunavir/ritonavir*	↓ etravirine
darunavir/cobicistat	↓ cobicistat darunavir: effect unknown	Co-administration of INTELENCE with darunavir/cobicistat is not recommended because it may result in loss of therapeutic effect and development of resistance to darunavir. Concomitant use of INTELENCE with fosamprenavir without low-dose ritonavir may cause a significant alteration in the plasma concentration of amprenavir. Co-administration of INTELENCE and fosamprenavir without low-dose ritonavir is not recommended.
fosamprenavir (without ritonavir)	↑ amprenavir
fosamprenavir/ritonavir*	↑ amprenavir	Due to a significant increase in the systemic exposure of amprenavir, the appropriate doses of the combination of INTELENCE and fosamprenavir/ritonavir have not been established. Co-administration of INTELENCE and fosamprenavir/ritonavir is not recommended.
indinavir* (without ritonavir)	↓ indinavir	Concomitant use of INTELENCE with indinavir without low-dose ritonavir may cause a significant alteration in the plasma concentration of indinavir. Coadministration of INTELENCE and indinavir without low-dose ritonavir is not recommended.
lopinavir/ritonavir*	↓ etravirine	The mean systemic exposure (AUC) of etravirine was reduced after coadministration of INTELENCE with lopinavir/ritonavir (tablet). Because the reduction in the mean systemic exposures of etravirine in the presence of lopinavir/ritonavir is similar to the reduction in mean systemic exposures of etravirine in the presence of darunavir/ritonavir, INTELENCE and lopinavir/ritonavir can be coadministered without dose adjustments.
nelfinavir (without ritonavir)	↑ nelfinavir	Concomitant use of INTELENCE with nelfinavir without low-dose ritonavir may cause a significant alteration in the plasma concentration of nelfinavir. Coadministration of INTELENCE and nelfinavir without low-dose ritonavir is not recommended.
ritonavir*	↓ etravirine	Concomitant use of INTELENCE with ritonavir 600 mg twice daily may cause a significant decrease in the plasma concentration of etravirine and loss of therapeutic effect of INTELENCE. Coadministration of INTELENCE and ritonavir 600 mg twice daily is not recommended.
saquinavir/ritonavi*	↓ etravirine	The mean systemic exposure (AUC) of etravirine was reduced when INTELENCE was co-administered with saquinavir/ritonavir. Because the reduction in the mean systemic exposures of etravirine in the presence of saquinavir/ritonavir is similar to the reduction in mean systemic exposures of etravirine in the presence of darunavir/ritonavir, INTELENCE and saquinavir/ritonavir can be coadministered without dose adjustments.
tipranavir/ritonavi*	↓ etravirine	Concomitant use of INTELENCE with tipranavir/ritonavir may cause a significant decrease in the plasma concentrations of etravirine and loss of therapeutic effect of INTELENCE. Coadministration of INTELENCE and tipranavir/ritonavir is not recommended.
CCR5 antagonists
maraviroc*	↔ etravirine ↓ maraviroc	When INTELENCE is co-administered with maraviroc in the absence of a potent CYP3A inhibitor (e.g., ritonavir boosted protease inhibitor), the recommended dose of maraviroc is 600 mg twice daily. No dose adjustment of INTELENCE is needed.
maraviroc/darunavir/ritonavir*†	↔ etravirine ↑ maraviroc	When INTELENCE is co-administered with maraviroc in the presence of a potent CYP3A inhibitor (e.g., ritonavir boosted protease inhibitor), the recommended dose of maraviroc is 150 mg twice daily. No dose adjustment of INTELENCE is needed.
Other agents
Antiarrhythmics: digoxin*	↔ etravirine ↑ digoxin	For patients who are initiating a combination of INTELENCE and digoxin, the lowest dose of digoxin should initially be prescribed. For patients on a stable digoxin regimen and initiating INTELENCE, no dose adjustment of either INTELENCE or digoxin is needed. The serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect.
amiodarone bepridil disopyramide flecainide lidocaine (systemic) mexiletine propafenone quinidine	↓ antiarrhythmics	Concentrations of these antiarrhythmics may be decreased when coadministered with INTELENCE. INTELENCE and antiarrhythmics should be co-administered with caution. Drug concentration monitoring is recommended, if available.
Anticoagulant: warfarin	↑ anticoagulants	Warfarin concentrations may be increased when co-administered with INTELENCE. The international normalized ratio (INR) should be monitored when warfarin is combined with INTELENCE.
Anticonvulsants: carbamazepine phenobarbital phenytoin	↓ etravirine	Carbamazepine, phenobarbital and phenytoin are inducers of CYP450 enzymes. INTELENCE should not be used in combination with carbamazepine, phenobarbital, or phenytoin as co-administration may cause significant decreases in etravirine plasma concentrations and loss of therapeutic effect of INTELENCE.
Antifungals: fluconazole*	↑ etravirine ↔ fluconazole	Co-administration of etravirine and fluconazole significantly increased etravirine exposures. The amount of safety data at these increased etravirine exposures is limited, therefore, etravirine and fluconazole should be coadministered with caution. No dose adjustment of INTELENCE or fluconazole is needed.
voriconazole*	↑ voriconazole	Co-administration of etravirine and voriconazole significantly increased etravirine exposures. The amount of safety data at these increased etravirine exposures is limited, therefore, etravirine and voriconazole should be co-administered with caution. No dose adjustment of INTELENCE or voriconazole is needed.
Antifungals: itraconazole ketoconazole posaconazole	↑ etravirine ↓ itraconazole ↓ ketoconazole ↔ posaconazole	Posaconazole, a potent inhibitor of CYP3A4, may increase plasma concentrations of etravirine. Itraconazole and ketoconazole are potent inhibitors as well as substrates of CYP3A4. Concomitant systemic use of itraconazole or ketoconazole and INTELENCE may increase plasma concentrations of etravirine. Simultaneously, plasma concentrations of itraconazole or ketoconazole may be decreased by INTELENCE. Dose adjustments for itraconazole, ketoconazole or posaconazole may be necessary depending on the other coadministered drugs.
Antiinfective: clarithromycin*	↑ etravirine ↓ clarithromycin ↑ 14-OHclarithromycin	Clarithromycin exposure was decreased by INTELENCE; however, concentrations of the active metabolite, 14-hydroxy-clarithromycin, were increased. Because 14-hydroxyclarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered. Alternatives to clarithromycin, such as azithromycin, should be considered for the treatment of MAC.
Antimalarial: artemether/lumefantrine*	↔ etravirine ↓ artemether ↓ dihydroartemisinin ↓ lumefantrine	Caution is warranted when coadministering INTELENCE and artemether/lumefantrine as it is unknown whether the decrease in exposure of artemether or its active metabolite, dihydroartemisinin, could result in decreased antimalarial efficacy. No dose adjustment is needed for INTELENCE.
Antimycobacterials: rifampin rifapentine	↓ etravirine	Rifampin and rifapentine are potent inducers of CYP450 enzymes. INTELENCE should not be used with rifampin or rifapentine as coadministration may cause significant decreases in etravirine plasma concentrations and loss of therapeutic effect of INTELENCE.
Antimycobacterial: rifabutin*	↓ etravirine ↓ rifabutin ↓ 25-Odesacetylrifabutin	If INTELENCE is NOT coadministered with a protease inhibitor/ritonavir, then rifabutin at a dose of 300 mg once daily is recommended. If INTELENCE is co-administered with darunavir/ritonavir, lopinavir/ritonavir or saquinavir/ritonavir, then rifabutin should not be co-administered due to the potential for significant reductions in etravirine exposure.
Benzodiazepine: diazepam	↑ diazepam	Concomitant use of INTELENCE with diazepam may increase plasma concentrations of diazepam. A decrease in diazepam dose may be needed.
Corticosteroid: dexamethasone (systemic)	↓ etravirine	Systemic dexamethasone induces CYP3A and can decrease etravirine plasma concentrations. This may result in loss of therapeutic effect of INTELENCE. Systemic dexamethasone should be used with caution or alternatives should be considered, particularly for long-term use.
Herbal products: St. John's wort (Hypericum perforatum)	↓ etravirine	Concomitant use of INTELENCE with products containing St. John's wort may cause significant decreases in etravirine plasma concentrations and loss of therapeutic effect of INTELENCE. INTELENCE and products containing St. John's wort should not be coadministered.
Hepatitis C virus (HCV) direct-acting antivirals:
daclatasvir	↓ daclatasvir	Co-administration of INTELENCE with daclatasvir may decrease daclatasvir concentrations. Increase the daclatasvir dose to 90 mg once daily.
elbasvir/grazoprevir	↓ elbasvir ↓ grazoprevir	Co-administration of INTELENCE with elbasvir/grazoprevir may decrease elbasvir and grazoprevir concentrations, leading to reduced therapeutic effect of elbasvir/grazoprevir. Co-administration is not recommended.
simeprevir	↓ simeprevir	Co-administration of INTELENCE with simeprevir may decrease simeprevir concentrations. Coadministration is not recommended.
HMG-CoA reductase inhibitors:atorvastatin*	↔ etravirine ↓ atorvastatin ↑ 2-OHatorvastatin	The combination of INTELENCE and atorvastatin can be given without dose adjustments, however, the dose of atorvastatin may need to be altered based on clinical response.
pravastatin rosuvastatin	↔ etravirine ↔ pravastatin ↔ rosuvastatin	No interaction between pravastatin, rosuvastatin and INTELENCE is expected.
lovastatin simvastatin	↓ lovastatin ↓ simvastatin	Lovastatin and simvastatin are CYP3A substrates and co-administration with INTELENCE may result in lower plasma concentrations of the HMGCoA reductase inhibitor.
fluvastatin pitavastatin	↑ fluvastatin ↑ pitavastatin	Fluvastatin and pitavastatin are metabolized by CYP2C9 and coadministration with INTELENCE may result in higher plasma concentrations of the HMG-CoA reductase inhibitor. Dose adjustments for these HMG-CoA reductase inhibitors may be necessary.
Immunosuppressants: cyclosporine sirolimus tacrolimus	↓ immunosuppressant	INTELENCE and systemic immunosuppressants should be coadministered with caution because plasma concentrations of cyclosporine, sirolimus, or tacrolimus may be affected.
Narcotic analgesics/treatment of opioid dependence: buprenorphine buprenorphine/naloxone* methadone*	↔ etravirine ↓ buprenorphine ↔ norbuprenorphine ↔ methadone	INTELENCE and buprenorphine (or buprenorphine/naloxone) can be coadministered without dose adjustments, however, clinical monitoring for withdrawal symptoms is recommended as buprenorphine (or buprenorphine/naloxone) maintenance therapy may need to be adjusted in some patients. INTELENCE and methadone can be co-administered without dose adjustments, however, clinical monitoring for withdrawal symptoms is recommended as methadone maintenance therapy may need to be adjusted in some patients.
Phosphodiesterase type 5 (PDE-5) inhibitors: sildenafil* tadalafil vardenafil	↓ sildenafil ↓ N-desmethylsildenafil	INTELENCE and sildenafil can be coadministered without dose adjustments, however, the dose of sildenafil may need to be altered based on clinical effect.
Platelet aggregation inhibitors: clopidogrel	↓ clopidogrel (active) metabolite	Activation of clopidogrel to its active metabolite may be decreased when clopidogrel is co-administered with INTELENCE. Alternatives to clopidogrel should be considered.
↑= increase; ↓ = decrease; ↔ = no change *The interaction between INTELENCE and the drug was evaluated in a clinical study. All other drug interactions shown are predicted. †The reference for etravirine exposure is the pharmacokinetic parameters of etravirine in the presence of darunavir/ritonavir.

Drugs Without Clinically Significant Interactions With INTELENCE

In addition to the drugs included in Table 4, the interaction between INTELENCE and the following drugs were evaluated in clinical studies and no dose adjustment is needed for either drug [see CLINICAL PHARMACOLOGY]: didanosine, enfuvirtide (ENF), ethinylestradiol/norethindrone, omeprazole, paroxetine, raltegravir, ranitidine, and tenofovir disoproxil fumarate.

Read the entire FDA prescribing information for Intelence (Entravirine Tablets)

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