etravirine
etravirine
Pharmacologic class: Nonnucleoside reverse transcriptase inhibitor (NNRTI)
Therapeutic class: Antiretroviral
Pregnancy risk category B
Action
Blocks human immunodeficiency virus (HIV) reverse transcriptase, an enzyme necessary for HIV replication. Blockade leads to reduced viral load and increased CD4+ cell count, which in turn help prevent other infections when drug is given with other antiretrovirals.
Availability
Tablets: 25 mg, 100 mg, 200 mg
Indications and dosages
➣ HIV-1 infection in antiretroviral treatment-experienced patients age 6 and older who have evidence of viral replication and HIV-1 strains resistant to an NNRTI and other antiretrovirals, given in combination with other antiretrovirals
Adults and children ages 6 to younger than 18 weighing 30 kg (66 lb) or more: 200 mg P.O. b.i.d.
Children ages 6 to younger than 18 weighing 25 kg (55 lb) to less than 30 kg: 150 mg P.O. b.i.d.
Children ages 6 to younger than 18 weighing 20 kg (44 lb) to less than 25 kg: 125 mg P.O. b.i.d.
Children ages 6 to younger than 18 weighing 16 kg (35 lb) to less than 20 kg: 100 mg P.O. b.i.d.
Children's dosages shouldn't exceed the recommended adult dosage.
Contraindications
None
Precautions
Use cautiously in:
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 6 (safety and efficacy not established).
Administration
• Administer after a meal.
See Don't give with tipranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, protease inhibitors administered without ritonavir, other NNRTIs, or St. John's wort.
Adverse reactions
CNS: paresthesia, somnolence, seizure, hypoesthesia, amnesia, hypersomnia, tremor, disorientation, insomnia, anxiety, sleep disorder, abnormal dreams, confusional state, nervousness, nightmares, fatigue, peripheral neuropathy, headache, hemorrhagic stroke
CV: syncope, angina pectoris, hypertension, myocardial infarction, atrial fibrillation
EENT: blurred vision, vertigo
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, gastroesophageal reflux disease, flatulence, gastritis, abdominal distention, retching, hematemesis, stomatitis, pancreatitis, anorexia, dry mouth
GU: gynecomastia, renal failure
Hematologic: anemia, hemolytic anemia
Hepatic: cytolytic hepatitis, hepatic steatosis, hepatitis, hepatomegaly
Metabolic: diabetes mellitus, dyslipidemia, body fat redistribution or accumulation
Respiratory: exertional dyspnea, bronchospasm
Skin: rash, hyperhidrosis, prurigo, dry skin, lipohypertrophy, lipodystrophy,
Stevens-Johnson syndrome, erythema multiforme
Other: sluggishness, night sweats, facial edema, immune reconstitution syndrome, hypersensitivity reaction, angioneurotic edema
Interactions
Drug-drug. Amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), lovastatin, mexiletine, propafenone, quinidine, simvastatin: decreased blood levels of these drugs Atazanavir/ritonavir: significant decrease in atazanavir blood level with loss of atazanavir therapeutic effect
Atorvastatin: possible increase in effects of both drugs
Carbamazepine, dexamethasone (systemic), efavirenz, nevirapine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, ritonavir, tipranavir/ritonavir: significant decrease in etravirine blood level and loss of therapeutic effect
Clarithromycin: decreased clarithromycin blood level
Diazepam, fluvastatin, voriconazole, warfarin: increased blood levels of these drugs
Fluconazole, lopinavir/ritonavir, posaconazole: increased etravirine blood level
Immunosuppressants (cyclosporine, sirolimus, tacrolimus): possible change in blood levels of these drugs
Itraconazole, ketoconazole: decreased blood levels of these drugs, increased etravirine blood level
Methadone: possible change in methadone effects
Protease inhibitors (amprenavir, atazanavir, indinavir, nelfinavir) given without low-dose ritonavir: significant change in blood levels of these drugs
Saquinavir/ritonavir: reduced etravirine blood level
Sildenafil: possible decrease in sildenafil effect
Drug-diagnostic tests. ALP, amylase, AST, cholesterol, creatinine, glucose, lipase, low-density lipoproteins, triglycerides: increased levels
Hemoglobin, neutrophils, platelets: decreased levels
Drug-food. Any food: increased etravirine levels
Drug-herbs. St. John's wort: significant decrease in etravirine blood level and loss of therapeutic effect
Patient monitoring
See Monitor patient closely for rash; discontinue therapy if severe rash develops.
• Be aware that immune reconstitution syndrome may occur in patients receiving combination antiretroviral therapy. During initial phase of therapy, patient whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, and tuberculosis), which may necessitate further evaluation and treatment.
• Monitor International Normalized Ratio when giving drug concomitantly with warfarin.
• Watch for new-onset diabetes mellitus, exacerbation of preexisting diabetes, and hyperglycemia.
Patient teaching
• Tell patient to take drug after a meal exactly as prescribed.
• Instruct patient unable to swallow tablets whole to disperse tablets in glass of water, stir dispersion well, drink it immediately, then rinse glass with water several times and completely swallow each rinse to ensure that entire dose is consumed.
• Inform patient that drug doesn't cure HIV infection or reduce risk of passing HIV to others through sexual contact, needle sharing, or blood exposure.
• Advise patient that drug may interact with many other drugs and herbs (especially St. John's wort). Tell patient to discuss use of other drugs and herbs with prescriber.
See Advise patient to immediately report rash or new infections.
• Inform patient that drug may lead to body fat redistribution or accumulation and that the cause and long-term effects of these conditions are unknown.
• Advise female patient to notify prescriber if she is pregnant or intends to become pregnant.
• Because of potential HIV transmission and adverse reactions in breastfeeding infants, instruct women receiving this drug not to breastfeed.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.
etravirine
(e-tra-veer-een) etravirine,Intelence
(trade name)Classification
Therapeutic: antiretroviralsPharmacologic: non nucleoside reverse transcriptase inhibitors
Indications
Action
Therapeutic effects
Pharmacokinetics
Time/action profile (blood levels)
| ROUTE | ONSET | PEAK | DURATION |
|---|---|---|---|
| PO | unknown | 2.5–4 hr | 12 hr |
Contraindications/Precautions
Adverse Reactions/Side Effects
Central nervous system
- seizures (life-threatening)
- anxiety
- confusion
- fatigue
- headache
- insomnia
- sleep disorders
Ear, Eye, Nose, Throat
- blurred vision
- vertigo
Cardiovascular
- myocardial infarction (life-threatening)
- angina pectoris
- atrial fibrillation
- hypertension
Gastrointestinal
- hepatic failure (life-threatening)
- nausea (most frequent)
- abdominal pain
- anorexia
- dry mouth
- hepatitis
- stomatitis
- vomiting
Genitourinary
- renal failure
Endocrinologic
- gynecomastia
- hyperglycemia
- hyperlipidemia
Hematologic
- anemia
- hemolytic anemia
Dermatologic
- erythema multiforme (life-threatening)
- stevens-johnson syndrome (life-threatening)
- toxic epidermal necrolysis (life-threatening)
- rash (most frequent)
Metabolic
- fat redistribution
Neurologic
- peripheral neuropathy
Musculoskeletal
- hemarthrosis
Miscellaneous
- drug rash with eosinophilia and systemic symptoms (dress) (life-threatening)
- immune reconstitution syndrome
Interactions
Drug-Drug interaction
Etravirine is a substrate of the CYP3A4, CYP2C9, and CYP2C19 enzyme systems; other medications that induce or inhibit these systems may be expected to alter the response to etravirine. Etravirine is an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19. The effects of medications that are substrates of these enzyme systems may be altered by concurrent use.Concurrent use with other NNRTIs including efavirenz, nevirapine, rilpivirine, and delavirdine may lead to ↓ effectiveness and should be avoided.Concurrent use with protease inhibitors (PIs), including nelfinavir and indinavir, may lead to altered plasma levels and should be untertaken with concurrent low dose ritonavir.Concurrent use with higher dose ritonavir, combination tipranavir/ritonavir, fosamprenavir/ritonavir, and atazanavir/ritonavir alter levels and effectiveness of etravirine and should be avoided.Concurrent use with lopinavir/ritonavir may ↓ levels.Concurrent use of the combination saquinavir/ritonavir should be undertake cautiously.↓ blood levels and effectiveness of antiarrhythmics including amiodarone, disopyramide, flecainide, lidocaine, mexiletine, quinidine, propafenone, and quinidine ; blood level monitoring recommended.Blood levels and effects may be ↓ by anticonvulsants including carbamazepine, phenobarbital, and phenytoin.Concurrent use with voriconazole may ↑ levels of both drugs; ↓ levels of itraconazole and ketoconazole (dose adjustments may be necessary).Concurrent use with fluconazole may ↑ levels.May alter levels and response to clarithromycin ; other agents should be considered.Rifampin and rifapentine ↓ blood levels and effectiveness and should be avoided; rifabutin should only be used without a protease inhibitor/ritonavir combination.May ↑ blood levels and sedation from diazepam ; monitor for effects.Levels and effectiveness may be ↓ by dexamethasone ; use cautiously and consider alternatives.May alter blood levels and effects of fluvastatin, lovastatin, and simvastatin (dose adjustments may be necessary.May alter blood levels and effects of cyclosporine, sirolimus, and tacrolimus ; careful monitoring required.May ↓ the antiplatelet effects of clopidogrel.May ↓ buprenorphine levels.May ↓ levels of artemether/lumefantrine and telaprevir St. John's wort may ↓ blood levels and effectiveness; avoid concurrent use.Route/Dosage
Availability
Nursing implications
Nursing assessment
- Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
- Assess patient for rash (mild to moderate rash usually occurs in the 2nd wk of therapy and resolves within 1–2 wk of continued therapy). If rash is severe (extensive erythematous or maculopapular rash with moist desquamation or angioedema) or accompanied by systemic symptoms (serum sickness-like reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis), therapy must be discontinued immediately.
- Lab Test Considerations: Monitor viral load and CD4 cell count regularly during therapy.
- Monitor liver function tests periodically during therapy. May cause ↑ serum AST, ALT concentrations.
- May cause ↑ pancreatic amylase and lipase.
- May cause ↑ in total cholesterol, low density lipoprotein, serum triglyceride, and glucose levels.
- May cause ↑ serum creatinine.
- May cause ↓ neutrophils, ↓ platelet count, anemia and hemolytic anemia.
Potential Nursing Diagnoses
Risk for infection (Indications)Noncompliance (Patient/Family Teaching)
Implementation
- Oral: Administer tablets twice daily following a meal; type of food does not matter. Swallow tablet whole; do not break, crush, or chew. If patient has difficulty swallowing, may disperse tablet in 5 mL (1 tsp) of water, or at least enough liquid to cover the medication; stir well until water looks milky. Add more water or orange juice or milk (do not place tablets in orange juice or milk without first adding water). Avoid grapefruit juice, warm, or carbonated beverages. Once dispersed, patient should stir well and drink immediately; rinse glass with water and drink several times to ensure entire dose is consumed.
Patient/Family Teaching
- Emphasize the importance of taking etravirine as directed, at the same time each day. It must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses following a meal if remembered within 6 hr of the time it is usually taken, then return to regular schedule. If more than 6 hr from time dose is usually taken, omit dose and resume dosing schedule; do not double doses.
- Instruct patient that etravirine should not be shared with others.
- Inform patient that etravirine does not cure AIDS or prevent associated or opportunistic infections. Etravirine does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of etravirine are unknown at this time.
- May cause dizziness, impaired concentration, or drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
- Instruct patient to notify health care professional immediately if rash, signs of hypersensitivity (fever, generally ill feeling, extreme tiredness, muscle or joint aches, blisters, oral lesions, eye inflammation, facial swelling), signs and symptoms of liver problems (yellowing of skin or whites of eyes, dark or tea colored urine, pale-colored stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on right side below ribs), or signs of Immune Reconstitution Syndrome (signs and symptoms of an infection) occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
- Inform patient that changes in body fat (increased fat in upper back and neck, breast, and around back, chest, and stomach area; loss of fat from legs, arms, and face) may occur.
- Advise patients taking oral contraceptives to use a nonhormonal method of birth control during etravirine therapy and to notify health care professional if they become pregnant or plan to breast feed while taking etravirine.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
Evaluation/Desired Outcomes
- Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
- Decrease in viral load and increase in CD4 cell counts.