Emtricitabine / Rilpivirine Hydrochloride / Tenofovir Disoproxil Fumarate

Pronunciation: EM-trye-SYE-ta-been/RIL-pi-VIR-een HYE-droe-KLOR-ide/ten-OF-oh-vir DYE-soe-PROX-il FUE-ma-rate
Class: Antiretroviral combination

Trade Names

Complera
- Tablets, oral emtricitabine 200 mg/rilpivirine 25 mg/tenofovir disoproxil fumarate 300 mg

Pharmacology

Emtricitabine

Inhibits activity of HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5′-triphosphate and by being incorporated into nascent viral DNA, resulting in chain termination.

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Rilpivirine

Inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase.

Tenofovir

Inhibits the activity of HIV-1 reverse transcriptase by competing with deoxyadenosine 5′-triphosphate and by DNA chain termination, after incorporation into DNA.

Indications and Usage

Treatment of HIV-1 infection in antiretroviral treatment–naive adults.

Contraindications

Coadministration with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, systemic dexamethasone (more than a single dose), and/or St. John's wort ( Hypericum perforatum ).

Dosage and Administration

Adults

PO 1 tablet once daily.

Renal Function Impairment
Adults

PO Do not administer to patients with moderate or severe renal impairment, ESRD (CrCl below 50 mL/min), or who are on dialysis.

General Advice

  • Administer with a meal. Protein shakes do not constitute a meal.
  • If a dose is missed within 12 h of the time it is usually taken, advise patient to take the dose as soon as possible and then take the next dose at the regularly scheduled time. If a dose is missed by more than 12 h, the missed dose should not be taken; the usual dosing schedule should be resumed.

Storage/Stability

Store between 59° and 86°F. Dispense only in the original container.

Drug Interactions

No drug interaction studies have been conducted with the fixed-dose combination emtricitabine/rilpivirine/tenofovir. The following drug interactions are for the individual components.

Antacids (eg, aluminum or magnesium hydroxide, calcium carbonate)

Rilpivirine plasma concentrations may be decreased. Use with caution. Antacids should be administered at least 2 h before or at least 4 h after rilpivirine.

Anticonvulsants (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin), glucocorticoids systemic (eg, dexamethasone), proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), rifamycins (eg, rifabutin, rifampin, rifapentine), St. John's wort

Rilpivirine plasma concentrations may be decreased because of CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. Coadministration is contraindicated.

Azole antifungal agents (eg, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole)

Rilpivirine plasma concentrations may be increased. No rilpivirine dose adjustment is needed. Ketoconazole plasma concentrations may be decreased. Monitor for breakthrough fungal infection.

Didanosine

Plasma concentrations of didanosine may be increased by tenofovir. Pharmacologic and toxic effects of didanosine may be increased. Consider a reduction in the dose of didanosine.

H 2 -receptor antagonists (eg, cimetidine, famotidine, nizatidine, ranitidine)

The increase in gastric pH may cause a decrease in rilpivirine plasma concentrations. Use with caution. H 2 -receptor antagonists should be given at least 12 h before or at least 4 h after rilpivirine.

Macrolide antibiotics (eg, clarithromycin, erythromycin)

Rilpivirine plasma concentrations may be increased. When possible, alternative therapy (eg, azithromycin) should be considered.

Methadone

Both rilpivirine and methadone plasma concentrations may be decreased. No dosage adjustments are required. However, clinical monitoring is recommended because methadone maintenance therapy may need to be adjusted in some patients.

Protease inhibitors (eg, atazanavir)

Tenofovir may decrease plasma concentrations and pharmacologic effects of protease inhibitors, and protease inhibitors may increase tenofovir plasma concentrations and risk of toxicity. Closely monitor patients for signs of decreased efficacy to protease inhibitors and increased adverse effects caused by tenofovir.

QT prolonging drugs (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol], arsenic trioxide, chlorpromazine, cisapride, dolasetron, droperidol, gatifloxacin, halofantrine, levomethadyl, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, sparfloxacin, thioridazine, ziprasidone)

Information is limited. An additive effect of rilpivirine with other drugs that prolong the QT interval cannot be excluded. Use rilpivirine with caution when administering with a drug with a known risk of torsades de pointes.

Adverse Reactions

Incidences of the following adverse reactions were reported with combined use of rilpivirine and emtricitabine/tenofovir. Postmarketing reactions were reported with use of emtricitabine or tenofovir.

CNS

Headache, insomnia (2%); abnormal dreams, depressive disorders (eg, depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation), dizziness (1%); asthenia (postmarketing).

Dermatologic

Rash (1%).

GI

Nausea (1%); abdominal pain, pancreatitis (postmarketing).

Genitourinary

Acute renal failure, acute tubular necrosis, Fanconi syndrome, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, polyuria, proteinuria, proximal renal tubulopathy, renal failure, renal insufficiency (postmarketing).

Hepatic

Hepatic steatosis, hepatitis, increased liver enzymes (postmarketing).

Hypersensitivity

Allergic reaction, including angioedema (postmarketing).

Lab Tests

Increased ALT (16%); increased AST, increased total cholesterol (13%); increased LDL (11%); increased creatinine, increased total bilirubin (5%); increased triglycerides (1%); increased amylase, increased creatinine (postmarketing).

Metabolic

Lactic acidosis, hypokalemia and/or hypophosphatemia (these may occur as a consequence of proximal renal tubulopathy) (postmarketing).

Musculoskeletal

Muscular weakness, myopathy, osteomalacia (manifested as bone pain that may contribute to fractures), rhabdomyolysis (these may occur as a consequence of proximal renal tubulopathy) (postmarketing).

Respiratory

Dyspnea (postmarketing).

Precautions

Warnings

Lactic acidosis/severe hepatomegaly with steatosis

Has been reported, including fatal cases, with use of nucleoside analogues, including tenofovir alone and in combination with other antiretroviral agents.

HIV and Hepatitis B coinfection

Not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy have not been established in patients coinfected with HBV and HIV-1. Severe, acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who discontinue therapy and are coinfected with HIV-1 and HBV. If appropriate, initiation of anti-HBV therapy may be warranted.


Monitor

Monitor patient for signs of lactic acidosis and hepatotoxicity. For at least several months, closely monitor hepatic function with clinical and laboratory follow-up in patients who discontinue therapy and are coinfected with HIV and HBV. Consider bone mineral density (BMD) monitoring for HIV-infected patients who have a history of pathologic bone fracture or who are at risk for osteopenia or bone loss. It is recommended that CrCl be calculated in all patients prior to initiating therapy and as clinically appropriate during therapy. Routinely monitor calculated CrCl and serum phosphorus in patients at risk for renal impairment.


Pregnancy

Category B .

Lactation

Undetermined. Advise HIV-infected women not to breast-feed infants.

Children

Safety and efficacy not established.

Elderly

Use with caution because of greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Renal Function

Do not administer to patients with moderate or severe renal impairment or ESRD (CrCl less than 50 mL/min) or to patients requiring dialysis.

Bone effects

Decreases in BMD may occur. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of tenofovir.

Cardiac effects

Subtherapeutic doses of rilpivirine have been shown to prolong the QTc interval of the ECG.

Fat redistribution

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, may occur.

Immune reconstitution syndrome

Has been reported in patients treated with combination antiretroviral therapy, including components of emtricitabine/rilpivirine/tenofovir therapy. Initially, patients may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection), necessitating additional evaluation and treatment.

Psychiatric effects

Depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, and/or suicidal ideation have been reported with rilpivirine.

Renal effects

Renal impairment, including acute renal failure and Fanconi syndrome, has been reported with the use of tenofovir.

Overdosage

Symptoms

None well documented.

Patient Information

  • Advise patient to review the patient information leaflet before starting therapy and with each refill.
  • Advise patients to remain under the care of a health care provider when using emtricitabine/rilpivirine/tenofovir.
  • Inform patients that this product is not a cure for HIV infection. Advise patients to stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses. Tell patients that sustained decreases in plasma HIV RNA have been associated with a reduced risk of progression to AIDS and death.
  • Advise patients to continue to practice safer sex and to use latex or polyurethane condoms to lower the chance of sexual contact with any body fluid, such as semen, vaginal secretions, or blood. Advise patients to never reuse or share needles.
  • Advise patients about the importance of taking emtricitabine/rilpivirine/tenofovir on a regular dosing schedule with a meal and to avoid missing doses. A protein drink does not constitute a meal. Instruct patients that if a dose is missed within 12 h of the time it is usually taken, to take it with a meal as soon as possible and then to take the next dose at the regularly scheduled time. If a dose is missed by more than 12 h, advise patients not to take the missed dose, and to wait and take the next dose as scheduled. Caution patients not to double the next dose to catch up.
  • Advise patients who develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity (including nausea, vomiting, unusual or unexpected stomach discomfort, and weakness) to suspend treatment.
  • Advise patients with HIV to be tested for HBV before initiating therapy. Severe acute exacerbation of hepatitis B have been reported in patients who are coinfected with HBV and HIV and have discontinued emtricitabine or tenofovir. Advise patients not to discontinue therapy without first informing their health care provider.
  • Inform patients that renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported with the use of tenofovir. Avoid therapy with concurrent or recent use of a nephrotoxic agent.
  • Advise patients to report to their health care provider the use of any other prescription or nonprescription medication or herbal products, including St. John's wort.
  • Inform patients that depressive disorder (eg, depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt and/or suicidal ideation) has been reported. If they experience depressive symptoms, advise patients to seek immediate medical attention.
  • Advise patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss to consider BMD monitoring.
  • Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy, and that the cause and long-term effects of this condition are not known.
  • Inform patients that emtricitabine/rilpivirine/tenofovir should not be coadministered with efavirenz/emtricitabine/tenofovir, emtricitabine/tenofovir, emtricitabine, tenofovir or rilpivirine, or with drugs containing lamivudine or adefovir.
  • Inform patients that in some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. Advise patients to inform their health care provider immediately of any symptom of infection.
  • Advise women to notify their health care provider if they are pregnant, planning to become pregnant, or breast-feeding. Advise HIV-infected women not to breast-feed.

Copyright © 2009 Wolters Kluwer Health.

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