Complera (emtricitabine, rilpivirine, tenofovir disoproxil fumarate)

Testing Prior To Initiation And During Treatment With Complera

• Prior to or when initiating Complera, test patients for hepatitis B virus infection.
• Prior to initiation of Complera, and during treatment with Complera, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.

Recommended Dosage

• Complera is a three-drug fixed dose combination product containing 200 mg of emtricitabine (FTC), 25 mg of rilpivirine (RPV), and 300 mg of tenofovir disoproxil fumarate (TDF).
• The recommended dosage of Complera in adult and pediatric patients weighing at least 35 kg is one tablet taken orally once daily with food.

Recommended Dosage During Pregnancy

• For pregnant patients who are already on Complera prior to pregnancy and are virologically suppressed (HIV-1 RNA less than 50 copies per mL), one tablet of Complera taken once daily may be continued.
• Lower exposures of rilpivirine, a component of Complera, were observed during pregnancy, therefore viral load should be monitored closely.

Not Recommended In Patients With Moderate Or Severe Renal Impairment

• Complera is not recommended in patients with moderate or severe renal impairment (estimated creatinine clearance below 50 mL per minute).

Recommended Dosage With Rifabutin Coadministration

• If Complera is coadministered with rifabutin, take an additional 25 mg tablet of rilpivirine (Edurant) with Complera once daily with a meal for the duration of the rifabutin coadministration .

Not Recommended With Other Antiretroviral Medications

• Because Complera is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Comprehensive information regarding potential drug-drug interactions with other antiretroviral medications is not provided.
• This section describes clinically relevant drug interactions with Complera. Drug interaction studies were conducted with the components of Complera (FTC, RPV, and TDF as single agents) or with Complera as a combination product.

Drugs Inducing Or Inhibiting CYP3A Enzymes

• Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of RPV.
• Coadministration of RPV and drugs that induce CYP3A may result in decreased plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs.
• Coadministration of RPV and drugs that inhibit CYP3A may result in increased plasma concentrations of RPV.

Drugs Increasing Gastric pH

• Coadministration of RPV with drugs that increase gastric pH may decrease plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs. Use of RPV with proton pump inhibitors is contraindicated and use of RPV with H2-receptor antagonists requires staggered administration.

Drugs Affecting Renal Function

• Because FTC and tenofovir are primarily eliminated by the kidneys through a combination of glomerular filtration and active tubular secretion, coadministration of Complera with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of FTC, tenofovir, and/or other renally eliminated drugs. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs.

QT Prolonging Drugs

• There is limited information available on the potential for a pharmacodynamic interaction between RPV and drugs that prolong the QTc interval of the electrocardiogram.
•  In a study of healthy subjects, 75 mg once daily and 300 mg once daily doses of RPV (3 times and 12 times the dose in Complera) have been shown to prolong the QTc interval of the electrocardiogram. Consider alternatives to Complera when coadministered with a drug with a known risk of Torsade de Pointes.

Significant Drug Interactions

• Important drug interaction information for Complera is summarized in Table 4. The drug interactions described are based on studies conducted with FTC, RPV, or TDF as individual medications or with Complera as a combination product, or are potential drug interactions. See prescribing information for list of contraindicated drugs.

Table 4 : Significanta Drug Interactions

Drugs With No Observed Interactions With Complera

• No clinically significant drug interactions have been observed between FTC and the following medications:
  • famciclovir,
  • ledipasvir/sofosbuvir,
  • sofosbuvir/velpatasvir,
  • sofosbuvir/velpatasvir/voxilaprevir, or
  • TDF.
• No clinically significant drug interactions have been observed between TDF and the following medications:
  • entecavir,
  • methadone,
  • oral contraceptives,
  • ribavirin,
  • sofosbuvir, or
  • tacrolimus in studies conducted in healthy subjects.
• No clinically significant drug interactions have been observed between RPV and the following medications:
  • acetaminophen,
  • atorvastatin,
  • chlorzoxazone,
  • ethinyl estradiol,
  • ledipasvir/sofosbuvir,
  • norethindrone,
  • sildenafil,
  • simeprevir,
  • sofosbuvir,
  • sofosbuvir/velpatasvir,
  • sofosbuvir/velpatasvir/voxilaprevir, or
  • TDF.
• RPV did not have a clinically significant effect on the pharmacokinetics of digoxin or metformin.

• Available data from the APR show no increase in the overall risk of major birth defects with first trimester exposure for emtricitabine (FTC), rilpivirine (RPV), or tenofovir (TDF) compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
• In a clinical trial, total rilpivirine exposures were generally lower during pregnancy compared to the postpartum period.
• The rate of miscarriage for individual drugs is not reported in the APR.
• The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15-20%.
• Based on the experience of HIV-1-infected pregnant individuals who completed a clinical trial through the postpartum period with an RPV-based regimen, no dose adjustments are required for pregnant patients who are already on a stable RPV-containing regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL). Lower exposures of RPV were observed during pregnancy, therefore viral load should be monitored closely.
• The Centers for Disease Control and Prevention recommend that HIV infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.
• Based on published data, FTC and tenofovir have been shown to be present in human milk. There are no data on the presence of RPV in human milk. RPV has been shown to be present in rat milk.
• It is not known if the components of Complera affect milk production or have effects on the breastfed child.
• Because of the potential for: (1) HIV transmission (in HIV-negative infants); (2) developing viral resistance (in HIV-positive infants); and (3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving Complera.