COMPLERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COMPLERA (COMPLERA).
Emtricitabine and tenofovir disoproxil fumarate are nucleoside reverse transcriptase inhibitors (NRTIs); rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Rilpivirine inhibits HIV-1 replication by non-competitive inhibition of reverse transcriptase. Emtricitabine and tenofovir are phosphorylated to active metabolites that compete with natural substrates and incorporate into viral DNA, causing chain termination.
| Metabolism | Rilpivirine is primarily metabolized by CYP3A4. Emtricitabine is not extensively metabolized; undergoes oxidation and glucuronidation. Tenofovir disoproxil fumarate is converted to tenofovir by esterases, then phosphorylated intracellularly; not significantly metabolized by CYP enzymes. |
| Excretion | Renal: 70% unchanged (emtricitabine), 6% unchanged (tenofovir), 1% unchanged (rilpivirine). Fecal: 85% (rilpivirine, largely unchanged). Biliary: minor for rilpivirine. |
| Half-life | Rilpivirine: 45 hours; Emtricitabine: 10 hours; Tenofovir: 17 hours. Clinical context: supports once-daily dosing. |
| Protein binding | Rilpivirine: 99.7% (albumin); Emtricitabine: <4%; Tenofovir: <7%. |
| Volume of Distribution | Rilpivirine: 152 L (≈2.2 L/kg); Emtricitabine: 1.4 L/kg; Tenofovir: 1.3 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: rilpivirine ~100% (with fatty meal), emtricitabine 93%, tenofovir disoproxil fumarate 25% (parent tenofovir). |
| Onset of Action | Not applicable; continuous viral suppression over 2-4 weeks. |
| Duration of Action | 24 hours (once-daily dosing); consistent antiviral effect over dosing interval. |
Each tablet contains 200 mg emtricitabine, 25 mg rilpivirine, and 300 mg tenofovir disoproxil fumarate. One tablet orally once daily with a meal.
| Dosage form | TABLET |
| Renal impairment | Not recommended for patients with creatinine clearance < 50 mL/min. No dose adjustment required for CrCl ≥ 50 mL/min. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Contraindicated in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not recommended in pediatric patients < 12 years old or weighing < 35 kg. For patients ≥ 12 years and ≥ 35 kg: one tablet orally once daily with a meal. |
| Geriatric use | No specific dose adjustment recommended. Monitor renal function due to age-related decline and potential for tenofovir-associated nephrotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COMPLERA (COMPLERA).
| Breastfeeding | It is not recommended to breastfeed while taking COMPLERA due to the potential for HIV transmission and adverse effects in the infant. The M/P ratio is not available for the combination. Emtricitabine and tenofovir are excreted in human milk; rilpivirine is likely excreted. |
| Teratogenic Risk | COMPLERA (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) is classified as Pregnancy Category B. No increased risk of major birth defects has been observed in first trimester exposures based on data from the Antiretroviral Pregnancy Registry. However, tenofovir disoproxil fumarate has been associated with reduced fetal growth and bone mineral density in infants. Monitoring for HIV transmission prophylaxis is recommended. |
■ FDA Black Box Warning
WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate and emtricitabine. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV and have discontinued emtricitabine or tenofovir disoproxil fumarate. Hepatic function should be monitored closely in these patients. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
| Serious Effects |
["Combination with dofetilide, rifampin, rifapentine, St. John's wort, dexamethasone (multiple doses), proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole)","Combination with drugs that significantly decrease rilpivirine concentration (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin) unless known benefit outweighs risk"]
| Precautions | ["Lactic acidosis/severe hepatomegaly with steatosis","Severe acute exacerbation of hepatitis B in HBV-coinfected patients after discontinuation","New onset or worsening renal impairment: increased risk with tenofovir","Decreases in bone mineral density reported with tenofovir","Immune reconstitution syndrome","Drug interactions: drugs that induce or inhibit CYP3A4 may affect rilpivirine concentrations; concomitant use with proton pump inhibitors is contraindicated; H2-receptor antagonists and antacids require staggered administration"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal HIV RNA levels, CD4 count, hepatic function, renal function (serum creatinine, urine glucose and protein), and fetal growth via ultrasound. Assess infant for HIV status, bone density (if long-term exposure), and renal function after birth. |
| Fertility Effects | No known adverse effects on male or female fertility from animal studies. In humans, no significant reproductive impact reported, but underlying HIV disease may affect fertility. |