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. |
| Molecular Weight | Emtricitabine: 247.24 Da; Tenofovir disoproxil: 635.53 Da; Rilpivirine: 366.42 Da |
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 | No adequate studies in humans; animal studies show no teratogenicity at therapeutic doses; use only if benefit outweighs risk. |
| 2nd trimester | No adequate studies; no evidence of fetal harm in animal studies; consider if maternal benefit justifies potential fetal risk. |
| 3rd trimester | No adequate studies; no known neonatal adverse effects; may be used if indicated. |
Clinical note
Comprehensive clinical and safety monograph for COMPLERA (COMPLERA).
| Placental transfer | Emtricitabine and tenofovir cross the placenta; riipivirine placental transfer not well studied. |
| Breastfeeding | Emtricitabine and tenofovir are excreted in human milk; riipivirine is excreted in animal milk. Potential for HIV transmission via breastfeeding exists. Avoid breastfeeding in HIV-infected women in developed settings where formula is safe. |
■ 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 |
Severe hepatic impairment (Child-Pugh Class C)Concomitant use with strong CYP3A4 inducers (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, St. John's wort)History of hypersensitivity to any component
| 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…
| Lactation Rating | L4 |
| 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. |
| 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. |
| Food/Dietary | COMPLERA must be taken with a meal to ensure adequate absorption of rilpivirine. A protein-rich snack or a full meal is sufficient; avoid taking on an empty stomach. No specific food restrictions, but high-fat meals may slightly increase absorption; consistency is key. Avoid alcohol as it may worsen liver strain. |
| Clinical Pearls | COMPLERA (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) is a fixed-dose combination for HIV-1 infection. Must be taken with a meal to ensure adequate rilpivirine absorption. Avoid coadministration with proton pump inhibitors; separate antacids by at least 2 hours. Monitor renal function due to tenofovir DF risk. Not recommended if CrCl <50 mL/min. Screen for hepatitis B virus (HBV) before starting; if HBV coinfected, monitor for flare upon discontinuation. Rilpivirine should not be used with HIV-1 RNA >100,000 copies/mL or CD4 <200 cells/μL at initiation. |
| Patient Advice | Take COMPLERA exactly as prescribed, once daily with a meal. Missing doses can lead to drug resistance. · Do not take with proton pump inhibitors (PPIs) like omeprazole. Antacids should be taken at least 2 hours before or after COMPLERA. · Avoid medications or herbal supplements that may interact; discuss all new drugs with your healthcare provider. · Get regular renal function tests; stay hydrated to prevent kidney problems. · Inform your doctor if you have hepatitis B virus infection; stopping COMPLERA may cause severe liver inflammation. · Use effective contraception if applicable; COMPLERA does not prevent pregnancy or other infections. · Report any symptoms of liver problems: yellowing skin/eyes, dark urine, abdominal pain, or unusual tiredness. |