Triumeq
Triumeq
Generic Name
Triumeq
Brand Names
for the once‑daily fixed‑dose combination antiretroviral tablet containing emtricitabine, tenofovir alafenamide (TAF), and rilpivirine. It is indicated for treatment‑naïve adult patients with HIV‑1 infection and is available in a single‑tablet formulation (200 mg emtricitabine/25 mg TAF/25 mg rilpivirine).
Mechanism
- Emtricitabine: Nucleoside reverse‑transcriptase inhibitor (NRTI) that incorporates into viral DNA, causing chain termination.
- Tenofovir alafenamide (TAF): Prodrug of tenofovir; after intracellular conversion to tenofovir diphosphate, it competes with dATP for reverse‑transcriptase, leading to incomplete DNA replication.
- Rilpivirine: Non‑nucleoside reverse‑transcriptase inhibitor (NNRTI) that binds to a hydrophobic pocket adjacent to the active site of reverse transcriptase, inducing a conformational change that inhibits polymerase activity.
The triple‑agent regimen targets multiple enzymatic steps of the HIV life cycle, providing potent viral suppression while limiting drug‑drug interactions.
Pharmacokinetics
| Parameter | Key Points | Comments |
| Absorption | Oral, bioavailability ~70 % (TAF). Rilpivirine absorption is pH‐dependent; optimum plasma levels require ingestion with a regular meal. | Food increases rilpivirine exposure significantly. |
| Distribution | Emtricitabine: Vd ~ 0.35 L/kg; TAF: low plasma levels, high intracellular concentration in peripheral blood mononuclear cells (PBMCs). Rilpivirine: Vd ~ 121 L; highly protein‑bound (≈99 %). | Rilpivirine has a long terminal half‑life (~40–50 h). |
| Metabolism | Emtricitabine: minimal hepatic metabolism; excreted unchanged. TAF: slowly hydrolyzed to tenofovir, then phosphorylated. Rilpivirine: hydroxylation via CYP3A4. | Rilpivirine is a moderate CYP3A4 substrate; caution with strong inhibitors/inducers. |
| Elimination | Emtricitabine & TAF/tenofovir: primarily renal (≈90 %). Rilpivirine: fecal elimination (~70 %) and renal (~20 %). | CrCl ≥ 30 mL/min required for safe use. |
| Half‑life | Emtricitabine: ~10 h; TAF/tenofovir diphosphate: ~60–70 h in PBMCs; Rilpivirine: ~44 h. | Allows once‑daily dosing. |
Indications
- Treatment‑naïve adults with HIV‑1 infection where a single‑tablet regimen is appropriate.
- Maintenance therapy for adults with virologic suppression (HIV‑1 RNA < 50 copies/mL) who require continuing therapy (specifically for this fixed‑dose combo).
*Contraindicated in patients with severe hepatic impairment (baseline ALT ≥ 5× ULN) or in those with CrCl < 30 mL/min.*
Contraindications
- Contraindicated:
- Severe hepatic impairment.
- CrCl < 30 mL/min.
- Known hypersensitivity to any component.
- Warnings:
- Hyperbilirubinemia and cholestatic liver injury; monitor LFTs during first few weeks.
- Renal impairment: monitor creatinine and eGFR.
- Hepatic enzyme elevations can mimic those of other NNRTIs; differentiate from end‑stage liver disease.
- Drug interactions:
- Avoid with strong CYP3A4 inducers (e.g., rifampin) and inhibitors (e.g., ketoconazole).
- Rilpivirine is affected by gastric pH; avoid PPIs when possible.
- TAF reduces bone mineral density modestly; baseline and periodic DEXA are recommended.
Dosing
- Standard dose: 1 tablet orally once daily, taken at the same time each day.
- With Food: At least 1 hour after a regular meal or anytime if concerns about rilpivirine absorption (e.g., antacids or acid‑suppressive therapy).
- Missed dose: Take as soon as remembered, unless > 12 h has passed; then skip and resume routine dosing.
- Switching: If changing from other regimens, consider pharmacodynamic overlap with TDF/FTC/EFV/EFV‑based regimens; overlap may be needed to avoid viral breakthrough.
Adverse Effects
- Common (≤ 10 % incidence):
- Nausea, dyspepsia, constipation.
- Headache, rash.
- Mild hyperbilirubinemia.
- Serious (≤ 1 % incidence):
- Hepatotoxicity (elevated ALT/AST, cholestatic jaundice).
- Acute kidney injury (rhabdomyolysis).
- Severe hypersensitivity reactions (rash, DRESS).
- Decreased bone mineral density (especially after ≥ 1 yr).
Monitoring
| Parameter | Frequency | Rationale |
| HIV‑1 RNA (VL) | 4 weeks, then every 12 weeks | Ensure viral suppression |
| CD4+ T‑cell count | Every 3–6 months | Immune recovery |
| Hepatic panel | Baseline, 1–2 weeks, then 4 weeks, then every 3–6 months | Detect hepatotoxicity |
| Creatinine & eGFR | Baseline, 1 week, then every 3 months | Monitor renal function |
| Bone mineral density | Baseline, then annually if risk factors | Detect osteoporosis |
| Bilirubin | Baseline, 2 weeks, then 4 weeks | Identify isolated hyperbilirubinemia |
Clinical Pearls
- Food Timing: Rilpivirine’s bioavailability is maximized with a regular meal; if a patient accidentally misses a dose with food, a single last dose can be taken > 2 h after a high‑fat meal to achieve adequate exposure.
- Drug‑Drug Interactions: Avoid concurrent use of PPIs in the same dose window each day; a separation of ≥ 8 h is recommended or use a H2 blocker instead.
- Renal Safety: TAF’s lower plasma tenofovir exposure reduces nephrotoxicity compared with tenofovir disoproxil fumarate (TDF), making Triumeq a preferred option in patients with mild-to‑moderate kidney disease.
- Resistance Consideration: Patients with known K103N or Y181C mutations (conferring resistance to earlier NNRTIs) may still be candidates, as rilpivirine retains activity; however, resistance testing is advised before initiation.
- Adherence: The single‑tablet once‑daily regimen correlates with higher adherence and lower virologic failure compared with co‑administration of separate NRTI/NNRTI tables.
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• *This drug card draws from current prescribing information (FDA label, 2025) and recent peer‑reviewed pharmacology reviews. Always refer to the latest product insert for updates.*