SYMFI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMFI (SYMFI).
Symfi is a combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate. Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds reversibly to HIV-1 reverse transcriptase, causing a conformational change and inhibiting RNA-directed DNA polymerase activity. Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that is phosphorylated intracellularly to its active triphosphate metabolite, which competes with deoxycytidine triphosphate for incorporation into viral DNA, causing chain termination. Tenofovir disoproxil fumarate is an acyclic nucleotide analog NRTI that, after hydrolysis to tenofovir and subsequent phosphorylation, inhibits HIV reverse transcriptase by competing with deoxyadenosine triphosphate and causing DNA chain termination.
| Metabolism | Efavirenz is primarily metabolized by CYP2B6 and to a lesser extent by CYP3A4. Lamivudine is minimally metabolized; it undergoes intracellular phosphorylation to its active triphosphate form. Tenofovir disoproxil fumarate is hydrolyzed to tenofovir and then phosphorylated to tenofovir diphosphate; tenofovir is eliminated renally by glomerular filtration and active tubular secretion. |
| Excretion | Approximately 90% of the administered dose is excreted unchanged in the urine via glomerular filtration and tubular secretion. Less than 5% is eliminated via feces. |
| Half-life | Terminal elimination half-life is approximately 8-12 hours in patients with normal renal function. This supports twice-daily dosing in clinical practice. |
| Protein binding | Protein binding is approximately 10%. Primarily bound to albumin. |
| Volume of Distribution | Volume of distribution is approximately 1.0-1.5 L/kg, indicating distribution into total body water. |
| Bioavailability | Bioavailability is 100% following intravenous administration. |
| Onset of Action | Intravenous administration: clinical effect observed within 15-30 minutes. |
| Duration of Action | Duration of action is approximately 8-12 hours, consistent with the dosing interval. |
SYMFI (efavirenz/lamivudine/tenofovir disoproxil fumarate) fixed-dose combination: one tablet (600 mg efavirenz/300 mg lamivudine/300 mg tenofovir disoproxil fumarate) orally once daily on an empty stomach, preferably at bedtime.
| Dosage form | TABLET |
| Renal impairment | Not recommended for patients with creatinine clearance (CrCl) <50 mL/min. For CrCl 50-80 mL/min, no dose adjustment needed; monitor renal function. For CrCl <50 mL/min, use individual components with appropriate dose adjustments (lamivudine and tenofovir disoproxil fumarate require dose reduction; efavirenz does not require adjustment). |
| Liver impairment | Contraindicated in Child-Pugh Class C. For Child-Pugh Class A or B, no dose adjustment for lamivudine or tenofovir; efavirenz should be used with caution as increased exposure may occur. No specific dose reduction guidelines; consider monitoring liver function and efavirenz plasma levels. |
| Pediatric use | Approved for children weighing at least 40 kg: one tablet (600/300/300 mg) orally once daily. For children <40 kg, use individual components with weight-based dosing: efavirenz 600 mg (or adjusted based on weight per guidelines), lamivudine 300 mg, tenofovir disoproxil fumarate 300 mg; not recommended for children <3 years or <10 kg. |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYMFI (SYMFI).
| Breastfeeding | Breastfeeding is not recommended for mothers with HIV to avoid postnatal transmission. Efavirenz and tenofovir are excreted in human milk; M/P ratio not well-defined. Emtricitabine M/P ratio is approximately 0.06. |
| Teratogenic Risk | SYMFI (efavirenz/emtricitabine/tenofovir disoproxil fumarate) is contraindicated in the first trimester due to neural tube defects. In second and third trimesters, risk is lower but requires careful risk-benefit assessment. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued lamivudine or tenofovir disoproxil fumarate, components of Symfi. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment.
| Serious Effects |
["Hypersensitivity to efavirenz, lamivudine, tenofovir disoproxil fumarate, or any component of the formulation.","Coadministration with drugs that are highly dependent on CYP2B6 or CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., astemizole, terfenadine, dihydroergotamine, ergotamine, ergonovine, methylergonovine, cisapride, pimozide, midazolam, triazolam, or St. John's wort)."]
| Precautions | ["Hepatotoxicity: Severe hepatotoxicity including hepatic steatosis and fatalities reported; monitor liver enzymes.","Lactic acidosis and severe hepatomegaly with steatosis: Reported with nucleoside analogs, including lamivudine and tenofovir disoproxil fumarate; discontinue if clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity occur.","Exacerbation of hepatitis B: See black box warning.","Renal impairment: Tenofovir is associated with renal toxicity; monitor renal function and adjust dose in patients with creatinine clearance <50 mL/min.","Bone effects: Decreased bone mineral density reported with tenofovir; assess if history of bone fracture or risk factors.","Central nervous system symptoms: Including dizziness, insomnia, impaired concentration, and abnormal dreams; may impair ability to drive or operate machinery.","Psychiatric symptoms: Severe depression, suicidal ideation, and aggressive behavior reported.","Immune reconstitution syndrome: May occur during initial treatment; monitor for inflammatory responses to opportunistic infections.","Lipid elevation: Increases in total cholesterol and triglycerides reported; monitor lipid levels.","Convulsions: Use with caution in patients with a history of seizures."] |
Loading safety data…
| No specific dose adjustments, but use with caution due to age-related renal impairment (CrCl decline). Monitor renal function and adjust components as per renal guidelines. Increased risk of CNS side effects from efavirenz; consider bedtime dosing and monitoring for dizziness, impaired concentration, and somnolence. |
| Monitor maternal HIV viral load, CD4 count, hepatic and renal function. Fetal ultrasound screening for neural tube defects if exposed in first trimester. Consider therapeutic drug monitoring. |
| Fertility Effects | No evidence of significant impact on fertility. Efavirenz may cause ovarian failure in animal studies; human data limited. Men: no known effect on spermatogenesis. |