TEMIXYS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TEMIXYS (TEMIXYS).
Temixys is a fixed-dose combination of tenofovir disoproxil fumarate (a nucleotide reverse transcriptase inhibitor) and lamivudine (a nucleoside reverse transcriptase inhibitor). Tenofovir diphosphate and lamivudine triphosphate inhibit HIV-1 reverse transcriptase by competing with natural substrates and causing DNA chain termination.
| Metabolism | Tenofovir DF is hydrolyzed to tenofovir and then phosphorylated to tenofovir diphosphate; minimal hepatic metabolism via CYP450 enzymes. Lamivudine is phosphorylated intracellularly to lamivudine triphosphate; minimally metabolized in the liver (5-10%) via oxidation. |
| Excretion | Biliary/fecal: approximately 70% unchanged; renal: less than 1% unchanged; about 30% as metabolites in feces. |
| Half-life | 41 hours (mean terminal elimination half-life); range 32-50 hours; supports once-daily dosing. |
| Protein binding | Greater than 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 3.3 L/kg (mean); indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability approximately 80%; with food, no significant change. |
| Onset of Action | Not applicable; oral tablet, no immediate clinical effect. |
| Duration of Action | Approximately 24 hours; consistent with once-daily dosing; clinical effect persists throughout dosing interval. |
Temixys (tenofovir disoproxil fumarate 300 mg / emtricitabine 200 mg) fixed-dose combination: one tablet orally once daily with or without food.
| Dosage form | TABLET |
| Renal impairment | Not recommended if CrCl < 30 mL/min. For CrCl 30–49 mL/min: administer one tablet every 48 hours. For CrCl ≥ 50 mL/min: standard dose. |
| Liver impairment | No dose adjustment required for mild or moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use caution. |
| Pediatric use | Approved for pediatric patients weighing ≥ 35 kg with adequate renal function: one tablet orally once daily. Not recommended for weight < 35 kg due to inability to adjust individual components. |
| Geriatric use | No specific dose adjustment recommended; select dose with caution due to higher frequency of decreased renal function, monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TEMIXYS (TEMIXYS).
| Breastfeeding | No human data on transmission via breast milk. Tenofovir alafenamide and emtricitabine are excreted in rat milk; in humans, tenofovir disoproxil fumarate has M/P ratio of 0.5-1.0. Because of potential HIV transmission and adverse effects in nursing infants, breastfeeding is not recommended. |
| Teratogenic Risk | Teratogenic risk not fully characterized; insufficient human data. In animal studies, no teratogenic effects observed at clinically relevant exposures. For HIV/HBV treatment, avoid use in first trimester unless benefit outweighs risk; if used, monitor for neural tube defects. Second and third trimester risks are low but data limited. |
■ FDA Black Box Warning
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs. Post-treatment acute exacerbations of hepatitis B have been reported in patients co-infected with HIV-1 and HBV who discontinued lamivudine or tenofovir DF. Hepatic function should be monitored closely in these patients.
| Serious Effects |
["Hypersensitivity to tenofovir, lamivudine, or any component of the formulation","Concomitant use with drugs containing tenofovir disoproxil fumarate, tenofovir alafenamide, lamivudine, or emtricitabine","Concomitant use with adefovir dipivoxil"]
| Precautions | ["Lactic acidosis and severe hepatomegaly with steatosis","Exacerbation of hepatitis B upon discontinuation","New onset or worsening renal impairment","Decrease in bone mineral density","Immune reconstitution syndrome","Fat redistribution/accumulation"] |
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| Fetal Monitoring | Monitor maternal renal function, liver function, and HIV/HBV viral load. Perform fetal ultrasound for neural tube defects if exposed in first trimester. Assess infant for adverse effects including renal and bone toxicity if maternal use during pregnancy. |
| Fertility Effects | No published human studies on fertility. In animal studies, no impairment of fertility or reproductive performance at up to 3.3 times human exposure for tenofovir alafenamide and emtricitabine. |