Complera Access
Complera Access Uses, Dosage, Side Effects, Food Interaction and all others data.
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) indicated for the treatment of HIV infection in adults or combined with tenofovir alafenamide for the prevention of HIV-1 infection in high risk adolescents and adults. Emtricitabine is a cytidine analogue. The drug works by inhibiting HIV reverse transcriptase, preventing transcription of HIV RNA to DNA.
Emtricitabine was granted FDA approval on 2 July 2003.
Emtricitabine is a cytidine analog that competes with the natural substrate of HIV-1 reverse transcriptase to be incorporated into newly formed DNA, terminating its transcription. It is administered once daily so it has a long duration of action. Patients should be counselled regarding the risk of lactic acidosis and hepatomegaly with steatosis.
Tenofovir Disoproxil Fumarate, an acyclic nucleotide analogue of adenosine monophosphate, is a pro-drug of Tenofovir. It shows activity against hepatitis B virus polymerase and HIV reverse transcriptase after phosphorylation to the active diphosphate form. Tenofovir diphosphate inhibits viral polymerase (reverse transcriptase) by directly competing with the natural substrate deoxyribonucleotide and by causing DNA chain termination after its incorporation into viral DNA.
Tenofovir has been shown to be highly effective in patients that have never had an antiretroviral therapy and it seemed to have lower toxicity than other antivirals such as stavudine. In phase 3 clinical trials, tenofovir presented a similar efficacy than efavirenz in treatment-naive HIV patients. In hepatitis B infected patients, after one year of tenofovir treatment, the viral DNA levels were undetectable.
| Trade Name | Complera Access |
| Generic | Emtricitabine + Rilpivirine Hydrochloride + Tenofovir |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | USA |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Emtricitabine is a nucleoside reverse transcriptase inhibitor used for the treatment and prophylaxis of HIV.
Emtricitabine is indicated in combination with other medications for the treatment of HIV-1 infections; treatment of HIV-1 infections in pediatric patients 25-35kg, treatment of HIV-1 infections in adult patients ≥35kg, for pre exposure prophylaxis of HIV-1 in adolescent and adult patients excluding those who have receptive vaginal sex; treatment of HIV-1 infections in pediatric and adult patients ≥17kg, pre exposure prophylaxis in adolescents and adults ≥35kg; treatment of HIV-1 in patients ≥12 years and ≥35kg; treatment of HIV-1 in patients weighing ≥35kg; treatment of HIV-1 in patients weighing ≥25kg; and treatment of HIV-1 in patients weighing ≥40kg.
This is used for the treatment of:
- Chronic hepatitis B virus infection in adults
- HIV infected adults in combination with other anti retroviral agents
Complera Access is also used to associated treatment for these conditions: HIV Transmission, Human Immunodeficiency Virus (HIV) Infections, Human Immunodeficiency Virus Type 1 (HIV-1), Human Immunodeficiency Virus Type 1 (HIV-1) Infection
How Complera Access works
Emtricitabine is a cytidine analog which, when phosphorylated to emtricitabine 5'-triphosphate, competes with deoxycytidine 5'-triphosphate for HIV-1 reverse transcriptase. As HIV-1 reverse transcriptase incorporates emtricitabine into forming DNA strands, new nucleotides are unable to be incorporated, leading to viral DNA chain termination. Inhibition of reverse transcriptase prevents transcription of viral RNA into DNA, therefore the virus is unable to incorporate its DNA into host DNA and replicate using host cell machinery. This reduces viral load.
Once tenofovir is activated by a bi-phosphorylation it acts as an antiviral acyclic nucleoside phosphonate. It is a potent inhibitor of the viral reverse transcriptase with an inhibitory constant of approximately 0.022 micromolar.
Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis. All these activities are attained by its competition with deoxyadenosine 5'-triphosphate in the generation of new viral DNA. Once tenofovir is incorporated in the chain, it induces a chain termination which in order inhibits viral replication. The safety of tenofovir relies on its low affinity towards the cellular DNA polymerase including the mitochondrial DNA polymerase gamma.
Dosage
Complera Access dosage
The recommended dose of Tenofovir in chronic hepatitis B virus infection in adults 18 years of age and older with adequate renal function is 300 mg once daily with or without food.
Side Effects
The most common side effects are nausea, vomiting, diarrhea and flatulence.
Toxicity
The LD50 of emtricitabine is not readily available.[9019,L9818]
Symptoms of emtricitabine toxicity include hepatotoxicity with steatosis, as well as lactic acidosis. Treat overdose with symptomatic and supportive measures, including hemodialysis.
There haven't been reports regarding the LD50 of the parent compound nor the effects of an overdose. However, based on the reports with the derivative that most rapidly transforms into tenofovir, tenofovir disoproxil, it is recommended to monitor overdose patients. As well, it is widely known that tenofovir is efficiently removed by hemodialysis.
Administration of high doses of tenofovir has been reported to produce bone toxicity reported as osteomalacia and reduced bone mineral density and to produce some degree of renal toxicity.
To know more about the carcinogenicity and mutagenic potential of tenofovir, as well as the effect on fertility, please visit the drug entries for the derivatives tenofovir disoproxil and tenofovir alafenamide.
Precaution
Co-administration with other drugs: Tenofovir should not be administered concurrently with Emtricitabine & Tenofovir combination or Adefovir Dipivoxil.
Lactic Acidosis & Severe Hepatomegaly with Steatosis: Though the risk of occurrence of lactic acidosis is low for Tenofovir, treatment should be suspended in any patient who develops lactic acidosis or hepatotoxicity.
Exacerbation of hepatitis after discontinuation of treatment: Discontinuation of Tenofovirtherapy may be associated with severe acute exacerbation of hepatitis.
Interaction
Co-administration of Tenofovir with anti-retroviral, entecavir, lamivudine, methadone, oral contraceptives, ribavirin and tacrolimus did not result in significant drug interactions. The effects of co-administration of Tenofovir with other drugs that are renally eliminated or are known to affect renal function have not been evaluated.
Volume of Distribution
The apparent central volume of distribution is 42.3L and the peripheral volume of distribution is 55.4L.
Accumulation of tenofovir in plasma is related to the presence of nephrotoxic effects. It is reported that tenofovir presents a volume of distribution of 0.813 L/kg.
Elimination Route
Emtricitabine reaches a Cmax of 1.8±0.7µg/mL with a Tmax of 1-2 hours, and has an AUC of 10±3.1µg*hr/mL. The bioavailability of emtricitabine capsules is 93% and the bioavailability of the oral solution is 75%. Taking emtricitabine with food decreases the Cmax by 29%.[L9019
Tenofovir as the active moiety presents a very low bioavailability when orally administered. Hence, the administration of this active agent is required to be under its two prodrug forms, tenofovir disoproxil and tenofovir alafenamide. This reduced absorption is suggested to be related to the presence of two negative charges among its structure. This negative charge limits its cellular penetration, and its passive diffusion across cellular membranes and intestinal mucosa hindering its availability for oral administration.
Intravenous tenofovir has been shown to produce a maximum plasma concentration of 2500 ng/ml with an AUC of 4800 ng.h/ml.
Half Life
The half life of emtricitabine is approximately 10 hours.
The reported half-life of tenofovir is of 32 hours.
Clearance
Emtricitabine has an apparent elimination rate of 15.1L/h. This rate is closely linked to creatinine clearance.
The clearance of tenofovir is highly dependent on the patient renal stage and hence the clearance rate in patients with renal impairment is reported to be of 134 ml/min while in patients with normal function the clearance rate can be of 210 ml/min.
Elimination Route
Emtricitabine is 86% recovered in the urine and 14% recovered in feces. 13% of the dose is recovered in the urine as metabolites; 9% as 3'-sulfoxide diastereomers and 4% as 2'-O-glucuronide.
Tenofovir is eliminated in the urine by tubular secretion and glomerular filtration. The elimination of this compound is driven by the activity of the human organic anion transporters 1 and 3 and its secretion is mainly ruled by the activity of the multidrug resistance-associated protein 4.
Pregnancy & Breastfeeding use
Pregnancy: Pregnancy category B. It should be used during pregnancy only if clearly needed.
Lactation: It is not known whether it is excreted in human milk. Mothers should be instructed not to breast feed if they are taking Tenofovir.
Contraindication
Tenofovir is contraindicated in patients with known hypersensitivity to Tenofovir or any component of the product.
Special Warning
Pediatric use: Safety and effectiveness of Tenofovir in pediatric patients below the age of 18 years have not been established.Geriatrics use: Clinical studies of Tenofovir did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. But care should be taken in dose selection, and it may be useful to monitor renal function.Renal Impairment: Haemodialysis patients: 300 mg once every 7 days or after a cumulative total of 12 hr of dialysis.
- CrCl (10-29 mL/min): 300 mg 72-96 hrly.
- CrCl (30-49 mL/min): 300 mg 48 hrly.
Hepatic impairment
: No dose adjustment is required in patients with hepatic impairment.
Acute Overdose
There is no experience of Tenofovir overdose reported in patients
Storage Condition
Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.
Innovators Monograph
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