AccessPak For HIV PEP Expanded With Viracept
AccessPak For HIV PEP Expanded With Viracept 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.
Nelfinavir is a selective, competitive, reversible HIV protease inhibitor. It inhibits HIV-1 protease preventing the cleavage of the gag-pol polyprotein resulting in the production of noninfectious virus.
Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
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 | AccessPak For HIV PEP Expanded With Viracept |
| Generic | Emtricitabine + nelfinavir + tenofovir |
| Weight | + |
| Type | Oral kit |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| 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.
Nelfinavir is used for the treatment of HIV infection when antiretroviral therapy is warranted
This is used for the treatment of:
- Chronic hepatitis B virus infection in adults
- HIV infected adults in combination with other anti retroviral agents
AccessPak For HIV PEP Expanded With Viracept 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) InfectionHuman Immunodeficiency Virus Type 1 (HIV-1) Infection
How AccessPak For HIV PEP Expanded With Viracept 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.
Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
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
AccessPak For HIV PEP Expanded With Viracept dosage
Adults: The recommended dose is 1250 mg (five 250 mg tablets) twice daily or 750 mg (three 250 mg tablets) three times daily. Nelfinavir should be taken with a meal. Antiviral activity is enhanced when Nelfinavir is administered in combination with nucleoside analogues. Therefore, it is recommended that Nelfinavir should be used in combination with nucleoside analogues.
Paediatric patients (2-13 years): The recommended oral dose of Nelfinavir for paediatric patients 2 to 13 years of age is 20-30 mg/kg per dose, three times daily with a meal.
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 safety of Nelfinavir was studied in over 1500 patients who received drug either alone or in combination with nucleoside analogues. The majority of adverse events were of mild intensity. The most frequently reported adverse event among patients receiving Nelfinavir was diarrhoea, which was generally of mild to moderate intensity. Adverse events occurring in less than 2% of patients receiving Nelfinavir in all phase II/III clinical trials and considered at least possibly related or of unknown relationship to treatment and of at least moderate severity are listed below.
General: Abdominal pain, accidental injury, allergic reaction, asthenia, back pain, fever, headache, malaise, pain and redistribution/accumulation of body fat.
Digestive system: Anorexia, dyspepsia, epigastric pain, gastrointestinal bleeding, hepatitis, mouth ulceration, pancreatitis and vomiting.
Haemic/Lymphatic system: Anaemia, leukopenia and thrombocytopenia.
Metabolic/Nutritional: Increase in alkaline phosphate, amylase, creatinine phosphokinase, lactic dehydrogenase, SGOT, SGPT and g glutamyl transpeptidase, hyperlipaemia, hyperuricaemia, hyperglycaemia, hypoglycaemia, dehydration and liver function tests abnormal.
Musculoskeletal system: Arthralgia, arthritis, cramps, myalgia, myasthenia and myopathy.
Nervous system: Anxiety, depression, dizziness, emotional lability, hyperkinesia, insomnia, migraine, paraesthesia, seizures, sleep disorder, somnolence and suicide ideation.
Respiratory system: Dyspnoea, pharyngitis, rhinitis and sinusitis.
Skin/Appendages: Dermatitis, folliculitis, fungal dermatitis, maculopapular rash, pruitus, sweating, and urticaria.
Ophthalmic: Acute iritis and eye disorder.
Urogenital system: Kidney calculas, sexual dysfunction.
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.
Oral LD50 is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.
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
Nelfinavir should not be administered concurrently with Terfenadine, Astemizole, Cisapride, Triazolam, Midazolam, Ergot derivatives, Amiodarone or Quinidine because Nelfinavir may affect the hepatic metabolism of these drugs and create potential for serious and/or life-threatening adverse events. New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycaemia have been reported during post-marketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycaemic agents for treatment of these events. In some cases diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycaemia persisted in some cases.
General: Nelfinavir is principally metabolised by the liver. Therefore, caution should be exercised when administering this drug to patients with hepatic impairment.
Haemophilia: There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis, in patients with haemophilia type A and B treated with protease inhibitors. In some patients, additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. A causal relationship has not been established.
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
Reduced levels/effects with antacids, phenobarbital, carbamazepine, aminoglutethimide, phenytoin, rifampicin, nafcillin, nevirapine, omeprazole, nevirapine. Increased serum levels/effects with azole antifungal agents, cimetidine, efavirenz. Increased serum levels/effects of azithromycin, calcium channel blockers, clarithromycin, corticosteroids (e.g. fluticasone), mirtazapine, nateglinide, nefazodone, ciclosporin, sirolimus, tacrolimus, venlafaxine, eplerinone, fentanyl, atorvastatin, phosphodiesterase-5 (PDE-5) inhibitors, rifabutin, trazodone, TCAs. Reduced serum levels/effects of hormonal contraceptives, methadone, theophylline derivatives.
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.
- 2 to 7 L/kg
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
Well absorbed following oral administration.
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.
3.5 - 5 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.
The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1–2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.
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 Category B. There are no adequate and well controlled studies in pregnant women.
Lactation: The US Public Health Service Centers for Disease Control and Prevention advises HIV-infected women not to breast-feed to avoid postnatal transmission of HIV to a child.
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
Nelfinavir is contraindicated in patients with clinically significant hypersensitivity to any of its components. Co-administration of Avifix is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening adverse events
Tenofovir is contraindicated in patients with known hypersensitivity to Tenofovir or any component of the product.
Special Warning
Paediatric use: The safety, effectiveness and pharmacokinetics of Nelfinavir have not been evaluated in paediatric patients below the age of 2 years.
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 at 15-30° C
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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