Odivir

Odivir Uses, Dosage, Side Effects, Food Interaction and all others data.

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.

Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Didanosine is a hypoxanthine attached to the sugar ring, unlike other nucleoside analogues. Didanosine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial. Didanosine has weak acid stability and therefore, it is often combined with an antacid.

Efavirenz, a synthetic antiretroviral agent, is a non- nucleoside reverse transcriptase inhibitor. While Efavirenz is pharmacologically related to other non nucleoside reverse transcriptase inhibitors, Efavirenz differs structurally from these drugs and also differs structurally from other currently available anti-retroviral agents.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against HIV-1. It blocks the RNA- and DNA-dependent polymerase activities including HIV-1 replication.

Efavirenz (dideoxyinosine, ddI) is an oral non-nucleoside reverse transcriptase inhibitor (NNRTI). It is a synthetic purine derivative and, similar to zidovudine, zalcitabine, and stavudine. Efavirenz was originally approved specifically for the treatment of HIV infections in patients who failed therapy with zidovudine. Currently, the CDC recommends that Efavirenz be given as part of a three-drug regimen that includes another nucleoside reverse transcriptase inhibitor (e.g., lamivudine, stavudine, zidovudine) and a protease inhibitor or efavirenz when treating HIV infection.

Lamivudine is a synthetic nucleoside analogue. Lamivudine is phosphorylated intracellularly to lamivudine triphosphate. Incorporation of the monophosphate form into viral DNA occurs by hepatitis B virus (HBV) polymerase. As a result DNA chain is terminated. Lamivudine triphosphate also inhibits the RNA and DNA-dependent DNA polymerase activities of HIV-1 reverse transcriptase (RT). Lamivudine triphosphate is a very weak inhibitor of mammalian alpha, beta, and gamma-DNA polymerases.

Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV) to disrupt viral DNA synthesis. When phosphorylated, lamivudine can form active metabolites that compete for incorporation into viral DNA. Via DNA incorporation, lamivudine metabolites competitively inhibit the activity of the HIV reverse transcriptase enzyme and act as a chain terminator of DNA synthesis. Due to the lack of a 3'-OH group, incorporated nucleoside analogues prevent the formation of a 5' to 3' phosphodiester linkage that is essential for DNA chain elongation.

Odivir
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Odivir
Generic	Efavirenz + Didanosine + Lamivudine
Weight	400mg, 300mg
Type	Kit
Therapeutic Class
Manufacturer	Cipla Limited
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Didanosine is a reverse transcriptase inhibitor used to treat HIV.

For use, in combination with other antiretroviral agents, in the treatment of HIV-1 infection in adults.

Efavirenz in combination with other antiretroviral agents is used for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV- RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long term suppression of HIVRNA with Efavirenz.

Lamivudine is used for the treatment of chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation.

Odivir is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) InfectionHuman Immunodeficiency Virus Type 1 (HIV-1) InfectionHepatitis B Chronic Infection, Human Immunodeficiency Virus (HIV) Infections

How Odivir works

Didanosine (ddI) is metabolized intracellularly by a series of cellular enzymes to its active moiety, dideoxyadenosine triphosphate (ddATP), which inhibits the HIV reverse transcriptase enzyme competitively by competing with natural dATP. It also acts as a chain terminator by its incorporation into viral DNA as the lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

Similar to zidovudine, efavirenz inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase). Antiviral activity of efavirenz is dependent on intracellular conversion to the active triphosphorylated form. The rate of efavirenz phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for synthesis of new virions. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virustatic and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated efavirenz, this action may nevertheless account for some of the drug's toxicity.

Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination.

Dosage

Odivir dosage

It is recommended that Efavirenz be taken on an empty stomach, preferably at bedtime.

Adults: The recommended dosage of Efavirenz is 600 mg orally, once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs).

Pediatric Patients: Following table describes the recommended dose of Efavirenz for pediatric patients 3 years of age or older and weighing between 10 and 40 kg. The recommended dosage of Efavirenz for pediatric patients weighing greater than 40 kg is 600 mg, once daily.

10 to <15 kg: 200 mg

15 to < 20 kg:250 mg

20 to < 25 kg: 300 mg

25 to < 32.5 kg:350 mg

32.5 to < 40 kg: 400 mg

40 kg: 600 mg

The recommended oral dose of Lamivudine for the treatment of chronic hepatitis B in adults is 100 mg once daily.

Side Effects

Rashes, psychiatric or CNS disturbances, amnesia, agitation, confusion, dizziness, vertigo, headache, euphoria, insomnia or somnolence, impaired concentration, abnormal thinking or dreaming, depersonalisation, convulsions, hallucinations, nausea, vomiting, diarrhoea, pancreatitis, fatigue, hepatic failure, photoallergic dermatitis; autoimmune disorders (e.g. Graves’ disease, polymyositis, Guillain-Barre syndrome), osteonecrosis. Accumulation or redistribution of body fat (lipodystrophy) including central obesity, peripheral and facial wasting, buffalo hump, breast enlargement, cushingoid appearance. Metabolic abnormalities e.g. hypercholesterolaemia, hyperglycaemia, hypertriglyceridaemia, hyperlactataemia, insulin resistance.

Several serious adverse events reported with lamivudine (lactic acidosis and severe hepatomegaly with steatosis, post treatment exacerbations of hepatitis B, pancreatitis, and emergence of viral mutants associated with reduced drug susceptibility and diminished treatment response). Malaise, fatigue, fever, ENT infections, sore throat, nausea, vomiting, abdominal discomfort, pain, diarrhea, myalgia, arthralgia, headache, skin rashes may occur. Lactic acidosis and severe hepatomegaly with steatosis, have been reported.

Toxicity

Side effects include pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia and hepatic dysfunction

The most common reported adverse reactions (incidence ≥15%) in adults were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough.

Precaution

Patient with history of seizures and psychiatric disorders; acute porphyria. Patients receiving voriconazole or rifampicin (weighing ≥50 kg). Discontinue if severe rash or fever develops. Moderate hepatic and severe renal impairment. Childn. Pregnancy.

Patients should be assessed before beginning treatment and during treatment with lamivudine by a physician experienced in the management of chronic hepatitis B.

Interaction

Additive CNS effects w/ psychoactive drugs. May alter plasma warfarin concentrations. May reduce plasma concentrations of HIV integrase inhibitors (e.g. dolutegravir), other HIV NNRTIs (e.g. etravirine), HMG-CoA reductase inhibitors (e.g. simvastatin). Plasma concentrations of efavirenz is increased and that of voriconazole is reduced when given concomitantly. Reduced plasma concentrations w/ rifampicin.

Trimethoprim 160 mg / Sulfamethoxazole 800 mg once daily has been shown to increase lamivudine exposure (AUC). The effect of higher doses of trimethoprim /sulfamethoxazole on lamivudine pharmacokinetics has not been investigated.

Volume of Distribution

Apparent volume of distribution, IV administration = 1.3 ± 0.4 L/kg. Volume of distribution was independent of dose and did not correlate with body weight.

Elimination Route

Rapidly absorbed (bioavailability 30-40%) with peak plasma concentrations appearing within 0.5 and 1.5 hrs.

Lamivudine was rapidly absorbed after oral administration in HIV-infected patients. Absolute bioavailability in 12 adult patients was 86% ± 16% (mean ± SD) for the 150-mg tablet and 87% ± 13% for the oral solution. The peak serum lamivudine concentration (Cmax) was 1.5 ± 0.5 mcg/mL when an oral dose of 2 mg/kg twice a day was given to HIV-1 patients. When given with food, absorption is slower, compared to the fasted state.

Half Life

30 minutes in plasma and more than 12 hours in intracellular environment.

40-55 hours

5 to 7 hours (healthy or HBV-infected patients)

Clearance

Renal clearance = 199.7 ± 56.9 mL/min [300 mg oral dose, healthy subjects]
Renal clearance = 280.4 ± 75.2 mL/min [single IV dose, HIV-1-infected patients]
Total clearance = 398.5 ± 69.1 mL/min [HIV-1-infected patients]

Elimination Route

Based on data from in vitro and animal studies, it is presumed that the metabolism of didanosine in man occurs by the same pathways responsible for the elimination of endogenous purines. Purines are eliminated by the kidneys.

Nearly all of the urinary excretion of the radiolabeled drug was in the form of metabolites.

The majority of lamivudine is eliminated unchanged in urine by active organic cationic secretion. 5.2% ± 1.4% (mean ± SD) of the dose was excreted as the trans-sulfoxide metabolite in the urine. Lamivudine is excreted in human breast milk and into the milk of lactating rats.

Pregnancy & Breastfeeding use

Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Lactation: Efavirenz may pass through breast milk and cause serious harm to the baby. It should not be used during lactation.

There is no adequate and well-controlled study in pregnant women. Lamivudine should be used during pregnancy only if the potential benefits outweigh the risks. Although it is not known if lamivudine is excreted in human milk, there is the potential for adverse effects from lamivudine in nursing infants. Mothers should be instructed not to breast feed if they are receiving lamivudine.

Contraindication

Hypersensitivity. Severe hepatic impairment. Lactation. Concomitant admin with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, ergot alkaloids, St John’s wort.

Lamivudine is contraindicated in patients hypersensitive to any of the components of the product.

Special Warning

Paediatric use: Efavirenz has not been studied in pediatric patients below 3 years of age or who weigh less than 10 kg.

Women taking hormone-based birth control: Women should not rely only on hormone-based birth control, such as pills, injections, or implants, because Efavirenz may make these contraceptives ineffective.

It is recommended that doses of Lamivudine should be adjusted in accordance with renal function. Dosage adjustment of Lamivudine in accordance with creatinine clearance is as follows:

CrCl 50 ml/min: 100 mg once daily
CrCl 30-49 ml/min: 100 mg first dose, then 50 mg once daily
CrCl 15-29 ml/min: 100 mg first dose, then 25 mg once daily
CrCl 5-14 ml/min: 35 mg first dose, then 15 mg once daily
CrCl <5 ml/min: 35 mg first dose, then 10 mg once daily

Use in children: Safety and efficacy of lamivudine for the treatment of chronic hepatitis B in children have not been established.