Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate Tablets 600mg/200mg/300mg

Indications

• HIV-1 infection
• HIV infection in combination with other antiretroviral drugs

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: 600 mg once daily, administered orally, preferably at bedtime to minimize CNS effects.

Mechanism of action

Efavirenz inhibits the activity of viral RNA-directed DNA polymerase, also known as reverse transcriptase. This inhibition interferes with the generation of DNA copies of viral RNA, which are necessary for producing new virions. The drug diffuses into the cell and binds to the reverse transcriptase enzyme, causing a conformational change that results in enzyme inhibition. This process is vital for preventing viral replication, although it does not eliminate HIV from the body.

Pharmacodynamics

As a non-nucleoside reverse transcriptase inhibitor, efavirenz exhibits virustatic properties, meaning it inhibits viral replication without directly killing the virus. Its pharmacodynamic effects are influenced by its intracellular conversion to an active triphosphorylated form. This conversion is variable, depending on the cell type, but ultimately leads to effective inhibition of HIV replication. Efavirenz is often used in conjunction with other antiretrovirals as part of a comprehensive treatment approach for HIV.

Pharmacokinetics

Efavirenz is well-absorbed when administered orally, and its bioavailability is affected by food intake. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes (CYP2B6), leading to the formation of active metabolites. The drug has a long half-life, allowing for once-daily dosing. It is important to monitor liver function due to potential hepatotoxicity, especially in patients with existing liver conditions. The pharmacokinetics may be altered by drug interactions, necessitating dose adjustments in certain situations.

Contra-indications

• Severe hypersensitivity to efavirenz or any component of the formulation
• Acute porphyrias
• History of psychiatric disorders
• History of seizures
• Severe hepatic impairment

Adverse effects

• Rash
• Dizziness
• Nausea
• Vomiting
• Abdominal pain
• Asthenia
• Diarrhoea
• Sleep disorders
• CNS effects (e.g., confusion, hallucinations)
• Fatigue
• Mood alterations
• Suicidal behavior
• Hepatocellular injury
• Seizures
• Stevens-Johnson syndrome

Interactions

• Posaconazole: severe decrease in exposure
• Antimalarials: severe decrease in exposure
• Atovaquone: severe decrease in exposure
• Benzodiazepines: severe interaction affecting effects
• Midazolam: severe interaction affecting effects
• Voriconazole: moderate decrease in exposure
• Caspofungin: moderate decrease in concentration
• Ciclosporin: moderate decrease in concentration
• Coumarins: moderate interaction affecting concentration
• Opioids: moderate decrease in exposure

Precautions

• Caution in patients with history of psychiatric disorders or seizures
• Caution in elderly patients
• Monitor liver function if receiving other hepatotoxic drugs
• Caution in patients with chronic hepatitis B or C
• Driving and skilled tasks may be affected due to CNS effects

Pregnancy

Reports of neural tube defects when used in the first trimester. Manufacturer advises avoiding use during pregnancy.

Breast-feeding

Limited information available; caution is advised.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• 600 mg capsules
• 600 mg tablets

Indications

• HIV infection

Dosage

Children: Child 4 months–17 years (body-weight up to 33 kg): 6 mg/kg once daily. Child 4 months–17 years (body-weight 33 kg and above): 240 mg once daily.

Adults: 200 mg once daily by mouth using capsules or 240 mg once daily by mouth using oral solution.

Mechanism of action

Emtricitabine is a cytidine analog that, when phosphorylated to emtricitabine 5'-triphosphate, competes with deoxycytidine 5'-triphosphate for HIV-1 reverse transcriptase. It incorporates itself into the viral DNA during replication, leading to chain termination. This prevents the incorporation of additional nucleotides and inhibits the transcription of viral RNA into DNA, thereby preventing viral replication.

Pharmacodynamics

Emtricitabine acts by competing with natural substrates of HIV-1 reverse transcriptase, leading to the termination of viral DNA synthesis. It has a long duration of action, allowing for once-daily dosing. Clinicians should monitor for potential side effects, including lactic acidosis and hepatomegaly with steatosis, which can occur with nucleoside analogs.

Pharmacokinetics

Emtricitabine is absorbed well following oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It has a long half-life, allowing for its once-daily administration. Emtricitabine is primarily excreted through the kidneys, and dosage adjustments may be necessary in patients with renal impairment. It is metabolized minimally by the liver.

Contra-indications

• Severe hepatic impairment
• Severe renal impairment (creatinine clearance <30 mL/min)

Adverse effects

• Decreased appetite
• Asthenia
• Constipation
• Diarrhoea
• Dizziness
• Electrolyte imbalance
• Flatulence
• Gastrointestinal discomfort
• Headache
• Abnormal dreams
• Dyspepsia
• Hyperbilirubinaemia
• Hyperglycaemia
• Hypersensitivity reactions
• Hypertriglyceridaemia
• Neutropenia
• Pain
• Rash
• Pustular skin reactions
• Sleep disorders
• Angioedema (uncommon)

Interactions

• Cobicistat and elvitegravir may impact emtricitabine efficacy
• Potential for increased risk of treatment failure in pregnancy when used with elvitegravir
• Monitor for changes in drug levels when co-administered with other antiretrovirals

Precautions

• Caution in patients with hepatic impairment due to increased risk of side effects
• Monitor renal function regularly, particularly in those with existing renal impairment
• Patients should be advised on the risks of lactic acidosis and hepatomegaly with steatosis

Pregnancy

Not recommended for initiation during pregnancy due to risk of treatment failure and maternal-to-child transmission of HIV-1. Women who become pregnant during therapy should be switched to an alternative regimen.

Breast-feeding

Emtricitabine is excreted in human breast milk, caution is advised when administering to breastfeeding mothers.

Storage

Store in the original container, protected from moisture, and keep out of reach of children.

Formulations

• 200 mg capsules
• 240 mg oral solution

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Used as a disintegrant in tablet formulations
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

Store in a cool, dry place, away from moisture and heat.

Formulations

• Powder
• Granules

Indications

• HIV-1 infection
• Chronic hepatitis B virus (HBV) infection

Dosage

Children: Refer to the BNF for

Adults: Refer to the relevant clinical guidelines or BNF for the appropriate dosing recommendations.

Mechanism of action

Disoproxil is converted intracellularly to its active form, tenofovir diphosphate. This active metabolite competes with natural deoxyadenosine triphosphate (dATP) for incorporation into viral DNA by the viral reverse transcriptase enzyme. Once incorporated, it leads to chain termination, thereby inhibiting viral replication. Additionally, tenofovir diphosphate interferes with the activity of HIV reverse transcriptase and HBV polymerase, further contributing to its antiviral effects.

Pharmacodynamics

Disoproxil exhibits a dose-dependent decrease in HIV-1 viral load and improves CD4 cell counts in patients. Its antiviral activity is primarily against HIV-1 and HBV, with a mechanism that does not exhibit cross-resistance with other classes of antiretroviral drugs. The drug has a long half-life, allowing for once-daily dosing, which improves adherence in patients. It is effective in both naïve and treatment-experienced patients.

Pharmacokinetics

Disoproxil is absorbed following oral administration; its bioavailability is approximately 25% when taken without food. The drug is extensively distributed in the body, with a volume of distribution of about 1.3 L/kg. It undergoes renal clearance, with about 70% of the drug eliminated unchanged in the urine. The elimination half-life of disoproxil is around 17 hours, allowing for once-daily dosing. It is not significantly metabolized by the liver, which reduces the risk of drug-drug interactions associated with hepatic metabolism.

Contra-indications

• Hypersensitivity to disoproxil or any component of the formulation
• Severe renal impairment

Adverse effects

• Nausea
• Diarrhea
• Headache
• Fatigue
• Renal toxicity
• Liver function abnormalities
• Bone mineral density loss
• Lactic acidosis

Interactions

• Potential interactions with nephrotoxic drugs
• May interact with other antiviral agents
• Can affect the metabolism of drugs that are substrates of CYP450 enzymes

Precautions

• Monitor renal function regularly during therapy
• Assess bone mineral density before and during treatment
• Use with caution in patients with a history of pancreatitis
• Evaluate liver function before initiation and during treatment

Pregnancy

Disoproxil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on human use.

Breast-feeding

Disoproxil is excreted in breast milk. A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral tablets
• Oral solution

Indications

• Used as an excipient in pharmaceutical formulations
• Improves solubility and stability of active ingredients
• Facilitates drug absorption

Dosage

Children: Refer to specific product guidelines as hydroxypropyl is typically used as an excipient and not dosed independently.

Adults: Refer to specific product guidelines as hydroxypropyl is typically used as an excipient and not dosed independently.

Mechanism of action

Hydroxypropyl functions primarily as a solubilizing agent, which aids in the dissolution of poorly soluble drugs. It interacts with water and other solvents to improve the dispersion of pharmaceutical compounds, thereby enhancing their bioavailability. Hydroxypropyl may also facilitate the permeability of drug molecules through biological membranes, contributing to their overall efficacy.

Pharmacodynamics

The pharmacodynamics of hydroxypropyl relate to its role in improving the physicochemical properties of drug formulations. By increasing solubility and stability, hydroxypropyl can enhance the absorption of drugs administered via various routes, including oral and topical. Its non-toxic nature allows for safe incorporation into formulations, making it suitable for a wide range of applications.

Pharmacokinetics

The pharmacokinetics of hydroxypropyl have not been extensively studied as it primarily acts as an excipient rather than an active pharmaceutical ingredient. When used in formulations, it is typically not absorbed into systemic circulation in significant amounts, thereby minimizing potential systemic effects. Hydroxypropyl is generally regarded as safe when used in appropriate amounts in drug formulations.

Pregnancy

Hydroxypropyl is not classified for use during pregnancy, and its safety has not been established. Caution is advised.

Breast-feeding

There is limited information on the excretion of hydroxypropyl in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Indications

• Cleansing agent in topical formulations
• Emulsifying agent in cosmetic products
• Foaming agent in shampoos and body washes

Dosage

Children: Refer to specific product formulations for appropriate concentrations and application methods.

Adults: Refer to specific product formulations for appropriate concentrations and application methods.

Mechanism of action

Lauryl sulfate functions as an anionic surfactant. It reduces the surface tension between different substances, allowing for better spreading and wetting. In the context of cleansing, it facilitates the removal of dirt and oils from the skin and hair by emulsifying these substances, thus making them easier to rinse away with water.

Pharmacodynamics

As a surfactant, lauryl sulfate displays properties that can disrupt cellular membranes and alter permeability. This mechanism is beneficial in enhancing the penetration of other therapeutic agents in topical formulations. However, its irritant potential on skin and mucous membranes should be noted, as it can lead to dryness and irritation with prolonged exposure.

Pharmacokinetics

Lauryl sulfate is primarily applied topically and is not intended for systemic absorption. When used in formulations, it acts locally at the site of application. Its absorption through the skin is minimal, and any systemic exposure is limited. Metabolism and excretion pathways are not well-defined for topical applications, as it is largely washed away after use.

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Unknown whether lauryl is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

Store in a cool, dry place away from direct sunlight and moisture.

Indications

• Tablet coating
• Granule coating
• Improvement of drug stability
• Taste masking
• Aesthetic enhancement of pharmaceuticals

Dosage

Children: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Adults: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Mechanism of action

Opadry functions primarily as a coating polymer that adheres to the surface of tablets or granules, creating a protective layer. This layer can control the release of the active ingredient and protect it from environmental factors such as moisture and light. The specific composition of Opadry can vary, but it typically includes film-forming agents, plasticizers, and colorants that work together to achieve the desired coating characteristics.

Pharmacodynamics

The pharmacodynamics of Opadry is largely focused on its physical and chemical properties rather than specific biological interactions. The coating alters the dissolution characteristics of the drug, potentially leading to modified release profiles. This can enhance drug bioavailability or control the release rate of the active ingredient, thereby impacting the therapeutic effect.

Pharmacokinetics

As a coating agent, Opadry itself is not absorbed into the systemic circulation and does not have pharmacokinetic properties related to absorption, distribution, metabolism, or excretion of an active pharmaceutical ingredient. Its impact on pharmacokinetics is indirect, as it affects how the active drug is released and absorbed in the gastrointestinal tract.

Pregnancy

Opadry is a film-coating agent, and specific studies on its effects during pregnancy are not well-documented. Generally, it is advisable to use medications cautiously during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited data are available regarding the safety of Opadry during breastfeeding. It is recommended to consult a healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• Opadry OY - a coating system for oral solid dosage forms
• Opadry II - a polymer-based coating system for tablet and capsule applications

Mechanism of action

The exact mechanism of action for Pink is not detailed in the provided information. However, compounds with similar structures often function as antagonists or inhibitors at certain receptors or enzymes, which modulates physiological processes.

Pharmacodynamics

Pharmacodynamics details for Pink are not specified. Typically, the pharmacodynamics of similar compounds involve interactions with neurotransmitter systems, influencing both central and peripheral nervous system functions. This can lead to varying therapeutic effects depending on the target receptors.

Pharmacokinetics

The pharmacokinetics of Pink, including absorption, distribution, metabolism, and excretion, are not explicitly stated. However, compounds of this nature generally exhibit moderate to high oral bioavailability, with metabolism primarily occurring in the liver, followed by renal excretion of metabolites.

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• HIV infection
• Chronic hepatitis B

Dosage

Children: Refer to BNF for Children for specific pediatric dosing information.

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Once tenofovir is activated by bi-phosphorylation, it functions as an antiviral acyclic nucleoside phosphonate. It inhibits viral reverse transcriptase, exhibiting an inhibitory constant of approximately 0.022 micromolar. Tenofovir competes with deoxyadenosine 5'-triphosphate to generate new viral DNA, leading to chain termination and inhibition of viral replication. Its safety profile is maintained due to its low affinity for cellular DNA polymerases, including mitochondrial DNA polymerase gamma.

Pharmacodynamics

Tenofovir has demonstrated high efficacy in treatment-naive HIV patients, showing comparable effectiveness to efavirenz while exhibiting lower toxicity than some other antiretrovirals, such as stavudine. In patients with hepatitis B, tenofovir treatment has been associated with undetectable viral DNA levels after one year.

Pharmacokinetics

Tenofovir is absorbed after oral administration and is primarily eliminated by the kidneys. It has a half-life that allows for once-daily dosing and achieves therapeutic concentrations in plasma and tissues. The metabolism of tenofovir involves conversion to its active form, which is then incorporated into viral DNA, leading to its antiviral effects.

Contra-indications

• Hypersensitivity to tenofovir or any excipients in the formulation
• Severe renal impairment (CrCl < 30 mL/min) without appropriate dosage adjustment

Adverse effects

• Nausea
• Diarrhea
• Headache
• Fatigue
• Renal impairment
• Bone density loss
• Lactic acidosis

Interactions

• Antiepileptics (carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone) with tenofovir alafenamide: Severe (decreases exposure)
• Tipranavir with tenofovir alafenamide: Severe (decreases exposure)
• Rifamycins with tenofovir alafenamide: Severe (decreases exposure)
• St John’s Wort with tenofovir alafenamide: Severe (decreases exposure)
• Fostemsavir with tenofovir disoproxil: Moderate (increases exposure)
• Fostemsavir with tenofovir alafenamide: Moderate (increases exposure)
• Ciclosporin with tenofovir alafenamide: Unknown (increases exposure)
• Ciclosporin with tenofovir disoproxil: Unknown (increases exposure)
• Eltrombopag with tenofovir alafenamide: Unknown (increases exposure)
• Eltrombopag with tenofovir disoproxil: Unknown (increases exposure)

Precautions

• Monitor renal function regularly during treatment
• Use with caution in patients with a history of renal disease
• Consider bone density monitoring in patients on long-term therapy

Pregnancy

Tenofovir is categorized as a pregnancy category B drug. Animal studies have not shown any harm, but human data is limited. Weigh risks and benefits when prescribing during pregnancy.

Breast-feeding

Tenofovir is excreted in breast milk, but the amount is considered low. The benefits of breastfeeding should be considered against the potential risk of HIV transmission.

Storage

Store at room temperature (20-25°C) in a tightly closed container. Keep away from light and moisture.

Mechanism of action

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. Efavirenz diffuses into the cell where it binds adjacent to the active site of reverse transcriptase. This produces a conformational change in the enzyme that inhibits function.

Pharmacodynamics

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.

Mechanism of action

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. Emtricitabine, a synthetic nucleoside analog of cytosine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, epsilon and mitochondrial DNA polymerase gamma.

Pharmacodynamics

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.

Mechanism of action

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.

Pharmacodynamics

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.