Efavirenz

Efavirenz (Efavirenz) is an antiretroviral drug used in the treatment of human immunodeficiency virus (HIV) infection. It belongs to a class of drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs) and is an important part of antiretroviral therapy.

The drug inhibits the activity of the reverse transcriptase enzyme, which is necessary for the HIV virus to reproduce. It binds to this enzyme and inhibits its work, which prevents the conversion of viral RNA into DNA and the subsequent integration of viral DNA into the host genome. This helps to slow down the multiplication of the virus in the body and reduce its concentration in the blood, leading to better health outcomes for the patient and a reduced risk of transmission to others.

Efavirenz is often included in combination antiretroviral drugs such as Atripla, which also contains tenofovir and emtricitabine. Combined use of multiple drugs can help reduce the risk of the virus developing drug resistance and increase the effectiveness of treatment.

Indications Efavirenza

Efavirenz is used as part of combination antiretroviral therapy for the treatment of infection caused by human immunodeficiency virus type 1 (HIV-1) in adults, adolescents and children aged 3 months and older who have confirmed HIV infection and require antiretroviral treatment.

The main indications for the use of efavirenz:

1. Treatment of HIV-1 infection: As part of combination treatment with other antiretroviral drugs to reduce viral load and support immune function.
2. Preventing the progression of HIV infection: Reducing the risk of acquired immunodeficiency syndrome (AIDS) and other HIV-associated diseases.

Efavirenz is usually administered as part of antiretroviral therapy, which includes protease inhibitors, nucleoside and non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, and other classes of antiretroviral drugs depending on the individual patient's needs and clinical condition.

It is important to note that efavirenz is not a drug to completely cure HIV infection. It is used to control the virus and maintain the quality of life of patients. Before and during treatment, patients should be under close medical supervision to monitor the effectiveness of therapy and possible side effects.

Release form

Efavirenz is available as oral tablets. Efavirenz tablets usually have standardized dosages that are preferably taken whole, with water, and with certain doctor's recommendations, may be taken with meals.

Pharmacodynamics

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination antiretroviral therapy for the treatment of infection caused by human immunodeficiency virus (HIV). The mechanism of action of efavirenz involves specific inhibition of the action of the HIV reverse transcriptase enzyme, which plays a key role in viral replication.

Mechanism of Action:

1. Reverse transcriptase inhibition: Efavirenz directly binds to HIV reverse transcriptase, but unlike nucleoside reverse transcriptase inhibitors, it does not require phosphorylation for activation. Efavirenz changes the conformation of the active center of the enzyme, which leads to a decrease in its activity and consequently blocks the process of transcription of viral RNA into DNA. This prevents the integration of viral DNA into the host genome and subsequent viral replication.
2. Preventing viral replication: By inhibiting reverse transcriptase, efavirenz effectively stops HIV replication in infected cells, resulting in a reduced viral load in the body.
3. Reducing viral load: Reducing the activity and amount of virus in the blood helps improve the body's immune response and reduces the risk of acquired immunodeficiency syndrome (AIDS) and other HIV-associated diseases.

Efavirenz is highly selective to HIV-1 reverse transcriptase with negligible effect on human DNA polymerases, which makes it effective and relatively safe for the treatment of HIV infection as part of combination antiretroviral therapy. However, like any antiretroviral drug, efavirenz may cause side effects and requires careful monitoring of the patient's condition during treatment.

Pharmacokinetics

The pharmacokinetics of efavirenz is characterized by several key aspects that determine its absorption, distribution, metabolism and excretion:

Absorption:

• Efavirenz is rapidly absorbed after oral administration, with maximum plasma concentrations (Cmax) reached approximately 3-5 hours after administration.
• The bioavailability of efavirenz is increased when taken with food, especially fatty foods, which may increase its plasma concentration.

Distribution:

• Efavirenz is well distributed in tissues, with a volume of distribution greater than total body water, indicating good tissue penetration.
• The drug binds to plasma proteins approximately 99.5-99.75%, mainly albumin and acidic alpha1-glycoprotein.

Metabolism:

• Efavirenz is extensively metabolized in the liver with the participation of cytochrome P450, mainly by CYP2B6 isoforms and to a lesser extent by CYP3A4.
• Metabolism results in the formation of several metabolites that are less active than unchanged efavirenz.

Withdrawal:

• Efavirenz and its metabolites are eliminated from the body mainly with urine and feces.
• The average elimination half-life of efavirenz is 40 to 55 hours, which allows it to be used once daily.

These pharmacokinetic characteristics make efavirenz convenient to use, as a single dose per day is sufficient to maintain effective therapy. However, individual differences in metabolism, especially those associated with genetic variations in CYP2B6, may affect the blood concentration of efavirenz in different patients, which requires careful attention to dosing and treatment monitoring.

Dosing and administration

The standard dosage is 600 mg once a day. Efavirenz should be taken on an empty stomach, as ingestion of a high-fat meal may significantly increase the drug concentration in the blood, potentially leading to increased side effects.

Use Efavirenza during pregnancy

The use of efavirenz during pregnancy for women living with HIV should be considered in light of the potential risks and benefits. In a study to examine the effects of the drug in HIV-positive pregnant and lactating women, participants received efavirenz at a dosage of 600 mg daily as part of combination antiretroviral therapy. This study aims to evaluate the safety and efficacy of efavirenz in the context of preventing mother-to-child transmission of HIV and maintaining maternal and child health during breastfeeding. [1]

It is important to note that the decision to use efavirenz or any other HIV drug during pregnancy should be based on a careful weighing of potential risks and benefits, taking into account the individual clinical situation. It is recommended to discuss this issue with your physician, who can provide up-to-date information and recommendations based on the latest research and clinical guidelines.

In general, current recommendations suggest that efavirenz can be used throughout pregnancy, including the first trimester. This is based on data indicating that women who successfully suppress the virus with regimens including efavirenz and become pregnant should continue taking the drug during pregnancy. However, as with any medication, it is important to have a detailed discussion with the treating physician to assess all potential risks and benefits to the mother and baby.

In the context of HIV and pregnancy, starting treatment early, even if you feel well and have a high CD4 cell count, is considered the best way to maintain your health. The World Health Organization recommends that all pregnant and lactating women living with HIV start treatment as soon as possible and continue it throughout their lives to protect their health and reduce the risk of perinatal HIV transmission.

Contraindications

Despite its effectiveness, Efavirenz has a number of contraindications that are important to consider before starting treatment.

The main contraindications to the use of Efavirenz include:

1. Allergy or hypersensitivity to Efavirenz or any of the drug components.
2. Serious liver problems such as acute hepatitis or decompensated cirrhosis, as Efavirenz may worsen liver function.
3. Co-administration with certain medicines that may interact with Efavirenz, causing serious side effects or reducing the effectiveness of treatment. These drugs include, for example, certain antifungals, antiarrhythmic drugs, statins, certain antibiotics and others.
4. Pregnancy, especially in the first trimester, as there is a risk of harm to the developing fetus. Women of childbearing age taking Efavirenz are advised to use reliable contraceptive methods during treatment and for some time after its termination.

It is also important to consider that Efavirenz may cause some psychiatric and neurological side effects such as dizziness, sleep disturbances, insomnia, strange dreams, seizures or depression. Although these conditions are not always contraindications to taking the drug, they require careful monitoring and possibly treatment adjustments depending on the patient's individual response.

Side effects Efavirenza

Efavirenz side effects may vary in severity and frequency of occurrence. Some of the most common side effects include:

Central Nervous System:

• Dizziness, headaches, insomnia, drowsiness, unusual dreams or nightmares. These symptoms most often occur during the initial phase of treatment and may gradually decrease as therapy continues.
• Increased fatigue and impaired concentration.
• In rare cases, serious neurological reactions such as depression, aggression, hallucinations, psychosis and suicidal thoughts may occur.

Cutaneous reactions:

• A rash that can range from mild to severe, including Stevens-Johnson syndrome and toxic epidermal necrolysis. The rash usually occurs during the first weeks of treatment.

Metabolic disorders:

• There may be an increase in blood cholesterol and triglyceride levels.
• Changes in measures of liver function.

Other possible side effects:

• Sleep disorders, including insomnia or excessive sleepiness.
• Nausea and vomiting, especially during the initial phase of treatment.
• It is possible to develop immune reconstitution syndrome, a condition in which improvement in the immune system leads to inflammation and worsening of pre-existing infections or diseases.

It is important to note that the listed side effects do not occur in all patients taking efavirenz and their severity may vary significantly.

Overdose

An overdose of Efavirenz can lead to serious side effects because it is a powerful antiretroviral drug used in the treatment of HIV infection. Symptoms of Efavirenz overdose may include, but are not limited to, the following:

1. Neurological symptoms: dizziness, headache, insomnia, drowsiness, seizures or unusual dreams. These are some of the most common side effects of Efavirenz, which may be exacerbated by overdose.
2. Psychiatric symptoms: acute psychosis, hallucinations, paranoia, severe depression, aggression or suicidal ideation. These conditions require immediate attention from medical professionals.
3. Gastrointestinal symptoms: nausea, vomiting, diarrhea, abdominal pain. Although these symptoms may be less severe, they can contribute to dehydration and further deterioration of health.
4. Increasedliver toxicity: increased liver enzyme levels, jaundice, deterioration of liver function.

If an overdose is suspected, medical attention should be sought immediately. Treatment of Efavirenz overdose may include symptomatic treatment and supportive therapy, such as maintenance of vital organ function, monitoring of neurological and mental status, and measures to prevent absorption of the drug from the gastrointestinal tract, if possible and acceptable in terms of time after overdose.

There is no specific antidote for the treatment of Efavirenz overdose, so it is important to strictly follow the recommended dosages and consult your doctor regularly during treatment with this drug.

Interactions with other drugs

Efavirenz may interact with different medicines, which may alter their effectiveness or increase the risk of side effects. Here are some important interactions to watch out for:

Interactions that reduce the effectiveness of Efavirenz:

• Antituberculosis drugs (e.g., rifampicin) may decrease the blood concentration of efavirenz, which will require a dose adjustment.
• Epilepsy medications (e.g., phenytoin, phenobarbital, carbamazepine) may also decrease the effectiveness of efavirenz.

Interactions that increase the risk of Efavirenz side effects:

• Proton pump inhibitors and H2-receptor blockers: may increase the blood concentration of efavirenz, increasing its side effects.
• Drugs metabolized via CYP3A4: Because efavirenz is an inducer and inhibitor of CYP3A4, it can affect the metabolism and concentration of other drugs such as statins, opioid analgesics, anticoagulants, and many others.

Interactions requiring dosage adjustment:

• Antiretroviral drugs: Some antiretroviral drugs may require dosage adjustment when co-administered with efavirenz due to mutual effects on metabolism.
• Oral contraceptives and hormonal preparations: Efavirenz may reduce their effectiveness, which requires additional contraceptive methods to prevent unwanted pregnancy.

Special Cautions:

• Alcohol and recreational drugs: Combination with alcohol or recreational drugs may increase the side effects of efavirenz, especially those related to the central nervous system.

Before starting efavirenz, it is important to tell your doctor about all medications you are taking, including over-the-counter medications, vitamins, and supplements, to avoid potentially dangerous interactions.

Storage conditions

The storage conditions for Efavirenz are important to maintain its effectiveness and safety. Although specific details may vary slightly depending on the manufacturer and the form of release, it is generally recommended to store Efavirenz in a dry place protected from light at room temperature. The drug should be kept away from children and should not be exposed to high temperatures or humidity. It is also important to check the expiration date of the drug and not to use it after the specified period.