Lamivudine + Nevirapine + Tenofovir disoproxil fumarate

Usage

• This fixed-dose combination medication is prescribed for the treatment of Human Immunodeficiency Virus-1 (HIV-1) infection in adults and adolescents. It’s crucial that the patient is virologically suppressed (HIV-1 RNA < 50 copies/mL) and currently on a stable antiretroviral therapy regimen with no history of treatment failure. Also, no known resistance should exist to any of the drug’s individual components.
• Pharmacological Classification: Antiretroviral, specifically a combination of two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - Lamivudine and Tenofovir disoproxil fumarate - and one Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) - Nevirapine.
• Mechanism of Action: Lamivudine and Tenofovir interfere with the virus’s ability to replicate its genetic material by inhibiting reverse transcriptase, a viral enzyme. Nevirapine also targets reverse transcriptase, but at a different binding site, further hampering viral replication. This combination approach helps suppress the viral load and strengthens the immune system.

Alternate Names

• There is no internationally recognized non-proprietary name for this specific three-drug combination. However, the individual components are frequently found in various fixed-dose combinations.
• Brand Names: There are no brand names explicitly listed for this exact three-drug combination, although the individual drugs are marketed under several brand names.

How It Works

• Pharmacodynamics: The combination exerts synergistic antiviral effects by inhibiting HIV-1 reverse transcriptase, preventing the conversion of viral RNA into DNA. This hinders viral replication and reduces the viral load, leading to improved immune function.
• Pharmacokinetics:
  • Absorption: Tenofovir disoproxil fumarate is a prodrug that gets converted to the active form, tenofovir diphosphate, inside cells. Lamivudine and Nevirapine are readily absorbed after oral administration.
  • Metabolism: Lamivudine and Nevirapine are primarily metabolized in the liver via various pathways. Tenofovir disoproxil fumarate is metabolized to tenofovir, and undergoes further intracellular phosphorylation to the active diphosphate form.
  • Elimination: Lamivudine and Tenofovir are primarily eliminated through renal excretion. Nevirapine is extensively metabolized by the liver and excreted in the urine, mostly as metabolites.
• Mode of Action: These drugs act as competitive inhibitors of HIV-1 reverse transcriptase, disrupting the formation of proviral DNA.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: The drugs target viral reverse transcriptase. There is no known significant interaction with human receptors or neurotransmitters.
• Elimination Pathways: Primarily renal excretion for Lamivudine and Tenofovir, and hepatic metabolism followed by renal excretion for Nevirapine.

Dosage

Because this specific combination of Lamivudine, Nevirapine, and Tenofovir disoproxil fumarate is not available as a single, fixed-dose combination tablet, specific dosage recommendations are not applicable. For accurate information, consult the dosage guidelines for the particular fixed-dose combination product prescribed.

Standard Dosage

Not applicable to this specific combination.

Clinical Use Cases

Not applicable to this specific combination.

Dosage Adjustments

Not applicable to this specific combination.

Side Effects

Common Side Effects

• Nausea, vomiting, diarrhea
• Headache, dizziness, fatigue
• Rash, skin reactions
• Sleep disturbances

Rare but Serious Side Effects

• Lactic acidosis
• Hepatic steatosis and hepatic failure
• Severe skin reactions
• Pancreatitis
• Renal dysfunction
• Peripheral neuropathy

Long-Term Effects

• Osteoporosis and decreased bone mineral density
• Renal impairment
• Metabolic abnormalities (dyslipidemia, insulin resistance)

Adverse Drug Reactions (ADR)

• Lactic acidosis
• Stevens-Johnson Syndrome, toxic epidermal necrolysis
• Drug-induced liver injury

Contraindications

• Hypersensitivity to any component of the combination
• Severe hepatic impairment
• Coadministration with strong CYP3A4 inducers

Drug Interactions

• Other antiretroviral medications: Coadministration with other NNRTIs is generally not recommended due to potential for overlapping toxicity and drug interactions.
• Rifampicin, Rifabutin: Strong CYP3A4 inducers, should be avoided or used with caution.
• Certain anticonvulsants (e.g., Phenytoin, Carbamazepine): Can reduce drug levels.
• St. John’s Wort: Can reduce drug levels.
• Antacids: Can decrease the absorption of Tenofovir.

Pregnancy and Breastfeeding

• The combination is generally not recommended during pregnancy or breastfeeding unless the potential benefit outweighs the risk. For detailed guidance, refer to the specific fixed-dose combination containing these drugs.

Drug Profile Summary

Refer to the information above for the mechanism of action, side effects, contraindications, drug interactions, pregnancy/breastfeeding information, and dosage.

Popular Combinations

This specific combination is not commonly used as a fixed-dose formulation. The components are found in different two or three drug combinations, consult available fixed-dose regimens for usage and dosing guidelines.

Precautions

• Monitor for hepatic and renal function
• Monitor bone mineral density
• Screen for hepatitis B and C coinfection
• Counsel patients about potential side effects and drug interactions

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Lamivudine + Nevirapine + Tenofovir disoproxil fumarate?

A: This specific three-drug combination is not typically prescribed as a single pill. Dosage will depend on the specific fixed-dose combination prescribed and should be determined by a physician experienced in treating HIV infection.

Q2: Can this combination be used in pregnant women?

A: It’s generally not recommended unless potential benefits outweigh the risks. Consultation with a specialist is essential. It’s important to follow expert guidelines for managing HIV infection in pregnant women.

Q3: What are the common side effects patients should be aware of?

A: Common side effects include nausea, vomiting, diarrhea, headache, fatigue, rash, and sleep disturbances.

Q4: Are there any serious side effects associated with this combination?

A: Yes, rare but serious side effects include lactic acidosis, severe skin reactions, hepatotoxicity, pancreatitis, and renal dysfunction.

Q5: What monitoring is recommended while on this combination?

A: Regular monitoring of renal and hepatic function, as well as bone mineral density, is advisable. Periodic viral load monitoring is crucial for evaluating treatment efficacy.

Q6: What are the key drug interactions to consider?

A: Important interactions occur with other antiretrovirals, especially NNRTIs, and drugs metabolized by the CYP3A4 pathway such as rifampin and certain anticonvulsants.

Q7: Is there a risk of hepatitis B reactivation upon discontinuation?

A: Yes, particularly for those with chronic hepatitis B coinfection. Close monitoring and potential antiviral treatment for hepatitis B might be necessary.

Q8: Can this medication cure HIV?

A: No, this medication effectively manages HIV but does not eradicate it. It helps reduce viral load, improve immune function, and prevent opportunistic infections, requiring lifelong therapy.

Q9: Can HIV still be transmitted while taking this medication?

A: Although the medication significantly suppresses the viral load, there’s still a possibility of transmission, particularly if the viral load isn’t fully suppressed. Safe sex practices are always recommended.

Q10: How should this medication be taken?

A: Dosing and administration should be in accordance with the specific formulation prescribed by the physician. Generally, the medication should be taken orally once daily, with or without food, depending on the specific product.