Usage
- Lamivudine + Stavudine is prescribed, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in patients weighing 60 kg or more and 12 years of age or older.
- Pharmacological Classification: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
- Mechanism of Action: Both lamivudine and stavudine are nucleoside analogs that inhibit HIV-1 reverse transcriptase by competing with natural nucleosides for incorporation into viral DNA. This results in chain termination, preventing further viral DNA synthesis.
Alternate Names
- This combination is often referred to as a component of Highly Active Antiretroviral Therapy (HAART).
- Brand Names: A specific brand name for the fixed-dose combination of lamivudine and stavudine was not found in the provided sources. However, both medications are available individually under various brand names (e.g. Epivir for lamivudine, Zerit for stavudine) and in fixed dose combinations with other drugs.
How It Works
- Pharmacodynamics: Both lamivudine and stavudine act intracellularly as their active triphosphate forms to inhibit HIV-1 reverse transcriptase, leading to a decrease in viral replication.
- Pharmacokinetics:
- Absorption: Both drugs are orally absorbed.
- Metabolism: Lamivudine is minimally metabolized and primarily excreted unchanged in the urine. Stavudine undergoes intracellular phosphorylation to its active form. Limited hepatic metabolism occurs for stavudine.
- Elimination: Primarily renal excretion for both drugs.
- Mode of Action: Intracellularly, both lamivudine and stavudine are phosphorylated to their active triphosphate forms. These active metabolites compete with natural substrates and incorporate into the viral DNA, causing chain termination and inhibiting HIV-1 reverse transcriptase.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Inhibition of HIV-1 reverse transcriptase enzyme.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- One fixed-dose combination tablet (containing specific amounts of lamivudine and stavudine, not found in the provided source) twice daily for patients weighing 60kg or more. This fixed-dose combination is specifically indicated for patients 12 years and older. The available sources do not mention specific brand names for the combination product.
- Administer on an empty stomach.
Children:
- The fixed-dose combination of lamivudine and stavudine is not recommended for children weighing less than 60 kg or younger than 12 years old, as dose adjustments within the fixed combination are not possible. Individual lamivudine and stavudine formulations with adaptable dosing may be necessary in younger children.
- Consult individual drug information for lamivudine and stavudine for specific pediatric dosing guidelines.
Special Cases:
- Elderly Patients: Exercise caution due to age-related decline in renal function. Closely monitor for peripheral neuropathy.
- Patients with Renal Impairment: Dose reduction is recommended in patients with creatinine clearance less than 50 mL/min. The fixed-dose combination tablet is not recommended due to inability to adjust individual drug doses. Use individual lamivudine and stavudine formulations.
- Patients with Hepatic Dysfunction: No dose adjustment of lamivudine is required. No specific guidance on stavudine dosage adjustment for hepatic impairment was found in the provided sources. Exercise caution with decompensated liver disease. Monitor liver function.
- Patients with Comorbid Conditions: Caution is advised in patients with a history of pancreatitis or peripheral neuropathy.
Clinical Use Cases
The provided sources did not specify dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- The fixed-dose combination tablet of lamivudine and stavudine is contraindicated for patients requiring dose adjustments. Individual lamivudine and stavudine formulations should be used. Dosage adjustments may be necessary based on renal function, hepatic function, and other patient-specific factors. Consult specific drug literature for dose adjustments.
Side Effects
Common Side Effects
- Headache, fatigue, nausea, diarrhea, nasal symptoms, abdominal pain, insomnia, dizziness, stuffy nose.
Rare but Serious Side Effects
- Lactic acidosis, severe hepatomegaly with steatosis, pancreatitis, peripheral neuropathy, blood or bone marrow problems (fever, chills, sore throat, pale skin, unusual tiredness or weakness), skin rash, changes in body fat distribution (lipoatrophy), depression, mood changes, easy bruising/bleeding, skin/nail color changes.
Long-Term Effects
- Lipoatrophy (loss of body fat), peripheral neuropathy.
Adverse Drug Reactions (ADR)
- Lactic acidosis, severe hepatomegaly with steatosis, severe skin reactions (rash), pancreatitis.
Contraindications
- Hypersensitivity to lamivudine or stavudine.
- Abnormally low neutrophil counts or hemoglobin levels (for zidovudine, which may apply by extension to other NRTIs).
- Severe liver impairment.
- Active pancreatitis.
- Advanced peripheral neuropathy.
Drug Interactions
- Zalcitabine: Co-administration is not recommended due to intracellular phosphorylation inhibition.
- Trimethoprim/Sulfamethoxazole (TMP/SMX): May increase lamivudine exposure.
- Sorbitol: May decrease lamivudine serum concentration.
- Zidovudine: No clinically significant interaction (when used in the fixed-dose combination).
- Didanosine: No clinically significant interaction (with stavudine).
- Nelfinavir: No clinically significant interaction (with stavudine).
- Other potentially nephrotoxic or myelosuppressive drugs: Monitor for toxicity.
Pregnancy and Breastfeeding
- Pregnancy: Not recommended unless the benefit clearly outweighs the risk. Limited data available regarding the combination of lamivudine and stavudine in pregnancy. Consult specialist guidance.
- Breastfeeding: Not recommended. Both lamivudine and stavudine are excreted in breast milk. Potential for adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) that cause DNA chain termination.
- Side Effects: Headache, fatigue, nausea, diarrhea, lactic acidosis, pancreatitis, peripheral neuropathy, lipoatrophy.
- Contraindications: Hypersensitivity, severe liver disease, active pancreatitis, advanced peripheral neuropathy.
- Drug Interactions: Zalcitabine, TMP/SMX, sorbitol.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Fixed-dose combination taken twice daily (specific dosages not provided).
- Monitoring Parameters: HIV-1 viral load, CD4 cell count, renal function, liver function, complete blood count, signs of pancreatitis and peripheral neuropathy.
Popular Combinations
- The fixed-dose combination of lamivudine and stavudine is intended to be used in combination with other antiretroviral agents as part of HAART. Specific drug combinations are determined by individual patient factors and current treatment guidelines.
Precautions
- General Precautions: Monitor for lactic acidosis, pancreatitis, and peripheral neuropathy. Conduct baseline and periodic liver and renal function tests, as well as complete blood counts.
- Specific Populations: Refer to the sections on dosing and pregnancy/breastfeeding.
- Lifestyle Considerations: Alcohol may increase the risk of pancreatitis and peripheral neuropathy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lamivudine + Stavudine?
A: The recommended dosage is one fixed-dose combination tablet twice daily for patients weighing at least 60 kg and 12 years or older. Specific dosages were not found in the available sources. Please consult the most recent treatment guidelines.
Q2: What are the common side effects of Lamivudine + Stavudine?
A: Common side effects include headache, fatigue, nausea, diarrhea, and nasal symptoms.
Q3: Who should not take Lamivudine + Stavudine?
A: Patients with hypersensitivity to either drug, severe liver disease, active pancreatitis, or advanced peripheral neuropathy should not take this combination.
Q4: Can Lamivudine + Stavudine be used in pregnant women?
A: It is generally not recommended unless the potential benefit outweighs the risk. Consult specialist guidance.
Q5: How does Lamivudine + Stavudine work?
A: They inhibit HIV-1 reverse transcriptase by incorporating into viral DNA and causing chain termination.
Q6: What are the serious side effects of Lamivudine + Stavudine?
A: Serious side effects include lactic acidosis, pancreatitis, peripheral neuropathy, and lipoatrophy.
Q7: Are there any drug interactions I should be aware of?
A: Yes, avoid co-administration with zalcitabine. Monitor for interactions with TMP/SMX and sorbitol.
Q8: Can this fixed-dose combination be used in children?
A: It is not recommended for children weighing less than 60 kg or younger than 12 years old, as dose adjustments within the fixed combination are not possible.
Q9: What should I monitor in patients taking this combination?
A: Monitor HIV viral load, CD4 counts, renal function, hepatic function, and complete blood count. Watch for signs of lactic acidosis, pancreatitis and peripheral neuropathy.
Q10: What is the elimination route for these drugs?
A: Primarily renal excretion.
