Usage
- Medical Conditions: Lamivudine + Tenofovir disoproxil fumarate is prescribed for the treatment of HIV-1 infection in adults and children weighing at least 35 kg. It is also used for pre-exposure prophylaxis (PrEP) to reduce the risk of HIV-1 infection in adults and adolescents weighing at least 35 kg. It is part of antiretroviral therapy (ART) and must be used in combination with other antiretroviral agents. It is sometimes used to treat chronic Hepatitis B.
- Pharmacological Classification: Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Antiretroviral combination.
- Mechanism of Action: Both lamivudine and tenofovir disoproxil fumarate interfere with the virus’s ability to replicate its genetic material (RNA) into DNA. This inhibits viral replication and reduces the viral load in the body.
Alternate Names
- While the generic name is Lamivudine + Tenofovir disoproxil fumarate, it’s often referred to simply as Lamivudine/Tenofovir.
- Brand Names: Cimduo, Temixys. Other brand names are available when combined with other medications (Symfi, Symfi Lo, etc.)
How It Works
- Pharmacodynamics: Both drugs are phosphorylated to active metabolites inside the cell. These metabolites then act as competitive substrates and inhibitors of HIV-1 reverse transcriptase, resulting in premature chain termination of DNA synthesis.
- Pharmacokinetics:
- Absorption: Tenofovir disoproxil fumarate is a prodrug that is rapidly converted to tenofovir after oral administration. Lamivudine is well-absorbed.
- Metabolism: Tenofovir is minimally metabolized. Lamivudine is also minimally metabolized.
- Elimination: Tenofovir is primarily excreted renally. Lamivudine is primarily eliminated unchanged in urine.
- Mode of Action: These drugs inhibit HIV-1 reverse transcriptase by acting as competitive chain terminators during DNA synthesis.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Competitive chain termination of HIV-1 reverse transcriptase activity.
- Elimination Pathways: Renal excretion is the primary pathway for both drugs.
Dosage
Standard Dosage
Adults:
- One tablet (containing 300 mg lamivudine and 300 mg tenofovir disoproxil fumarate) once daily, taken orally with or without food.
Children:
- For HIV treatment, one tablet daily for children weighing 35 kg or more. Use is not indicated in children weighing less than 35 kg.
- For PrEP, not used in children weighing less than 35 kg due to limited data on safety and efficacy.
- Pediatric safety considerations: Careful monitoring of renal function is necessary in children.
Special Cases:
- Elderly Patients: No specific dose adjustments, but close monitoring of renal function is recommended.
- Patients with Renal Impairment: Not recommended for patients with creatinine clearance (CrCl) less than 50 mL/min.
- Patients with Hepatic Dysfunction: No specific dose adjustments, but close monitoring of hepatic function is recommended.
- Patients with Comorbid Conditions: Dose adjustments may be necessary based on specific comorbid conditions.
Clinical Use Cases
This medication is specifically indicated for the treatment and prevention of HIV-1 infection. Dosing for other clinical use cases is not available.
Dosage Adjustments
Dose adjustments are primarily based on renal function. Hepatic impairment generally does not require dose adjustments.
Side Effects
Common Side Effects:
- Headache
- Pain
- Diarrhea
- Rash
- Depression
- Changes in the shape or location of body fat (lipodystrophy)
Rare but Serious Side Effects:
- Lactic acidosis
- Severe hepatomegaly with steatosis
- Renal impairment
- Bone problems (osteoporosis, bone pain, fractures)
- Pancreatitis
- Immune reconstitution syndrome (worsening of pre-existing infections)
- New or worsening bone pain
- Muscle weakness
- Peripheral neuropathy
- Swelling around the midsection
Long-Term Effects:
- Renal dysfunction
- Bone loss
- Changes in body fat distribution
Adverse Drug Reactions (ADR):
- Lactic acidosis
- Hepatotoxicity
- Severe acute exacerbations of hepatitis B (in patients co-infected with HBV)
- Renal failure
- Pancreatitis
Contraindications
- Hypersensitivity to lamivudine or tenofovir disoproxil fumarate
- Severe renal impairment (CrCl < 50 mL/min)
Drug Interactions
- Other nephrotoxic drugs (NSAIDs, aminoglycosides)
- Atazanavir (requires ritonavir co-administration)
- Other antiretroviral drugs (protease inhibitors, NNRTIs)
- Sorbitol (avoid chronic co-administration)
- Orlistat
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not assigned. Can be used when benefits outweigh risks. A pregnancy exposure registry is available.
- Fetal Risks: Limited human data suggest the risk of birth defects is low.
- Breastfeeding: Breastfeeding is not recommended due to the potential for HIV transmission.
Drug Profile Summary
- Mechanism of Action: Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs).
- Side Effects: Headache, pain, diarrhea, rash, depression, lipodystrophy, lactic acidosis, hepatotoxicity, renal impairment.
- Contraindications: Hypersensitivity, severe renal impairment.
- Drug Interactions: Nephrotoxic drugs, atazanavir, other antiretrovirals, sorbitol.
- Pregnancy & Breastfeeding: Use in pregnancy only if clearly needed; breastfeeding not recommended.
- Dosage: One tablet (300 mg/300 mg) orally once daily.
- Monitoring Parameters: Renal function (creatinine, CrCl, urine glucose, urine protein), liver function tests, HBV serology (if applicable), HIV viral load, CD4 count.
Popular Combinations
- Often combined with other antiretroviral agents, such as dolutegravir, efavirenz, or rilpivirine, as part of combination ART.
Precautions
- General Precautions: Renal and hepatic function monitoring. HBV testing prior to initiation.
- Specific Populations: Monitor renal function closely in elderly patients. Not recommended in severe renal impairment. Caution in patients with hepatic impairment.
- Lifestyle Considerations: Avoid chronic use of sorbitol. Safe sex practices are essential, even when using PrEP or ART.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lamivudine + Tenofovir disoproxil fumarate?
A: One tablet (300mg lamivudine/300mg tenofovir disoproxil fumarate) orally once daily.
Q2: What are the most common side effects?
A: Headache, pain, diarrhea, rash, depression, and changes in body fat distribution.
Q3: Is this medication safe for pregnant women?
A: It should be used during pregnancy only when the potential benefits outweigh the potential risks to the fetus.
Q4: Can this medication be used in patients with renal impairment?
A: It is not recommended for patients with CrCl less than 50 mL/min.
Q5: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and return to your regular dosing schedule. Do not double the dose.
Q6: Does this medicine cure HIV?
A: No. This medicine reduces the viral load and slows down the progression of the disease but does not cure HIV.
Q7: Can I drink alcohol while taking this medicine?
A: Excessive alcohol consumption should be avoided as it may increase the risk of liver problems and pancreatitis.
Q8: What if I am co-infected with HIV and Hepatitis B?
A: Close monitoring of liver function is crucial. If appropriate, anti-hepatitis B treatment should be initiated. Severe exacerbations of hepatitis B have been reported after discontinuation of lamivudine/tenofovir.
Q9: Can I take antacids with this medication?
A: Some antacids may decrease the absorption of tenofovir. If you must take an antacid, space it a few hours before or after taking Lamivudine/Tenofovir. Consult with a pharmacist about possible drug interactions.
Q10: Can I use this medication for PEP (post-exposure prophylaxis)?
A: No, this particular combination tablet is not typically used for PEP. Other ART regimens are used in PEP. Consult other sources for information on PEP.
