Cimduo is a combination of Lamivudine (a cytosine analog) and Tenofovir disoproxil fumarate (nucleotide reverse transcriptase inhibitor) that is used in combination with other antiretroviral drugs for the treatment of patients with HIV-1 infections.

Cimduo (Lamivudine and Tenofovir disoproxil fumarate) Uses:

• HIV-1 infection:

  • It is indicated in the treatment of HIV-1 infection in combination with other antiretroviral agents in adult and pediatric patients weighing ≥35 kg.

Cimduo (Lamivudine and Tenofovir disoproxil fumarate) Dose in Adults:

Cimduo (Lamivudine and Tenofovir disoproxil fumarate) Dose in the treatment of HIV-infection:

• Oral: One tablet once daily in combination with other antiretroviral agents

Cimduo (Lamivudine and Tenofovir disoproxil fumarate) Dose in Children:

Note: Use in combination with other antiretroviral agents.

Cimduo (Lamivudine and Tenofovir disoproxil fumarate) Dose in the treatment of HIV-1 infection:

• Children and Adolescents weighing <35 kg:

  • Not recommended; (its a fixed-dose combination)

• Children and Adolescents weighing ≥35 kg:

  • Oral: 1 tablet  a day

Cimduo (Lamivudine and Tenofovir disoproxil fumarate) Pregnancy Risk Category: C

• The Health and Human Services' (HHS) Perinatal HIV Guidelines recommends that lamivudine and tenofovir DF be considered as the preferred NRTI backbone to initiate treatment in pregnant antiretroviral-naive females.
• This combination is also preferred in pregnancy
  • Those who have received antiretroviral treatment (ART) previously but are now resuming their treatment
  • Patients who have poor tolerance to or poor virologic response and need to begin a new ART regimen
  • People who aren't yet pregnant, but are trying to conceive.
• If the combination is well tolerated, pregnant women may continue to take it if they are able to get pregnant.
• Guidelines also recommend lamivudine and tenofovir DFU as a dual NRTI backbone for HIV/HBV-coinfected pregnant women.

Use of tenofovir disoproxil fumarate and Lamivudine during lactation

• Breast milk contains tenofovir disoproxil fumarate and lamivudine
• For more information, refer to the individual monographs.

Dose in Kidney Disease:

• CrCl ≥50 mL/minute:
  • No dosage adjustment is necessary.
• CrCl <50 mL/minute:
  • Not recommended
• ESRD requiring hemodialysis:
  • Not recommended

Dose in Liver disease:

No dosage adjustments listed in the manufacturer's labelling.

Side effects of Cimduo (Lamivudine and Tenofovir disoproxil fumarate):

See individual agents.

Contraindications to Cimduo (Lamivudine and Tenofovir disoproxil fumarate):

• Hypersensitivity to lamivudine or tenofovir disoproxil fumarate.

Warnings and precautions

• Reduced bone mineral density

  • Clinical trials have shown that tenofovir DF is associated with decreased bone mineral density in HIV-1-infected adults, and an increase in bone metabolism markers.
  • Serum PTH and 1,25 vitamin D levels were also high.
  • We don't know the long-term effects of bone health and fracture risk in the future, as well as effects on skeletal growth in children and young patients.
  • According to pediatric clinical trials, it does not affect height (skeletal growth).
  • Monitoring: Bone density in adults, and children with a history or risk factors for osteoporosis or pathologic fractures.
  • Supplementation with calcium and vitamin D for all patients. Although its effects are not yet known, they may prove to be beneficial.
  • Expert evaluation in the event of suspected abnormalities

• Immune reconstitution syndrome:

  • Patients may develop immune reconstitution syndrome
  • An inflammatory response may occur to an indolent, residual opportunistic HIV infection, or activation of autoimmune diseases (eg, Graves, polymysitis, Guillain Barre syndrome) during initial HIV treatment.
  • If the patient has reconstitution syndrome, further evaluation and treatment may be necessary.

• Lactic acidosis/hepatomegaly:

  • Combining nucleoside analog with antiretroviral medications can lead to lactic acidosis or severe hepatomegaly and steatosis. Sometimes it can even be fatal.
  • Stop the drug if the patient develops lactic Acidosis (pronounced hepatotoxicity) (markedly increased transaminase level with or without hepatomegaly or steatosis).

• Osteomalacia, renal dysfunction

  • It can lead to osteomalacia and proximal renal tubulopathy.
  • There have been reports of bone pain, extremity pain and muscle pain.
  • Patients at high risk for renal dysfunction who have persistent bone and muscle symptoms should be evaluated for hypophosphatemia or osteomalacia.

• Toxicity in the renal system:

  • Tenofovir disoproxil fumarate can cause renal toxicity (acute kidney failure and/or Fanconi Syndrome).
  • It is best to avoid any concomitant or recent nephrotoxic drugs, including NSAIDs.
  • Concomitant use tenofovir disoproxil (high dose) and NSAIDs (multiple NSAIDs), in HIV-infected patients has led to acute renal failure.
  • You might consider alternatives to NSAIDs for such patients.
  • Monitoring: All patients should be monitored for the estimated CrCl, serum creatinine and urine glucose.
  • Patients with CKD have lower serum phosphorus.
  • The IDSA guidelines recommend:
    • Patients with a decrease in GFR (a GFR of >25% from baseline and to a level 60mL/minute/1.73m2) during treatment, especially in the presence of proximal tube dysfunction (euglycemic, increased urinary Phosphorus excretion, hypophosphatemia, and proteinuria)
    • Switch to an alternative antiretroviral treatment for HIV-infected people.

• Chronic Hepatitis B: [US-Boxed Warning]

  • Patients infected with HIV-1 and hepatitis B virus have reported severe acute exacerbations of their hepatitis B after discontinuing antiretroviral treatment.
  • A close monitoring of liver function with both laboratory and clinical follow-up is recommended for at least three months.
  • If necessary, anti-hepatitis-B therapy may be required in advanced liver disease or chronic cirrhosis.
  • All HIV-positive patients should be tested for HBV before starting treatment.

• Renal impairment

  • CrCl 50mL/minute on hemodialysis or CrCl >50mL/minute: contraindicated

Lamivudine and tenofovir disoproxil fumarate: Drug Interaction

Monitoring parameters:

• CD4 count
• HIV RNA plasma levels
• Serum creatinine, serum phosphorous levels in patients with CKD
• Urine R/E (urine glucose, urine protein) plus estimated creatinine clearance before starting the therapy and as clinically indicated during therapy
• Liver function tests (LFTs)
• Bone density: For patients with a history of bone fracture or at high risk for bone loss
• Hepatitis B virus (HBV) testing before starting antiretroviral therapy. Patients with HIV and HBV coinfection should be monitored for several months after discontinuation of therapy.

How to administer Cimduo (Lamivudine and Tenofovir disoproxil fumarate)?

Oral: Can be taken with or without food.

Mechanism of action of Cimduo (Lamivudine and Tenofovir disoproxil fumarate):

Lamivudine:

• It is a cytosine analogue that undergoes phosphorylation in the cell to its active 5’-triphosphate metabolism. It blocks HIV reverse transcriptase via viral genome chain termination.

Tenofovir disoproxil fumarate (DF):

• It is a nucleotide-reverse transcriptase inhibitor, (NRTI), and an analog of adenosine 5’ monophosphate
• Tenofovir DF undergoes hydrolysis first, then converts into tenofovir and is then phosphorylated back to its active form tenofovir phosphate.
• This active form interferes with HIV-dependent DNA polymerase, resulting in inhibition of viral reproduction.

See individual agents.

International Brand Names of Lamivudine and tenofovir disoproxil fumarate:

• Cimduo
• Temixys
• Duomune
• Lamihope T
• Mivuten
• Recovir-L
• Teladine
• Telavir
• Tenolam
• Tenvir-L

Lamivudine and tenofovir disoproxil fumarate Brand Names in Pakistan:

No Brands Available in Pakistan.