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Therapeutic Classification: antiretrovirals

Pharmacologic Classification: nucleoside reverse transcriptase inhibitors

• HIV — 1 infection (in combination with other antiretroviral agents).

• Lamivudine: After intracellular conversion to its active form (lamivudine-5-triphosphate), inhibits viral DNA synthesis by inhibiting the enzyme HIV reverse transcriptase.
• Tenofovir: Phosphorylated intracellularly where it inhibits HIV reverse transcriptase resulting in disruption of DNA synthesis.

• Slowed progression of HIV infection and decreased occurrence of sequelae.

Lamivudine

Absorption: Well absorbed after oral administration (86% in adults, 66% in infants and children).

Distribution: Distributes into the extravascular space; some penetration into CSF.

Metabolism/Excretion: Mostly excreted unchanged in urine; <5% metabolized by the liver.

Half-life: 5–7 hr.

Tenofovir Disoproxil Fumarate

Absorption: Tenofovir disoproxil fumarate is a prodrug, which is split into tenofovir, the active component; absorption enhanced by food.

Distribution: Distributes into the extravascular space.

Metabolism/Excretion: 70–80% excreted unchanged in urine by glomerular filtration and active tubular secretion.

Half-life: 17 hr.

(plasma concentrations)

†When taken with food.

Contraindicated in:

• Hypersensitivity
• Co-infection with hepatitis B virus (HBV) (hepatitis may recur after discontinuation of lamivudine or tenofovir) (lamivudine dose not appropriate for patients co-infected with HBV)
• CCr <50 mL/min
• Concurrent or recent use of nephrotoxic medications
• Concurrent use with ribavirin and/or interferon alfa (↑ risk of hepatic decompensation)
• Lactation: Breastfeeding not recommended for mothers with HIV.

Use Cautiously in:

• History of pathologic fractures/osteoporosis/bone loss
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Children <35 kg (safety and effectiveness not established).
• Geri: Choose dose carefully, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function

Exercise Extreme Caution in:

• Pedi: Children with a history of or significant risk factors for pancreatitis (use only if no alternative).

Derm: rash, urticaria.

F and E: LACTIC ACIDOSIS.

GI: diarrhea, ↑ liver enzymes, abdominal pain, dyspepsia, HEPATOMEGALY WITH STEATOSIS, nausea, PANCREATITIS (↑ IN PEDIATRIC PATIENTS), vomiting.

GU: ACUTE RENAL FAILURE/FANCONI SYNDROME, hematuria.

Hemat: neutropenia.

Metab: ↑creatine kinase, hypercholesterolemia, fat redistribution.

MS: ↓bone mineral density, arthralgia, muscle weakness, myalgia, osteomalacia.

Neuro: depression, headache, anxiety, dizziness, insomnia, peripheral neuropathy.

Misc: , , fever, immune reconstitution syndrome.

Drug-Drug:

• Nephrotoxic drugs, including acyclovir, aminoglycosides, cidofovir, ganciclovir, NSAIDs, valacyclovir, or valgancyclovir may ↑ risk of nephrotoxicity; avoid recent or concurrent use.
• May ↑ risk of hepatic decompensation with ribavirin or interferon alfa; avoid concurrent use.
• Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir may ↑ tenofovir levels.
• Trimethoprim/sulfamethoxazole may ↑ lamivudine levels.
• Medications containing sorbitol may ↓ lamivudine levels.

• PO (Adults and Children 35 kg): 1 tablet once daily.

• Tablets: lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg;

• Monitor for change in severity of HIV symptoms and for symptoms of opportunistic infection before and during therapy.
• Monitor bone mineral density in patients who have a history of pathologic bone fracture or are at risk for osteoporosis or bone loss. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy.

• Monitor viral load and CD4 count before and routinely during therapy to determine response.
  • Test for hepatitis B before starting therapy. Monitor liver function tests and hepatitis B virus levels during and following therapy. If therapy is discontinued, may cause severe exacerbation of hepatitis B. May cause ↑ AST, ALT, alkaline phosphatase, creatine kinase, amylase, and triglyceride concentrations. Lactic acidosis may occur with hepatotoxicity causing hepatic steatosis; may be fatal, especially in women.
  • Assess serum creatinine, serum phosphorus, CCr, urine glucose, and urine protein before starting and periodically during therapy. Calculate CCr prior to and periodically during therapy and when clinically indicated. In patients at risk of renal dysfunction, assess CCr, serum phosphorus, urine glucose, and urine protein prior to and periodically during therapy. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy.
  • Monitor serum phosphate periodically during therapy in patients at risk for renal impairment. May cause hypophosphatemia in patients with renal impairment.
  • May cause hyperglycemia and glucosuria.

• PO: Administer once daily with or without food.

• Instruct patient on the importance of taking lamivudine/tenofovir as directed, even if feeling better. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Discontinuing therapy may lead to severe exacerbations. Advise patient to make sure they have enough medication to not run out; the virus may increase and may become harder to treat. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Caution patient not to share or trade this medication with others. Advise patient to read Patient Teaching before starting and with each Rx refill in case of changes.
• Caution patient to avoid crowds and persons with known infections.
• Inform patient that lamivudine/tenofovir does not cure AIDS and may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and avoid sharing needles or donating blood to prevent spreading HIV to others.
• Advise patient to notify health care professional immediately if symptoms of lactic acidosis (tired; nausea; vomiting; unusual or unexpected stomach discomfort; trouble breathing; feeling cold, dizzy, lightheaded; fast or irregular heartbeat; weakness), pancreatitis, or signs of immune reconstitution syndrome (signs and symptoms of an infection) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Inform patient that changes in body fat distribution (increased fat in upper back and neck, breast, and trunk, and loss of fat from legs, arms, and face) may occur, but may not be related to drug therapy.
• Rep: Advise females or reproductive potential taking oral contraceptives to use a nonhormonal method of birth control during lamivudine/tenofovir therapy. If pregnancy is suspected notify health care professional promptly. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise female patient to avoid breastfeeding during therapy.
• Emphasize the importance of regular exams to monitor for side effects.

• Decreased incidence of opportunistic infection and slowed progression of HIV infection.

Cimduo

NDC Code^*

• 49502- Mylan Specialty L.P.
  • 49502-450- CIMDUO
    • 49502-450-93- 1 BOTTLE, PLASTIC in 1 CARTON (49502-450-93) > 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

• 72606- CELLTRION USA, INC.
  • 72606-002- TEMIXYS
    • 72606-002-01- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (72606-002-01)