lamivudine/tenofovir disoproxil fumarate

Contraindicated in:

Hypersensitivity;
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:

Chronic hepatitis B virus (HBV) infection (may exacerbate following discontinuation);
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 in older adults.

Exercise Extreme Caution in:

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

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, urticaria

F and E: LACTIC ACIDOSIS

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

GU: ACUTE RENAL FAILURE/FANCONI SYNDROME, hematuria

Hemat: neutropenia

Metab: ↑CK, 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

Interactions ⬆ ⬇

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 ↑ levels and risk of toxicity of tenofovir.
Trimethoprim/sulfamethoxazole may ↑ levels and risk of toxicity of lamivudine levels.
Medications containing sorbitol may ↓ levels and effectiveness of lamivudine.

Availability ⬆ ⬇

Tablets: lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥35 kg): One tablet once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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.

Therapeutic effects:

Slowed progression of HIV infection and decreased occurrence of sequelae.

Classifications ⬆ ⬇

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: nucleoside reverse transcriptase inhibitors

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
lamivudine (PO)	unknown	0.9 hr	12 hr
tenofovir (PO)	unknown	2 hr‡	24 hr

‡When taken with food.

Patient/Family Teaching ⬆ ⬇

Instruct patient on the importance of taking lamivudine/tenofovir as directed, even if feeling better. Do not take more than prescribed amount. Advise patient to make sure they have enough medication to not run out; the virus may ↑ 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.
Do not stop taking without consulting health care provider. Discontinuing therapy may lead to severe exacerbations. Inform patient of importance of HBV testing before starting antiretroviral therapy.
Caution patient to avoid crowds and persons with known infections.
Inform patient that lamivudine/tenofovir does not cure HIV and may ↓ 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 provider immediately if symptoms of lactic acidosis (tired; nausea; vomiting; unusual or unexpected stomach discomfort; trouble breathing; feeling cold, dizzy, or light-headed; 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Inform patient that changes in body fat distribution (↑ fat in upper back and neck, breast, and trunk; loss of fat from legs, arms, and face) may occur, but may not be related to drug therapy.
Rep: Advise women of reproductive potential to use a nonhormonal method of birth control during therapy. If pregnancy is suspected, notify health care provider promptly. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise women to avoid breastfeeding during therapy.
Emphasize the importance of regular exams to monitor for side effects.

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Indications ⬇

Contraind./Precautions ⬆ ⬇