Lamivudine-Tenofovir DF

Lamivudine-Tenofovir DF is a combination medication used in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg.

• Lamivudine-Tenofovir DF is available under the following different brand names: Cimduo, Temixys

Common side effects of Lamivudine-Tenofovir DF include:

• headache, pain
• depression
• diarrhea
• rash
• fever
• abdominal pain
• back pain
• weakness
• nausea
• vomiting
• indigestion
• changes in the distribution of body fat
• joint or muscle pain
• insomnia
• dizziness
• numbness and tingling of extremities
• anxiety
• pneumonia

Serious side effects of Lamivudine-Tenofovir DF include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• new or worsening bone pain
• muscle weakness
• pain in the arms, hands, legs, or feet
• swelling around the midsection
• little or no urination
• swelling in your feet or ankles
• tiredness
• shortness of breath
• loss of appetite
• upper stomach pain (that may spread to the back)
• nausea
• vomiting
• dark urine
• clay-colored stools
• yellowing of the skin or eyes (jaundice)
• fever
• night sweats
• swollen glands
• cold sores
• cough
• wheezing
• diarrhea
• weight loss
• trouble speaking or swallowing
• problems with balance or eye movement
• weakness or prickly feeling
• swelling in the neck or throat (enlarged thyroid)
• menstrual changes
• impotence

Rare side effects of Lamivudine-Tenofovir DF include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 300 mg/300 mg

HIV Infection

Adult and pediatric dosage

• 1 tablet (lamivudine 300 mg/tenofovir 300 mg) orally once a day in combination with other antiretroviral therapy (ARTs)

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Lamivudine-Tenofovir DF has severe interactions with the following drug:
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • emtricitabine
• Lamivudine-Tenofovir DF has serious interactions with the following drugs:
  • betibeglogene autotemcel
  • cabotegravir
  • elivaldogene autotemcel
  • sorbitol
  • tafenoquine
  • trilaciclib
• Lamivudine-Tenofovir DF has moderate interactions with at least 25 other drugs
• Lamivudine-Tenofovir DF has minor interactions with the following drugs:
  • isavuconazonium sulfate
  • sulfamethoxazole
  • zidovudine

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Documented hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to any components contained in the formulation

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Lamivudine-Tenofovir DF?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lamivudine-Tenofovir DF?”

Cautions

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with the use of nucleoside analogs and other ARTs; suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity
• Clinical trials in HIV-infected subjects demonstrated regimens containing only 3 NRTIs are generally less effective than triple drug regimens containing 2 NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor or an HIV-1 protease inhibitor; early virological failure and high rates of resistance substitutions reported; use triple NRTI regimens with caution; carefully monitor patients on a therapy utilizing a triple nucleoside-only regimen and consider for treatment modification
• Not approved for chronic hepatitis B virus (HBV) infection and safety and efficacy not established in patients coinfected with HBV and HIV-1; if treatment with Epivir-HBV, tenofovir DF, or a tenofovir AF-containing product is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, the rapid emergence of HIV-1 resistance is likely to result because of subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment 
• Immune reconstitution syndrome is reported in HIV-infected patients treated with combination ART; during the initial phase of combination ART, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), tuberculosis), and further evaluation and treatment may be necessary
• Autoimmune disorders (Grave disease, polymyositis, and Guillain-Barré syndrome) are reported to occur in the immune reconstitution setting; however, time to onset varies and can occur many months after initiation of treatment
• In HIV-infected patients, redistribution/accumulation of body fat (e.g., central obesity, dorsocervical fat enlargement [buffalo hump], peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance) observed in patients receiving combination ART
• In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, Lamivudine should be used with caution
• Bone effects of tenofovir
  • In clinical trials, tenofovir DF was associated with slightly greater decreases in bone mineral density and increases in biochemical markers of bone metabolism
  • Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, reported
  • Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients
  • Effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults and pediatric subjects 2 years and older are unknown
  • Long-term effect of the lower spine and total body BMD on skeletal growth in pediatric patients, and in particular, effects of long-duration exposure in younger children unknown
  • Consider assessment of BMD for adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss; if bone abnormalities are suspected obtain appropriate consultation
• New onset or worsening renal impairment
  • Renal impairment (eg, acute renal failure, Fanconi syndrome) reported with the use of tenofovir DF
  • Before initiation and during therapy, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients; in patients with chronic kidney disease, also assess serum phosphorus
  • Cases of acute renal failure after initiation of high-dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDs) were reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir DF; some patients required hospitalization and renal replacement therapy
• Drug interactions overview
  • Tenofovir DF decreases AUC and minimal plasma concentrations of atazanavir; do not administer tenofovir DF with atazanavir without ritonavir; coadministration with drug combinations (.eg, lopinavir/ritonavir, atazanavir, and ritonavir, darunavir, and ritonavir) may increase tenofovir concentrations; monitor for tenofovir-associated adverse reactions; discontinue treatment in patients who develop tenofovir-associated adverse reactions
  • Since tenofovir is primarily eliminated by the kidneys, coadministration of Lamivudine-Tenofovir DF with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir and/or increase the concentrations of other renally eliminated drugs; avoid Lamivudine-Tenofovir DF with concurrent or recent use of a nephrotoxic agent (. eg, high-dose or multiple NSAIDs); consider alternatives to NSAIDs, if needed, in patients at risk for renal dysfunction
  • Lamivudine is predominantly eliminated in the urine by active organic cationic secretion; coadministration with drugs eliminated via an organic cationic transport system (. eg, trimethoprim) may interact with lamivudine
  • Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures; when possible, avoid the use of sorbitol-containing medicines with lamivudine
  • Hepatic decompensation, some fatal, reported in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy and interferon and ribavirin-based regimens; monitor for treatment-associated toxicities; discontinue therapy, as medically appropriate, and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both
• Hepatitis C antiviral agents
  • Coadministration of tenofovir DF with sofosbuvir/velpatasvir or ledipasvir/sofosbuvir has been shown to increase tenofovir exposure; monitor for adverse reactions associated with tenofovir DF
  • In patients receiving Lamivudine-Tenofovir DF concomitantly with ledipasvir/sofosbuvir with an HIV-1 protease inhibitor/ritonavir or an HIV-1 protease inhibitor/cobicistat combination, consider an alternative
  • HCV or antiretroviral therapy, the safety of increased tenofovir concentrations in this setting is not established; if coadministration is necessary, monitor for adverse reactions associated with tenofovir

Pregnancy and Lactation

• An ART pregnancy registry has been established (1-800-258-4263); prospective pregnancy data from the Antiviral Pregnancy Registry (APR) is not sufficient to adequately assess the risk of birth defects or miscarriage
• Lamivudine produced embryonic toxicity in rabbits at a dose that produced similar human exposures as the recommended clinical dose; the relevance of animal findings to human pregnancy registry data is not known; there are no adequate and well-controlled studies with tenofovir DF in pregnant women; tenofovir DF should be used during pregnancy only if needed
• Lactation
  • The CDC recommend that HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection
  • Lamivudine is excreted into human milk
  • Samples of breast milk obtained from five HIV-1-infected mothers in the first postpartum week show that tenofovir is excreted in human milk at low levels; the impact of this exposure in breastfed infants is unknown and the effects of tenofovir DF on milk production is unknown
  • Owing to the potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed