Temixys

Last updated on RxList: 6/21/2021
Temixys Side Effects Center

What Is Temixys?

Temixys (lamivudine and tenofovir disoproxil fumarate) is a combination of two nucleoside reverse transcriptase inhibitors indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg.

What Are Side Effects for Temixys?

Common side effects of Temixys include

Dosage for Temixys

The recommended dose of Temixys in adults and pediatric patients weighing at least 35 kg is one tablet once daily with or without food.

Prior to initiation and during treatment with Temixys, patients should be tested for hepatitis B virus infection, and estimated creatinine clearance, urine glucose, and urine protein should be obtained.

What Drugs, Substances, or Supplements Interact with Temixys?

Temixys may interact with:

Tell your doctor all medications and supplements you use.

Temixys During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Temixys it is unknown how it would affect a fetus. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Temixys during pregnancy. Because breast milk can transmit HIV, breastfeeding while using Temixys is not recommended.

Additional Information

Our Temixys (lamivudine and tenofovir disoproxil fumarate) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Temixys Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • new or worsening bone pain;
  • muscle weakness;
  • pain in your arms, hands, legs, or feet;
  • swelling around your midsection;
  • kidney problems--little or no urination, swelling in your feet or ankles, feeling tired or short of breath; or
  • signs of liver or pancreas problems--loss of appetite, upper stomach pain (that may spread to your back), nausea or vomiting, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Lamivudine and tenofovir affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:

  • signs of a new infection--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; or
  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.

Common side effects may include:

  • headache;
  • pain;
  • diarrhea;
  • rash;
  • depression; or
  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Temixys (Lamivudine and Tenofovir Disoproxil Fumarate Tablets)

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Temixys Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in other sections of the labeling:

  • Exacerbations of hepatitis B [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
  • New onset or worsening renal impairment [see WARNINGS AND PRECAUTIONS]
  • Immune reconstitution syndrome [see WARNINGS AND PRECAUTIONS]
  • Bone Loss and Mineralization Defects [see WARNINGS AND PRECAUTIONS]
  • Lactic acidosis and severe hepatomegaly with steatosis [see WARNINGS AND PRECAUTIONS]
  • Hepatic decompensation in patient co-infected with HIV-1 and hepatitis C [see WARNINGS AND PRECAUTIONS]
  • Pancreatitis [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Lamivudine And Tenofovir Disoproxil Fumarate

Clinical Trials In Treatment-Naive HIV-1 Infected Adult Subjects

In Trial 903, 600 antiretroviral-naive subjects received TDF (N=299) or stavudine (d4T) (N=301) administered in combination with lamivudine (3TC) and efavirenz (EFV) for 144 weeks. The most common adverse reactions were mild to moderate gastrointestinal events and dizziness. Mild adverse reactions (Grade 1) were common with a similar incidence in both arms, and included dizziness, diarrhea, and nausea. Table 1 provides the treatment-emergent adverse reactions (Grade 2-4) occurring in greater than or equal to 5% of subjects treated in any treatment group.

Table 1: Selected Adverse Reactionsa (Grades 2-4) Reported in ≥5% in Any Treatment Group in Trial 903 (0-144 Weeks)

TDF + 3TC + EFV
N=299
d4T + 3TC + EFV
N=301
Rash eventb 18% 12%
Headache 14% 17%
Pain 13% 12%
Diarrhea 11% 13%
Depression 11% 10%
Back pain 9% 8%
Nausea 8% 9%
Fever 8% 7%
Abdominal pain 7% 12%
Asthenia 6% 7%
Anxiety 6% 6%
Vomiting 5% 9%
Insomnia 5% 8%
Arthralgia 5% 7%
Pneumonia 5% 5%
Dyspepsia 4% 5%
Dizziness 3% 6%
Myalgia 3% 5%
Lipodystrophyc 1% 8%
Peripheral neuropathyd 1% 5%
a Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug.
b Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash.
cLipodystrophy represents a variety of investigator-described adverse events not a protocol-defined syndrome.
d Peripheral neuropathy includes peripheral neuritis and neuropathy.

Laboratory Abnormalities

Table 2 provides a list of laboratory abnormalities (Grades 3-4) observed in Trial 903. With the exception of fasting cholesterol and fasting triglyceride elevations that were more common in the d4T group (40% and 9%) compared with tenofovir disoproxil fumarate group (19% and 1%), respectively, laboratory abnormalities observed in this trial occurred with similar frequency in the tenofovir disoproxil fumarate and d4T treatment arms.

Table 2: Grades 3-4 Laboratory Abnormalities Reported in ≥1% of tenofovir disoproxil fumarate-treated subjects in Trial 903 (0-144 Weeks)

TDF + 3TC + EFV
N=299
d4T + 3TC + EFV
N=301
Any ≥ Grade 3 Laboratory Abnormality 36% 42%
Fasting Cholesterol (>240 mg/dL) 19% 40%
Creatine Kinase (M: >990 U/L; F: >845 U/L) 12% 12%
Serum Amylase (>175 U/L) 9% 8%
AST (M: >180 U/L; F: >170 U/L) 5% 7%
ALT (M: >215 U/L; F: >170 U/L) 4% 5%
Hematuria (>100 RBC/HPF) 7% 7%
Neutrophils (<750/mm³) 3% 1%
Fasting Triglycerides (>750 mg/dL) 1% 9%

Pancreatitis

Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral nucleoside-experiences pediatric subjects receiving 3TC alone or in combination with other antiretroviral agents [see WARNINGS AND PRECAUTIONS].

Changes In Bone Mineral Density

In HIV-1 infected adult subjects in Trial 903, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in subjects receiving TDF + 3TC + EFV (-2.2% ± 3.9) compared with subjects receiving d4T + 3TC + EFV (-1.0% ± 4.6) through 144 weeks. Changes in BMD at the hip were similar between the two treatment groups (-2.8% ± 3.5 in the TDF group vs. -2.4% ± 4.5 in the d4T group). In both groups, the majority of the reduction in BMD occurred in the first 24-48 weeks of the trial and this reduction was sustained through Week 144. Twenty-eight percent of TDF-treated subjects vs. 21% of the d4T-treated subjects lost at least 5% of BMD at the spine or 7% of BMD at the hip. Clinically relevant fractures (excluding fingers and toes) were reported in 4 subjects in the TDF group and 6 subjects in the d4T group. In addition, there were significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C telopeptide, and urinary N telopeptide) and higher serum parathyroid hormone levels and 1,25 Vitamin D levels in the TDF group relative to the d4T group; however, except for bone-specific alkaline phosphatase, these changes resulted in values that remained within the normal range [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during post-approval use for each of the individual components of TEMIXYS. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to 3TC and TDF.

Lamivudine

Body as a Whole: Redistribution/accumulation of body fat.

Endocrine and Metabolic: Hyperglycemia.

General: Weakness.

Hemic and Lymphatic: Anemia (including pure red cell aplasia and severe anemias progressing on therapy).

Hepatic and Pancreatic: Lactic acidosis and hepatic steatosis [see WARNINGS AND PRECAUTIONS], posttreatment exacerbations of hepatitis B [see WARNINGS AND PRECAUTIONS].

Hypersensitivity: Anaphylaxis, urticaria.

Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.

Skin: Alopecia, pruritus.

Tenofovir Disoproxil Fumarate

Immune System Disorders: allergic reaction, including angioedema.

Metabolism and Nutrition Disorders: lactic acidosis, hypokalemia, hypophosphatemia.

Respiratory, Thoracic, and Mediastinal Disorders: dyspnea.

Gastrointestinal Disorders: pancreatitis, increased amylase, abdominal pain.

Hepatobiliary Disorders: hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT).

Skin and Subcutaneous Tissue Disorders: rash.

Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy.

Renal and Urinary Disorders: acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria.

General Disorders and Administration Site Conditions: asthenia.

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

DRUG INTERACTIONS

Drugs Affecting Renal Function

Tenofovir, a component of TEMIXYS, is primarily eliminated by the kidneys [see CLINICAL PHARMACOLOGY]. Coadministration of TEMIXYS with drugs that are eliminated by active tubular secretion may increase serum concentrations of tenofovir and/or coadministered drug. Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see WARNINGS AND PRECAUTIONS]. Drugs that decrease renal function may increase concentrations of tenofovir.

Do not administer TEMIXYS with HEPSERA (adefovir dipivoxil).

Established And Significant Interactions

Table 3 provides a listing of established or clinically significant drug interactions. The drug interactions described are based on studies conducted with TDF [see CLINICAL PHARMACOLOGY].

Table 3: Established and Significanta Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Trials

Concomitant Drug Class: Drug Name Effect on Concentrationb Clinical Comment
NRTI: didanosine ↑ didanosine Patients receiving TDF, a component of TEMIXYS, and didanosine should be monitored closely for didanosine-associated adverse reactions. Discontinue didanosine in patients who develop didanosine-associated adverse reactions. Higher didanosine concentrations could potentiate didanosine-associated adverse reactions, including pancreatitis, and neuropathy. Suppression of CD4+ cell counts has been observed in patients receiving TDF with didanosine 400 mg daily.
In patients weighing greater than 60 kg, reduce the didanosine dose to 250 mg when it is coadministered with TDF. In patients weighing less than 60 kg, reduce the didanosine dose to 200 mg when it is coadministered with TDF. When coadministered, tenofovir disoproxil fumarate and Videx® - EC may be taken under fasted conditions or with a light meal (less than 400 kcal, 20% fat).
HIV-1 Protease Inhibitors: Atazanavir
lopinavir/ritonavir
atazanavir/ritonavir
darunavir/ritonavir
↓ atazanavir
↑ tenofovir
When coadministered with TEMIXYS, atazanavir 300 mg should be given with ritonavir 100 mg.
Monitor patients receiving TEMIXYS concomitantly with lopinavir/ritonavir, ritonavir-boosted atazanavir, or ritonavir-boosted darunavir for TDF-associated adverse reactions. Discontinue TEMIXYS in patients who develop TDF-associated adverse reactions.
Hepatitis C Antiviral Agents: sofosbuvir/velpatasvir
sofosbuvir/velpatasvir/ voxilaprevir
ledipasvir/sofosbuvir
↑ tenofovir Monitor patients receiving TEMIXYS concomitantly with EPCLUSA® (sofosbuvir/velpatasvir) for adverse reactions associated with TDF.
Monitor patients receiving TEMIXYS concomitantly with HARVONI® (ledipasvir/sofosbuvir) without an HIV-1 protease inhibitor/ritonavir or an HIV-1 protease inhibitor/cobicistat combination for adverse reactions associated with TDF. In patients receiving TEMIXYS concomitantly with HARVONI® and an HIV-1 protease inhibitor/ritonavir or an HIV-1 protease inhibitor/cobicistat combination, consider an alternative HCV or antiretroviral therapy, as the safety of increased tenofovir concentrations in this setting has not been established. If coadministration is necessary, monitor for adverse reactions associated with TDF.
a. This table is not all inclusive.
b. ↑=Increase, ↓=Decrease

Drugs Inhibiting Organic Cation Transporters

3TC, a component of TEMIXYS, is predominantly eliminated in the urine by active organic cationic secretion. The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim) [see CLINICAL PHARMACOLOGY]. No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of 3TC.

Sorbitol

Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Temixys (Lamivudine and Tenofovir Disoproxil Fumarate Tablets)

© Temixys Patient Information is supplied by Cerner Multum, Inc. and Temixys Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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