What are the possible side effects of Tenvira?
Tenvira may cause serious side effects, including:
- See Important information.
- Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after starting your HIV-1 medicine.
- New or worse kidney problems, including kidney failure. Your healthcare provider should do blood and urine tests to check your kidneys before you start and during treatment. Your healthcare provider may tell you to stop treatment if you develop new or worse kidney problems.
- Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat.
- Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including Tenvira can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or if you start urinating more often during treatment.
- Changes in body fat can happen in people who take HIV-1 medicines. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.
- Increased bleeding for hemophiliacs. Some people with hemophilia have increased bleeding with protease inhibitors.
The most common side effects of Tenvira, include:
- diarrhea
- rash
- nausea
- fatigue
- headache
- stomach problems
- gas
These are not all of the possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Side effects of Tenvira in details
The following adverse reactions are discussed in other sections of the labeling:
- Severe acute exacerbations of hepatitis B
- Hepatotoxicity
- Severe skin reactions
- Immune reconstitution syndrome
- New onset or worsening renal impairment
- Lactic acidosis/severe hepatomegaly with steatosis
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.
Adverse Reactions in Adults with No Prior Antiretroviral Treatment History
The safety profile of Tenvira in HIV-1 infected adults with no prior antiretroviral treatment history is based on Week 48 data from the AMBER trial, a randomized, double-blind, active-controlled trial where a total of 362 subjects received Tenvira once daily and 363 subjects received a combination of PREZCOBIX® (fixed-dose combination of darunavir and cobicistat) and fixed-dose combination of emtricitabine and Tenvira (FTC/TDF).
The proportion of subjects who discontinued treatment with Tenvira or PREZCOBIX+FTC/TDF due to adverse events, regardless of severity, were 2% and 4% respectively.
An overview of the most frequent (occurring in at least 2% of subjects) adverse reactions irrespective of severity reported in AMBER are presented in Table 1. An overview of the most frequent laboratory abnormalities of at least Grade 2 severity reported in AMBER are presented in Table 2. Changes from baseline in lipid parameters for patients receiving Tenvira and those receiving PREZCOBIX and F/TDF are presented in Table 3.
Most adverse reactions during treatment with Tenvira were grade 1 or 2 in severity. One grade 3 reaction was reported and no grade 4 adverse reactions were reported during treatment with Tenvira.
| Tenvira (N=362) | PREZCOBIX+FTC/TDF (N=363) | |||
|---|---|---|---|---|
| All Grades | At least Grade 2 | All Grades | At least Grade 2 | |
| ||||
| Diarrhea | 9% | 2% | 11% | 2% |
| Rash* | 8% | 4% | 7% | 5% |
| Nausea | 6% | 1% | 10% | 3% |
| Fatigue | 4% | 1% | 4% | 1% |
| Headache | 3% | 1% | 2% | 1% |
| Abdominal discomfort | 2% | - | 4% | <1% |
| Flatulence | 2% | <1% | 1% | - |
Adverse Reactions in Virologically-Suppressed Adults
The safety profile of Tenvira in virologically-suppressed HIV-1 infected adults is based on Week 48 data from 1,141 subjects in the EMERALD trial, a randomized, open-label, active-controlled trial where 763 subjects with a stable antiretroviral regimen consisting of a boosted protease inhibitor [either darunavir once daily or atazanavir (both boosted with ritonavir or cobicistat), or lopinavir with ritonavir] combined with FTC and TDF switched to Tenvira, and 378 subjects who continued their treatment regimen of a boosted protease inhibitor with FTC and TDF. Overall, the safety profile of Tenvira in subjects in this study was similar to that in subjects with no prior antiretroviral treatment history. The proportion of subjects who discontinued treatment with Tenvira due to adverse events, regardless of severity, was 1%.
Less Frequent Adverse Reactions
The following adverse reactions occurred in less than 2% of adults with no antiretroviral treatment history or virologically suppressed subjects receiving Tenvira, or are from studies described in the prescribing information of the individual component PREZISTA (darunavir).
Gastrointestinal Disorders: dyspepsia, pancreatitis (acute), vomiting
Skin and Subcutaneous Tissue Disorders: angioedema, pruritus, Stevens-Johnson syndrome
Metabolism and Nutrition Disorders: anorexia, diabetes mellitus, lipodystrophy
Reproductive system and Breast disorders: gynecomastia
Musculoskeletal and Connective Tissue Disorders: myalgia, osteonecrosis
Psychiatric Disorders: abnormal dreams
Immune System Disorders: (drug) hypersensitivity, immune reconstitution inflammatory syndrome
Hepatobiliary Disorders: acute hepatitis
Laboratory Abnormalities
| Laboratory Parameter Grade | Limit | Tenvira N=362 | PREZCOBIX+FTC/TDF N=363 |
|---|---|---|---|
| Creatinine | |||
| Grade 2 | >1.3 to 1.8 × ULN | 4% | 14% |
| Grade 4 | ≥3.5× ULN | <1% | 0 |
| Triglycerides | |||
| Grade 2 | 301–500 mg/dL | 7% | 4% |
| Grade 3 | 501–1,000 mg/dL | 1% | 1% |
| Grade 4 | > 1,000 mg/dL | <1%% | <1% |
| Total Cholesterol | |||
| Grade 2 | 240–<300 mg/dL | 17% | 4% |
| Grade 3 | >= 300 mg/dL | 2% | 1% |
| Low-Density Lipoprotein Cholesterol | |||
| Grade 2 | 160–189 mg/dL | 9% | 4% |
| Grade 3 | ≥ 190 mg/dL | 5% | 1% |
| Elevated Glucose Levels | |||
| Grade 2 | 126–250 mg/dL | 6% | 6% |
| Grade 3 | 251–500 mg/dL | <1% | 0 |
ALT and/or AST elevations (Grade 2–4 combined) occurred in 2% of adult subjects receiving Tenvira with no antiretroviral treatment history in AMBER (Week 48 Analysis). Results were consistent in subjects receiving PREZCOBIX+FTC/TDF.
| Tenvira N=356 | PREZCOBIX+FTC/TDF N=355 | |||
|---|---|---|---|---|
| Baseline | Week 48 | Baseline | Week 48 | |
| Mean† | mg/dL | Change | mg/dL | Change |
| N=304‡ | N=290 | |||
| ||||
| Total cholesterol | 168 | +30 | 164 | +11 |
| HDL cholesterol | 45 | +6 | 44 | +2 |
| LDL cholesterol | 199 | +19 | 98 | +5 |
| Triglycerides | 117 | +34 | 112 | +21 |
| Total cholesterol to HDL ratio | 4.1 | 0.2 | 4.0 | 0.1 |
The percentage of subjects starting any lipid lowering drug during treatment in the Tenvira and PREZCOBIX + FTC/TDF arm were 1.7% (n=6) and 0.6% (n=2), respectively.
Renal Laboratory Tests
In the AMBER trial, which had 670 adults with no prior antiretroviral treatment history with a median baseline eGFR of 119 mL/min (Tenvira) and 118 mL/min (PREZCOBIX + FTC/TDF), mean (SD) serum creatinine increased by 0.05 (0.10) mg/dL in the Tenvira group and by 0.09 (0.11) mg/dL in the PREZCOBIX + FTC/TDF group from baseline to Week 48. Median serum creatinine was 0.90 mg/dL (Tenvira) and 0.89 mg/dL (PREZCOBIX + FTC/TDF) at baseline and 0.95 mg/dL (Tenvira) and 0.97 mg/dL (PREZCOBIX +FTC/TDF) at Week 48. Increases in serum creatinine occurred by Week 2 of treatment and remained stable. Median urine protein-to-creatinine ratio (UPCR) was 47 mg per gram (Tenvira) and 51 mg/g (PREZCOBIX + FTC/TDF) at baseline and 30 mg per gram (Tenvira) and 34 mg/g (PREZCOBIX + FTC/TDF) at Week 48.
In the EMERALD trial which had 1,141 virologically-suppressed adults treated with an HIV protease inhibitor and TDF containing regimen with a median baseline eGFR of 104 mL/min (Tenvira) and 103 mL/min (bPI+FTC/TDF) who were randomized to continue their treatment regimen or switch to Tenvira, at Week 48, mean serum creatinine was similar to baseline for both those continuing baseline treatment and those switching to Tenvira. Mean (SD) serum creatinine was 0.98 (0.18) mg/dL (Tenvira) and 0.98 (0.19) mg/dL (bPI+FTC/TDF) at baseline and 0.99 (0.18) mg/dL (Tenvira) and 0.99 (0.21) mg/dL (bPI+FTC/TDF) at Week 48. Median serum creatinine was 0.97 mg/dL (Tenvira) and 0.98 mg/dL (bPI+FTC/TDF) at baseline and 1.0 mg/dL (Tenvira) and 0.97 mg/dL (bPI+FTC/TDF) at Week 48. Median UPCR was 62 mg per gram (Tenvira) and 63 mg/g (bPI+FTC/TDF) at baseline and 37 mg per gram (Tenvira) and 53 mg/g (bPI+FTC/TDF) at Week 48.
Bone Mineral Density
AMBER
The effects of Tenvira compared to PREZCOBIX + FTC/TDF on bone mineral density (BMD) change from baseline to Week 48 were assessed by dual-energy X-ray absorptiometry (DXA). The mean percentage change in BMD from baseline to Week 48 was −0.7% with Tenvira compared to −2.4% with DRV/COBI + FTC/TDF at the lumbar spine and 0.2% compared to −2.7% at the total hip. BMD declines of 5% or greater at the lumbar spine were experienced by 16% of Tenvira subjects and 22% of PREZCOBIX + FTC/TDF subjects. BMD declines of 7% or greater at the femoral neck were experienced by 2% of Tenvira subjects and 15% of PREZCOBIX + FTC/TDF subjects. The long-term clinical significance of these BMD changes is not known.
EMERALD
In EMERALD, boosted Protease Inhibitor (bPI) and TDF-treated subjects were randomized to continue their TDF-based regimen or switch to Tenvira; changes in BMD from baseline to Week 48 were assessed by DXA. The mean percentage change in BMD from baseline to Week 48 was 1.5% with Tenvira compared to −0.6% with PREZCOBIX + FTC/TDF at the lumbar spine and 1.4% compared to -0.3% at the total hip. BMD declines of 5% or greater at the lumbar spine were experienced by 2% of Tenvira subjects and 9% of PREZCOBIX + FTC/TDF subjects. BMD declines of 7% or greater at the femoral neck were experienced by no Tenvira subjects and 2% of PREZCOBIX + FTC/TDF subjects. The long-term clinical significance of these BMD changes is not known.
Postmarketing Experience
The following adverse reactions have been identified during postmarketing experience in patients receiving a darunavir-containing regimen. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Metabolism and Nutrition Disorders
Redistribution of body fat
Musculoskeletal and Connective Tissue Disorders
Rhabdomyolysis (associated with co-administration with HMG-CoA reductase inhibitors)
Skin and Subcutaneous Tissue Disorders
Toxic epidermal necrolysis, acute generalized exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms.
What is the most important information I should know about Tenvira?
- Tenvira powder may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Tenvira powder with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
- If you have HIV infection, you should be tested for HBV infection before you start to take Tenvira powder. If you have HBV infection, you should be tested for HIV infection before you start to take Tenvira powder.
- Do NOT take more than the recommended dose, change your dose, or stop taking Tenvira powder or any of your medicines without checking with your doctor.
- Keep a list of all the medicines that you take. Make a new list each time medicines are added or stopped. Find out about medicines that should not be taken while you are using Tenvira powder. Be sure that each of your health care providers knows all the medicines that you are taking.
- When your medicine supply is low, get more from your doctor or pharmacist as soon as you can. Do not stop taking Tenvira powder, even for a short period of time. If you do, the virus may grow resistant to the medicine and become harder to treat.
- Tenvira powder is not a cure for HIV or HBV infection. Patients infected with HIV may still get illnesses and infections associated with the disease. Remain under the care of your doctor.
- Tenvira powder does not stop the spread of HIV or HBV to others through blood or sexual contact. Do not have any kind of sex without protection (eg, latex or polyurethane condoms) if you have HIV or HBV infection. Do not share needles, injection supplies, or items like toothbrushes or razors. Talk with your health care provider about ways to prevent the spread of HIV or HBV to others.
- If you have HBV infection, you will need close medical follow-up for several months after stopping treatment with Tenvira powder. Follow-up includes medical exams and blood tests to check for HBV infection that could be getting worse.
- Tenvira powder may improve immune system function. This may reveal hidden infections in some patients. Tell your doctor right away if you notice symptoms of infection (eg, fever, sore throat, weakness, cough, shortness of breath) after you start Tenvira powder.
- Check with your doctor to see if you should take a calcium and vitamin D supplement while you are taking Tenvira powder.
- The risk of severe side effects (eg, lactic acidosis, severe liver problems) may be greater in women, patients who are very overweight (obese), and patients who have taken nucleoside medicines (eg, emtricitabine, Tenvira) for a long time. Talk with your doctor if you have questions about your risk for severe side effects from Tenvira powder.
- Changes in body fat (eg, an increased amount of fat in the upper back, neck, breast, and trunk, and loss of fat from the legs, arms, and face) may occur in some patients taking Tenvira powder. The cause and long-term effects of these changes are unknown. Discuss any concerns with your doctor.
- Tell your doctor or dentist that you take Tenvira powder before you receive any medical or dental care, emergency care, or surgery.
- Lab tests, including liver and kidney function and bone mineral density, may be performed while you use Tenvira powder. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
- Use Tenvira powder with extreme caution in CHILDREN younger than 2 years old; safety and effectiveness in these children have not been confirmed.
- The dose of Tenvira powder in CHILDREN is determined based on body weight; they will need to have regular weight checks while they take Tenvira powder.
- PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Tenvira powder while you are pregnant. It is not known if Tenvira powder is found in breast milk. Mothers infected with HIV should not breast-feed. There is a risk of passing the HIV infection or Tenvira powder to the baby. Do not breast-feed while taking Tenvira powder.
Tenvira contraindications
Tenvira is contraindicated with the following co-administered drugs due to the potential for serious and/or life-threatening events or loss of therapeutic effect.
- Alpha 1-adrenoreceptor antagonist: alfuzosin
- Antianginal: ranolazine
- Antiarrhythmic: dronedarone
- Anticonvulsants: carbamazepine, phenobarbital, phenytoin
- Anti-gout: colchicine, in patients with renal/and or hepatic impairment
- Antimycobacterial: rifampin
- Antipsychotics: lurasidone, pimozide
- Ergot derivatives, e.g., dihydroergotamine, ergotamine, methylergonovine
- GI motility agent: cisapride
- Herbal product: St. John's wort (Hypericum perforatum)
- Hepatitis C direct acting antiviral: elbasvir/grazoprevir
- HMG-CoA reductase inhibitors: lovastatin, simvastatin
- PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension
- Sedatives/hypnotics: orally administered midazolam, triazolam
References
- DailyMed. "EMTRICITABINE; RILPIVIRINE HYDROCHLORIDE; TENOFOVIR DISOPROXIL FUMARATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- European Chemicals Agency - ECHA. "2,4,6,8-Tetraoxa-5-phosphanonanedioic acid, 5-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]-, 1,9-bis(1-methylethyl) ester, 5-oxide: The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness.". https://echa.europa.eu/ (accessed September 17, 2018).
- HSDB. "TENOFOVIR DISOPROXIL FUMARATE". https://toxnet.nlm.nih.gov/cgi-bin/s... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Tenvira are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Tenvira. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported side effects
No survey data has been collected yetConsumer reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
