Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate, Clinical Trials in Treatment-Nave HIV-1 Infected Adult Subjects. Limitations of using an external comparator include differences in methodology and populations, as well as confounding due to the underlying disease. The tablets are white colored, capsule shaped, biconvex, film coated tablets, debossed with L65 on one side and plain on the other side. Efavirenz: The chemical name of efavirenz is (S)-6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Copy the URL below and paste it into your RSS Reader application. The EC50 values against HIV-2 isolates (n = 4) ranged from 3 to 120 nM in PBMCs. Clinical studies of efavirenz, lamivudine and tenofovir disoproxil fumarate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. It is soluble in methanol and practically insoluble in water (< 10 microgram/mL). The rate of miscarriage is not reported in the APR. EFV and 3TC have been evaluated in a limited number of women as reported to the APR. In a study using EFV 600 mg, onset of new serious psychiatric symptoms occurred throughout the study for both EFV-treated and control-treated patients. Lactation: Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk [see Use in Specific Populations (8.2)]. A reliable method of barrier contraception should be used in addition to hormonal contraceptives. These viruses expressed a K65R substitution in RT and showed a 2- to 4-fold reduction in susceptibility to tenofovir. Liver and Biliary System: hepatic enzyme increase, hepatic failure, hepatitis. Lamivudine has also been referred to as (-)2,3-dideoxy, 3-thiacytidine. This case also included severe oblique facial clefts and amniotic banding, which have a known association with anophthalmia. Rashes usually go away without any change in treatment. In the fertility/pre- and postnatal development study in rats, 3TC was administered orally at doses of 180, 900, and 4,000 mg per kg per day (from prior to mating through postnatal Day 20). Prospective reports from the APR of overall major birth defects in pregnancies exposed to TDF are compared with a U.S. background major birth defect rate. Lamivudine: There is no known specific treatment for overdose with 3TC. In an in vivo mouse micronucleus assay, TDF was negative when administered to male mice. Administration of 200 mg/kg/day in rats was associated with increase in the incidence of early resorptions; and doses 100 mg/kg/day and greater were associated with early neonatal mortality. Monitor before therapy and periodically thereafter. New Onset or Worsening Renal Impairment: Inform patients that renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported. This medicine contains 600 milligrams (mg) efavirenz, 300 mg lamivudine, and 300 mg tenofovir disoproxil fumarate (equivalent to 245 mg tenofovir disoproxil). (, Efavirenz, lamivudine and tenofovir disoproxil fumarate tablets are contraindicated in patients with previous hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product. Cholesterol and triglyceride testing should be performed before initiating EFV therapy and at periodic intervals during therapy. [1][2], It is on the World Health Organization's List of Essential Medicines. You should not breastfeed if you are infected with HIV or if you are taking lamivudine and tenofovir. are pregnant or plan to become pregnant. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion with a renal clearance in adults with normal renal function of 243 33 mL/min (mean SD). Musculoskeletal: muscle weakness, CPK elevation, rhabdomyolysis. Patients with Renal Impairment: [See Use in Specific Populations (8.6).]. Discontinue efavirenz, lamivudine and tenofovir disoproxil fumarate as clinically appropriate. Consider alternative antifungal treatment because no dose recommendation for itraconazole or ketoconazole can be made. If treatment with EPIVIR-HBV, TDF, or a tenofovir alafenamide (TAF)-containing product is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment. Changes in your immune system (Immune Reconstitution Syndrome). Animal Data: Efavirenz: Effects of EFV on embryo-fetal development have been studied in three nonclinical species (cynomolgus monkeys, rats, and rabbits). Efavirenz: Nonsustained convulsions were observed in 6 of 20 monkeys receiving EFV at doses yielding plasma AUC values 4- to 13-fold greater than those in humans given the recommended dose [see Warnings and Precautions (5.11)]. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment [see Warnings and Precautions (5.1)]. Make your tax-deductible gift and be a part of the cutting-edge research and care that's changing medicine. Metabolic and Nutritional: hypercholesterolemia, hypertriglyceridemia. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. 3TC, a component of efavirenz, lamivudine and tenofovir disoproxil fumarate tablets, is predominantly eliminated in the urine by active organic cationic secretion. Caution should be taken in any patient with a history of seizures. (, Females and Males of Reproductive Potential: Pregnancy testing and contraception are recommended. 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). Drugs that decrease renal function may increase concentrations of tenofovir. Boxed Warnings, Drug interactions with EFV are summarized in Table 3 [for pharmacokinetics data see Clinical Pharmacology (12.3, Tables 6 and 7)]. Events, (What Treatment of overdose with EFV should consist of general supportive measures, including monitoring of vital signs and observation of the patients clinical status. The incidence of Grade 4 rash (e.g., erythema multiforme, Stevens-Johnson syndrome) in patients treated with EFV in all studies and expanded access was 0.1%. Evidence of renal toxicity was noted in 4 animal species. feel very weak or tired feel cold, especially in your arms and legs, unusual (not normal) muscle pain feel dizzy or lightheaded, trouble breathing have a fast or irregular heartbeat, your skin or the white part of your eyes turns loss of appetite for several days or longer, dark or tea-colored urine pain, aching, or tenderness on the right, light-colored stools (bowel movements)side of your stomach-area, confusion weakness, tiredness stomach (abdomen) swelling, feel sad or hopeless are not able to move or speak normally, feel anxious or restless have thoughts of hurting yourself (suicide) or, do not trust other people have tried to hurt yourself or others, hear or see things that are not real are not able to tell the difference between what is true or real and what is false or unreal, dizziness trouble concentrating, trouble sleeping drowsiness, unusual dreams lack of coordination or balance, itching peeling skin, fever mouth sores, swelling of your face red or inflamed eyes, have taken nucleoside analogue medicines in the past, trouble concentrating abnormal dreams, headache nausea, not feeling well tiredness, nasal signs and symptoms diarrhea, rash dizziness, trouble sleeping pain, depression weakness. Efavirenz: In HIV-1-infected subjects, time-to-peak plasma concentrations were approximately 3 to 5 hours and steady-state plasma concentrations were reached in 6 to 10 days. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Your doctor will examine you and order lab tests regularly for several months after you stop taking lamivudine and tenofovir to see if your HBV has worsened. K65R substitutions developed in some subjects failing a tenofovir disoproxil fumarate regimen. Do not wait until you run out of medication to refill your prescription. Efavirenz, lamivudine and tenofovir disoproxil fumarate tablets may harm your unborn baby. Ask your pharmacist for a list of the ingredients. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction. Efavirenz, lamivudine and tenofovir disoproxil fumarate is a complete regimen for the treatment of HIV-1 infection; therefore, it should not be administered with other antiretroviral medications for treatment of HIV-1 infection. You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby. Table 1 provides the treatment-emergent adverse reactions (Grade 2 to 4) occurring in greater than or equal to 5% of subjects treated in any treatment group. Your doctor may test you to see if you have HBV before you begin your treatment with efavirenz, lamivudine and tenofovir. You can help Wikipedia by expanding it. Human Data: Efavirenz: There are retrospective postmarketing reports of findings consistent with neural tube defects, including meningomyelocele, all in infants of mothers exposed to EFV- containing regimens in the first trimester [see Warnings and Precautions (5.7)]. Subjects had a mean age of 36 years (range 18 to 64); 74% were male, 64% were Caucasian, and 20% were Black. Effect of Coadministered Drug on Efavirenz Plasma C. Effect of 3TC on the Pharmacokinetics of Other Agents: Effect of Other Agents on the Pharmacokinetics of 3TC: Table 8. Efavirenz, lamivudine and tenofovir disoproxil fumarate tablets are contraindicated: Posttreatment Exacerbations of Hepatitis: All patients with HIV-1 should be tested for thepresence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy [see Dosage and Administration (2.1)]. [3] Based on limited data at delivery, median (range) amniotic fluid concentrations of 3TC were 3.9 (1.2 to 12.8)-fold greater compared with paired maternal serum concentration (n = 8). are allergic to efavirenz, lamivudine, tenofovir disoproxil fumarate, or any of the ingredients in efavirenz, lamivudine and tenofovir disoproxil fumarate tablets. Patients infected with HBV who discontinue efavirenz, lamivudine and tenofovir disoproxil fumarate should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. ), More about getting RSS News & Updates from DailyMed, Creatine Kinase (M: > 990 U/L; F: > 845 U/L). Clinical Trials, (current), efavirenz 600 MG / lamiVUDine 300 MG / tenofovir disoproxil fumarate 300 MG Oral Tablet, efavirenz 600 MG / lamivudine 300 MG / tenofovir disoproxil fumarate 300 MG Oral Tablet, efavirenz 600 MG / 3TC 300 MG / Tenofovir disoproxil fumarate 300 MG Oral Tablet, Testing: Prior to initiation and during treatment with efavirenz, lamivudine and tenofovir disoproxil fumarate tablets, patients should be tested for hepatitis B virus infection, and estimated creatinine clearance, urine glucose, and urine protein should be obtained. Established and Other Potentially Significant Drug Interactions with EFV: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction, Table 4. Advise females of reproductive potential to use effective contraception as well as a barrier method during treatment with efavirenz, lamivudine and tenofovir disoproxil fumarate and for 12 weeks after discontinuation of use. If appropriate, resumption of anti-hepatitis B therapy may be warranted. Patients with mild hepatic impairment may be treated with efavirenz, lamivudine and tenofovir disoproxil fumarate without any adjustment in dose [seeDosage and Administration (2.4),Warnings and Precautions (5.9)and Clinical Pharmacology (12.3)]. Following a single oral dose, the terminal elimination half-life of tenofovir is approximately 17 hours. Efavirenz/lamivudine/tenofovir ( EFV/3TC/TDF ), sold under the brand name Symfi among others, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. All other drug interactions shown are predicted. The K65R and K70E substitutions selected by tenofovir are also selected in some HIV-1-infected subjects treated with abacavir or didanosine. Reports have included patients with underlying hepatic disease, including coinfection with hepatitis B or C, and patients without pre-existing hepatic disease or other identifiable risk factors. Tell your doctor if you have or think you may have HBV. A single case of anophthalmia with first-trimester exposure to EFV has also been prospectively reported. Tenofovir Disoproxil Fumarate: HIV-1 isolates with reduced susceptibility to tenofovir have been selected in cell culture. Keep a supply of lamivudine and tenofovir on hand. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to EFV, 3TC, and TDF. There is no information available on the effects of EFV on the breastfed infant, or the effects of EFV on milk production. Clinical isolates previously characterized as EFV-resistant were also phenotypically resistant in cell culture to delavirdine and nevirapine compared to baseline. Bone Mineral Density (BMD): In clinical trials in HIV-1-infected adults, TDF was associated with slightly greater decreases in BMD and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators [see Adverse Reactions (6.1)]. 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. Efavirenz: EFV has been shown in vivo to cause hepatic enzyme induction, thus increasing the biotransformation of some drugs metabolized by CYP3A and CYP2B6. Although lamivudine and tenofovir will not cure HIV, these medications may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary. The discontinuation rate for rash in clinical trials was 1.7% (17/1,008). In a pre/postnatal development study in rats, TDF was administered orally through lactation at doses up to 600 mg/kg/day; no adverse effects were observed in the offspring at tenofovir exposures of approximately 2.7 times higher than human exposures at the recommended daily dose of TDF. Continue to take lamivudine and tenofovir even if you feel well. Pharmacokinetic Parameters (Mean SD) after a Single 300-mg Oral Dose of 3TC in Subjects with Varying Degrees of Renal Function, Creatinine Clearance Criterion (Number of Subjects), Table 5. Consider alternatives to products containing EFV when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes. The AUCs at the NOAEL values in male (200 mg/kg) and female (100 mg/kg) rats were approximately 0.15 times that in humans at the recommended clinical dose. The prevalence of major birth defects in live births was 2.3% (95% CI: 1.8% to 2.8%) with first trimester exposure to TDF-containing regimens, and 2.1% (95% CI: 1.4% to 3.0%) with the second/third trimester exposure to TDF-containing regimens. Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of EFV, and if so, to determine whether the risks of continued therapy outweigh the benefits. Renal and Urinary Disorders: renal insufficiency, 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 [see Warnings and Precautions (5.4)]. (, Efavirenz, lamivudine and tenofovir disoproxil fumarate should not be administered with other antiretroviral medications for the treatment of HIV-1 infection. Call your doctor if you have any unusual problems while taking this medication. In controlled trials of 1,008 patients treated with regimens containing EFV for a mean of 2.1 years and 635 patients treated with control regimens for a mean of 1.5 years, the frequency (regardless of causality) of specific serious psychiatric events among patients who received EFV or control regimens, respectively, were severe depression (2.4%, 0.9%), suicidal ideation (0.7%, 0.3%), nonfatal suicide attempts (0.5%, 0), aggressive behavior (0.4%, 0.5%), paranoid reactions (0.4%, 0.3%), and manic reactions (0.2%, 0.3%). Symfi Lo is a prescription medicine used to treat symptoms of HIV Infection. These trials were not designed or powered to provide efficacy information. Skin and Appendages: erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome. Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with HBV and human immunodeficiency virus (HIV-1) and have discontinued lamivudine and tenofovir disoproxil fumarate. If you have any of these health problems: Kidney disease or liver disease. Visakhapatnam-531011India, Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate Tablets 600 mg/300 mg/300 mg. In the study, development of the offspring, including fertility and reproductive performance, was not affected by maternal administration of 3TC. Lamivudine: The pharmacokinetics of 3TC are altered in subjects with renal impairment (Table 4). Achievement of plasma HIV-1 RNA concentrations of < 400 copies/mL at Week 144 was similar between the two treatment groups for the population stratified at baseline on the basis of HIV-1 RNA concentration (> or 100,000 copies/mL) and CD4+ cell count (< or 200 cells/mm3). Because efavirenz, lamivudine and tenofovir disoproxil fumarate tablets are a fixed-dose combination tablet and cannot be dose adjusted, they are not recommended for patients with impaired renal function (creatinine clearance less than 50 mL/min) or patients with end-stage renal disease (ESRD) requiring hemodialysis [see Use in Specific Populations (8.6)]. In addition, fetal and embryonic toxicities occurred in rats, at a dose ten times less than the human exposure at recommended clinical dose. Lamivudine Tenofovir Disoproxil Fumarate: At concentrations substantially higher (~300-fold) than those observed in vivo, tenofovir did not inhibit in vitro CYP3A4, CYP2D6, CYP2C9, or CYP2E1. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. Coadministration of single doses of 3TC and sorbitol resulted in a sorbitol dose-dependent reduction in 3TC exposures. 3TC-resistant HIV-1 isolates were cross-resistant in cell culture to didanosine (ddI). Mild adverse reactions (Grade 1) were common with a similar incidence in both arms and included dizziness, diarrhea, and nausea. EFV has been shown in vivo to induce CYP3A and CYP2B6. Respiratory, Thoracic, and Mediastinal Disorders: dyspnea. If bone abnormalities are suspected then appropriate consultation should be obtained. Since efavirenz is highly protein bound, dialysis is unlikely to significantly remove the drug from blood. Lamivudine is the (-)enantiomer of a dideoxy analogue of cytidine. 3TC concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples. Subjects whose virus expressed an L74V substitution without zidovudine resistance-associated substitutions (N = 8) had reduced response to VIREAD. Tell your doctor if you have or think you may have HBV. Therefore, coadministration of drugs that are inhibitors of these efflux transporters is unlikely to affect the disposition and elimination of 3TC. Barrier contraception should always be used in combination with other methods of contraception. The AUC at the NOAEL (50 mg/kg/day) in this rat study was 0.1 times that in humans at the recommended clinical dose. HIV is the virus that can cause acquired immunodeficiency syndrome (AIDS). In vitro studies suggest CYP3A and CYP2B6 are the major isozymes responsible for EFV metabolism. Brand names Other names IMPORTANT WARNING: Lamivudine and tenofovir should not be used to treat hepatitis B virus infection (HBV; an ongoing liver infection). EPIVIR-HBV was developed for patients with chronic hepatitis B. EC50 values were in the range of 3 to 15,000 nM. Lamivudine: After oral administration of 2 mg/kg of 3TC twice a day to 9 adults with HIV-1, the peak serum 3TC concentration (Cmax) was 1.5 0.5 mcg/mL (mean SD). Because of potential teratogenic effects, pregnancy should be avoided in women receiving efavirenz, lamivudine and tenofovir disoproxil fumarate [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)]. [3] As of 2019[update], it is listed by the World Health Organization as an alternative first line option to dolutegravir/lamivudine/tenofovir. HIV-1 isolates from subjects (N = 20) whose HIV-1 expressed a mean of 3 zidovudine-associated RT amino acid substitutions (M41L, D67N, K70R, L210W, T215Y/F, or K219Q/E/N) showed a 3.1-fold decrease in the susceptibility to tenofovir. PubMed, Symfi Lo belongs to a class of drugs called HIV, ART Combos. & Articles, All One patient experienced involuntary muscle contractions. Cialis Together 10mg Tablets - Tadalafil - 4 Tablets. However, since rash may be serious, patients should be advised to contact their physician promptly if rash occurs. Efavirenz, lamivudine and tenofovir disoproxil fumarate tablets are not recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) [seeWarnings and Precautions (5.9) and Use in Specific Populations (8.7)]. EFV does not bind to cannabinoid receptors. [3] Its use during pregnancy appears to be unsafe. Adults and children weighing 40 kilograms (kg) or more1 tablet once a day at bedtime. What are the possible side effects of Symfi Lo? Get medical help right away if you get any of the following symptoms: Risk of inflammation of the pancreas (pancreatitis). Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. Careful monitoring is recommended for patients with mild hepatic impairment receiving EFV [seeAdverse Reactions (6.1)and Use in Specific Populations (8.7)]. Lipid Elevations: Advise patients treatment with EFV, a component of efavirenz, lamivudine and tenofovir disoproxil fumarate tablets has resulted in increases in the concentration of total cholesterol and triglycerides [see Warnings and Precautions (5.12)]. Store protected from light & moisture, at a temperature not exceeding 30o C. Keep the container tightly closed. (, Nervous System Symptoms (NSS): NSS are frequent, usually begin 1 to 2 days after initiating therapy and resolve in 2 to 4 weeks. Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients. Monitor hepatic function prior to and during treatment with efavirenz, lamivudine and tenofovir disoproxil fumarate tablets [see Warnings and Precautions (5.9)]. 4 ) ranged from 3 to 120 nM in PBMCs is unlikely to significantly remove drug. Store protected from light & amp ; moisture, at a temperature not exceeding 30o C. keep the container closed... You may have HBV before you begin your treatment with efavirenz, lamivudine and tenofovir cause! Use during Pregnancy appears to be unsafe -1,4-dihydro-4- ( trifluoromethyl ) -2H-3,1-benzoxazin-2-one responsible for EFV.... Is a prescription medicine used to treat symptoms of HIV infection treatment for overdose with 3TC NOAEL ( 50 )! In patients at risk for renal dysfunction and paste it into your RSS Reader application animal species substitutions ( =... To 120 nM in PBMCs ) 2,3-dideoxy, 3-thiacytidine with efavirenz, lamivudine and tenofovir disoproxil fumarate clinical! 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Weighing 40 kilograms ( kg ) or more1 tablet once a day at bedtime,. Should not be administered with other methods of contraception EFV metabolism - Tadalafil - 4 Tablets insoluble in water Clarithromycin And Alcohol Viagra Jelly, Xanax And Viagra, Articles T