Abacavir; lamivudine; zidovudine is a combination of 3 nucleoside analog reverse transcriptase inhibitors (NRTIs), approved for the treatment of human immunodeficiency virus (HIV) infection. The drug was initially developed to preserve both protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) for later use. However, abacavir; lamivudine; zidovudine is not considered a highly active antiretroviral therapy (HAART) and HIV guidelines recommend against the use of this triple NRTI therapy because of inferior virologic efficacy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Screen for HLA-B*5701 before initiating treatment to reduce the risk of hypersensitivity reaction. HLA-B*5701-positive patients MUST not receive abacavir.
Hazardous Drugs Classification
-Abacavir and zidovudine are classified as hazardous drugs.
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.
Route-Specific Administration
Oral Administration
-Administer with or without food.
This section discusses adverse reactions reported with the combination product Trizivir. Refer to the individual monographs for abacavir, lamivudine, or zidovudine for specific information concerning adverse events related to the individual agents.
Gastrointestinal adverse events that occurred during combination therapy with abacavir, lamivudine, and zidovudine include nausea (19%), nausea plus vomiting (10%), and diarrhea (7%). Adverse events noted in postmarketing reports with any of the 3 components include stomatitis, anorexia, decreased appetite, abdominal pain, dyspepsia, and oral mucosal pigmentation.
During clinical trials with abacavir; lamivudine; zidovudine, malaise and fatigue (12%), fever or chills (6%), and nonspecific pain (less than 1%) were reported. Vasculitis and weakness were noted in postmarketing reports.
Bone marrow suppression, resulting in anemia, neutropenia (5%), or thrombocytopenia, has been reported in some patients receiving abacavir; lamivudine; zidovudine due to the zidovudine component. Aplastic anemia, red cell aplasia, thrombocytopenia, and splenomegaly have also been reported postmarketing.
Myopathy and myositis, with pathological changes similar to that produced by HIV disease, have been associated with prolonged use of zidovudine, and may occur with abacavir; lamivudine; zidovudine. During clinical trials of abacavir; lamivudine; zidovudine, musculoskeletal pain was reported in 5% of patients and creatine phosphokinase (CPK) greater than 4-time upper limit of normal was reported in 7% of drug recipients. Arthralgia, myalgia, muscle weakness, and rhabdomyolysis have been noted in postmarketing reports.
Hepatic and renal symptoms have been reported with the use of abacavir; lamivudine; zidovudine. Renal signs and symptoms have been reported in less than 1% of patients. Elevated hepatic enzymes (6%), hypertriglyceridemia (2%), hyperamylasemia (2%), hyperbilirubinemia (postmarketing), and mild hyperglycemia (less than 1%) have been reported. Lactic acidosis and severe hepatotoxicity (i.e., fatal cases of hepatomegaly with steatosis) have been reported with the use of nucleoside reverse transcriptase inhibitors, including abacavir, lamivudine, and zidovudine. Many of these cases have occurred in women. Abacavir; lamivudine; zidovudine should be discontinued if a patient develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity, including hepatomegaly and steatosis even in the absence of marked elevated transaminases. Pancreatitis has been reported during treatment.
Zidovudine has been associated with loss of subcutaneous fat, particularly in the face, limbs, and buttocks. The mechanism by which nucleoside analogues may cause body fat changes is not known; however, it has been suggested that nucleoside analogs may damage the mitochondria of adipocytes. The incidence and severity of these body fat changes are related to cumulative exposure. Switching to a non-zidovudine-containing regimen may only partially reverse these changes, and improvement may take months to years to achieve. Regularly assess patients for signs of lipodystrophy. If feasible, therapy should be switched to an alternative regimen.
Skin rash was reported in 5% of patients receiving abacavir; lamivudine; zidovudine during clinical trials. During postmarketing surveillance, cases of alopecia and erythema multiforme have been reported. Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN; because of the overlap of clinical signs and symptoms between SJS and TEN and hypersensitivity to abacavir, and the possibility of multiple drug sensitivities in some patients, abacavir; lamivudine; zidovudine should be discontinued and not restarted in such cases.
Nervous system or psychiatric adverse events reported with abacavir; lamivudine; zidovudine include headache (13%), depression (6%), worsening of depression, and anxiety (5%). Dizziness, paresthesias, peripheral neuropathy, seizures, insomnia, and other sleep disorders were noted in postmarketing reports.
Infection of the ear/nose/throat (5%) and viral respiratory infections (5%) were reported with the use of abacavir; lamivudine; zidovudine.
Cardiomyopathy has been noted during postmarketing use of abacavir; lamivudine; zidovudine. Additionally, treatment with abacavir was linked with the development of myocardial infarction (MI) in several prospective, observational, epidemiologic trials. In contrast to these trials, a meta-analysis of 26 randomized clinical trials conducted by the FDA failed to reveal an association between treatment with abacavir-containing regimens and development of MI (OR = 1.02; 95% CI: 0.56 to 1.84). In light of the conflicting data, caution is advised when prescribing abacavir; lamivudine; zidovudine to patients with pre-existing coronary heart disease. Healthcare providers are encouraged to minimize a patient's modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, and smoking) prior to prescribing abacavir; lamivudine; zidovudine.
Wheezing and abnormal breath sounds have been noted in postmarketing reports with abacavir; lamivudine; zidovudine.
Serious hypersensitivity reactions or anaphylaxis, including fatal reactions, have occurred in patients receiving abacavir. In clinical trials, the incidence of hypersensitivity reactions to abacavir was 8% when HLA-B*5701 screening was not performed; the incidence was 1% when HLA-B*5701-positive patients were excluded. Signs and symptoms of hypersensitivity include fatigue, fever, chills, skin rash, gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting), and respiratory symptoms including pharyngitis, dyspnea, or cough. Respiratory symptoms occur in approximately 20% of patients with abacavir hypersensitivity reactions. Other signs and symptoms include malaise, lethargy, myalgia, arthralgia, edema, and paresthesias. Physical findings include lymphadenopathy, mucous membrane lesions (conjunctivitis and oral ulceration), and rash. The rash, if present, usually appears as a maculopapular rash or urticarial rash (urticaria) but may be variable in appearance. There have been reports of erythema multiforme. Laboratory findings include elevated liver enzymes, increased creatine phosphokinase, increased creatinine/BUN (azotemia), and lymphopenia. Deaths have been reported in patients receiving abacavir who were initially diagnosed with an acute respiratory disease (pneumonia, bronchitis, or flu-like illness) who were later recognized to have had a hypersensitivity reaction to abacavir that included respiratory symptoms. A delay in diagnosis of abacavir hypersensitivity can result in abacavir being continued or reintroduced, leading to more severe hypersensitivity reactions including, life-threatening hypotension, anaphylactoid reactions, hepatic failure, renal failure (unspecified), acute respiratory distress syndrome (ARDS), respiratory arrest, and death. Symptoms usually appear within the first 6 weeks of treatment, although these reactions may occur at any time during therapy. Hypersensitivity reactions have been reported upon reintroduction of abacavir therapy that has been discontinued for other medical reasons. In a minority of these patients, hypersensitivity occurred days or weeks after reintroduction of abacavir treatment. Symptoms worsen with continued therapy but often resolve upon discontinuation of the drug. Patients developing signs or symptoms of hypersensitivity should discontinue use of abacavir as soon as a hypersensitivity reaction is suspected. In patients presenting with symptoms of acute respiratory disease and other symptoms associated with hypersensitivity to abacavir, a hypersensitivity reaction should be suspected even if alternative respiratory diagnoses are possible. If the clinical presentation of an acute illness cannot be clearly differentiated from a hypersensitivity reaction, abacavir should be permanently discontinued. Patients should never be restarted on any abacavir containing product following a hypersensitivity reaction because more severe symptoms will recur within hours of administration and may include life-threatening hypotension and death. To facilitate reporting of hypersensitivity reactions and collection of information on each case, health care professionals should report all hypersensitivity reactions to the Abacavir Hypersensitivity Registry at Glaxo Wellcome by calling 800-270-0425 or the FDA MedWatch program at 800-FDA-1088.
Severe acute hepatitis B exacerbation has been reported in patients coinfected with HIV and the hepatitis B virus (HBV) who have discontinued treatment with lamivudine. If use of abacavir; lamivudine; zidovudine is stopped in a coinfected patient, closely monitor hepatic function with both clinical and laboratory follow-up for at least several months. If appropriate, treatment for hepatitis B infection may be warranted. Prior to initiating antiretroviral therapy for the treatment of HIV, it is recommended that all patients be tested for the presence of chronic HBV.
Zidovudine is associated with a decrease in vitamin B12 concentrations in patients with HIV and may lead to vitamin B12 deficiency. Regular monitoring and supplementation may be necessary.
During baseline evaluation of people with HIV, discuss risk reduction measures and the need for status disclosure to sexual or needle-sharing partners, especially with untreated patients who are still at high risk of HIV transmission. Include the importance of adherence to therapy to achieve and maintain a plasma HIV RNA less than 200 copies/mL. Maintaining a plasma HIV RNA less than 200 copies/mL, including any measurable value below this threshold, with antiretroviral therapy prevents sexual transmission of HIV to their partners. Patients may recognize this concept as Undetectable = Untransmittable or U=U. Instruct patients to achieve sustained viral suppression (i.e., 2 recorded measurements of plasma viral loads that are below the limits of detection and taken at least 3 months apart) before attempting to conceive a child in order to maximize their health, prevent HIV sexual transmission, and minimize the risk of HIV transmission to the infant once conception occurs. For partners with different HIV status when the person with HIV is on antiretroviral therapy and has achieved sustained viral suppression, sexual intercourse without a condom allows conception without sexual HIV transmission to the person without HIV. Expert consultation is recommended.
Unplanned antiretroviral therapy interruption may be necessary for specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., less than 1 to 2 days) is necessary, in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption occurs in a pregnant patient or is because of a serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered; as stopping all simultaneously in a regimen containing drugs with differing half-lives may result in functional monotherapy of the drug with the longest half-life and may increase the risk for resistant mutations. Healthcare providers are advised to reinitiate a complete and effective antiretroviral regimen as soon as possible after an interruption of therapy. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.
Abacavir has been associated with serious hypersensitivity reactions or anaphylaxis (some cases have been fatal); to reduce the risk, perform HLA-B*5701 testing on all patients before initiating treatment. Abacavir is contraindicated in any HLA-B*5701-positive patient; clearly record the positive status as an abacavir allergy in the patients' medical record. According to the manufacturer, the estimated incidence of hypersensitivity to abacavir was 8% when HLA-B*5701 screening was not performed; the incidence was 1% when HLA-B*5701-positive patients were excluded. Racial background may help identify those at higher risk for carrying the HLA-B*5701 gene, as in the United States approximately 8% of Caucasian patients, 2.5% of Black patients, and 1% of Asian patients are carriers. Regardless of HLA-B*5701 status, immediately discontinue treatment in patients developing or with suspected signs or symptoms of abacavir hypersensitivity, including those presenting with 2 or more of the following: fever, rash, gastrointestinal (e.g., nausea, vomiting, diarrhea, abdominal pain), constitutional (generalized malaise, fatigue, achiness), or respiratory (dyspnea, cough, pharyngitis). Permanently discontinue abacavir if the clinical presentation of an acute illness cannot be clearly differentiated from a hypersensitivity reaction. NEVER reinitiate an abacavir containing product in a patient who experiences a hypersensitivity reaction as more severe symptoms will recur within hours of administration and may include life-threatening hypotension and death. Severe or fatal hypersensitivity reactions may also occur within hours after abacavir reintroduction in patients who have no identified history of hypersensitivity, but who stopped abacavir for reasons unrelated to symptoms of hypersensitivity (e.g., interruption in drug supply or discontinuation while treating other medical conditions). In some cases, symptoms consistent with hypersensitivity may have been present before abacavir was discontinued, but may have been attributed to other medical conditions (e.g., acute onset respiratory diseases, gastroenteritis, or reactions to other medications). In a minority of cases, hypersensitivity reactions occurred days to weeks after abacavir reintroduction. If abacavir has been discontinued for reasons other than symptoms of hypersensitivity and if reinitiation is being considered, re-evaluate the reason for discontinuation and ensure that the patient did not have any suspected symptoms of hypersensitivity. If hypersensitivity symptoms are suspected upon review, do not reinitiate abacavir. If symptoms consistent with hypersensitivity are not identified and the patient is HLA-B*5701-negative, undertake reintroduction with caution. If HLA-B*5701 status is unknown, screening should occur prior to restarting therapy. Health care professionals should report all hypersensitivity reactions to the FDA MedWatch program (800-FDA-1088).
Clinical studies of abacavir, lamivudine, or zidovudine did not include sufficient numbers of patients aged 65 years or over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in response between geriatric and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Abacavir; lamivudine; zidovudine is not recommended for use in neonates, infants, or children who weigh less than 40 kg, because it is a fixed-dose tablet that cannot be adjusted for this population.
The combination product of abacavir; lamivudine; zidovudine is not recommended for use in patients with renal impairment (i.e., creatinine clearance less than 50 mL/minute) or renal failure. Because the drug is a fixed-dose tablet, the dosages of the individual components cannot be adjusted for renal function.
Patients with preexisting bone marrow suppression especially neutropenia (granulocyte count less than 1,000 cells/mm3) or anemia (hemoglobin less than 9.5 g/dL) should receive abacavir; lamivudine; zidovudine therapy with caution. Other patients that may be at increased risk for bone marrow toxicity include those with folate deficiency or vitamin B12 deficiency. Cytotoxic drugs or radiation therapy may also increase the risk of myelosuppression. HIV guidelines recommend monitoring complete blood counts (CBC) with differential at entry to care and before initiating or modifying treatment. For patients started on abacavir; lamivudine; zidovudine, a follow-up CBC with differential should be obtained after 2 to 8 weeks of treatment, followed by periodic monitoring every 3 to 6 months or as clinically indicated.
Abacavir; lamivudine; zidovudine is contraindicated for use in patients with moderate or severe hepatic disease. Additionally, because the drug is a fixed-dose tablet whose individual components cannot be adjusted for hepatic function, use of this combination product is not recommended for patients with any degree of hepatic impairment. Zidovudine is primarily eliminated by hepatic metabolism and zidovudine concentrations are increased in patients with impaired hepatic function, which may result in hematologic toxicity. For abacavir, dose reductions are required for patients with mild hepatic impairment (Child-Pugh A), and safe/effective use of the drug has not been established in patients with moderate or severe hepatic disease (Child-Pugh B or C). Risk factors for hepatotoxicity or lactic acidosis during nucleoside analog therapy include alcoholism, obesity, and prolonged nucleoside exposure. Fatalities have been reported with use of antiretroviral agents alone or in combination, including abacavir, lamivudine, and zidovudine. A majority of these cases occurred in females. Treatment should be discontinued in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, which may include hepatomegaly and steatosis even in the absence of marked increases in transaminases.
Perform HBV screening in any patient who presents with HIV-infection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. It should also be noted that following discontinuation of lamivudine in patients with HBV and HIV infection, some patients experienced clinical or laboratory evidence of hepatitis B exacerbation, which has been fatal in some cases. This reaction may be more severe in patients with decompensated hepatic disease. Thus, patients with HBV and HIV should have transaminase concentrations monitored every 6 weeks for the first 3 months after stopping abacavir; lamivudine; zidovudine, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still require treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct hepatitis and HIV coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. Guidelines recommend against the use of the 3-drug regimen abacavir; lamivudine; zidovudine in pregnant patients. Patients who become pregnant while taking abacavir; lamivudine; zidovudine should be switched to an alternative regimen. Available data from the Antiretroviral Pregnancy Registry, which includes first trimester exposures to abacavir (1,455 exposures), lamivudine (5,613 exposures), and zidovudine (4,252 exposures), have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When exposure occurred in the first trimester, prevalence of defects was 3.2% (95% CI: 2.4 to 4.3) for abacavir, 3.1% (95% CI: 2.6 to 3.6) for lamivudine, and 3.2% (95% CI: 2.7 to 3.8) for zidovudine. Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in-utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy itself can mimic some early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant patients receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester of pregnancy and any new symptoms should be evaluated thoroughly. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than or equal to 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years and have CD4 counts less than 300 cells/mm3, patients with inconsistent adherence, or patients with detectable viral loads. For patients on HAART less than 2 years but have CD4 counts greater than or equal to 300 cells/mm3, monitor CD4 counts every 6 months. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of planned delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at deliver. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to abacavir; lamivudine; zidovudine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.
HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission. Advise patients who receive a diagnosis of HIV infection while breast-feeding (acute HIV) to immediately discontinue breast-feeding and switch to replacement feeding in order to reduce the risk of postnatal HIV transmission to the infant. Replacement feeding is also recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). All 3 drug components are excreted into human breast milk. In 1 study conducted in Botswana, the mean breast milk-to-plasma ratio of abacavir was 0.85 in the 15 women tested. Further, an analysis of 9 breast-feeding infants found detectable plasma drug concentrations in 1 infant. In the Swiss Mother and Child HIV Cohort nested study, abacavir was measurable in 4 breast-fed infants; the relative infant dose was 0.34%. Lamivudine was found to be secreted in human breast milk during a study involving 20 breast-feeding women with HIV who were administered either 300 mg of lamivudine twice daily as a single agent (n = 10) or lamivudine 150 mg twice daily in combination with zidovudine (n = 10). The mean breast milk concentrations of lamivudine in the respective groups were similar at 1.22 microgram/mL (range less than 0.5 to 6.09 microgram/mL) and 0.9 microgram/mL (range less than 0.5 to 8.2 microgram/mL). Zidovudine, administered as 300 mg PO twice daily, was found to be secreted in human breast milk during a study involving 18 breast-feeding women with HIV. Data from this study revealed higher median zidovudine concentrations in the breast milk (207 ng/mL) than in the serum of the mothers (58 ng/mL). Other antiretroviral mediations whose passage into human breast milk have been evaluated include nevirapine and nelfinavir.
Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. The prevalence of transmitted drug resistance (TDR) in high-income countries ranges from 9% to 14% and varies by country. In most TDR surveys, non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance are the most common mutation class types detected, followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) resistance mutations, respectively. Resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. Patients with prolonged prior nucleoside reverse transcriptase inhibitor (NRTI) exposure or who had HIV-1 isolates that contain multiple mutations conferring antimicrobial resistance to other NRTIs had limited response to abacavir. The potential for cross-resistance between abacavir, lamivudine, and zidovudine with other antiretroviral drugs should be considered when choosing new therapeutic regimens in previously treated patients.
Monitor patients for signs of myopathy and myositis, as they have been reported, along with pathological changes similar to that produced by HIV, with prolonged use of zidovudine.
Use abacavir; lamivudine; zidovudine cautiously in patients with peripheral neuropathy. Patients with peripheral neuropathy can experience exacerbations during lamivudine therapy.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of HIV treatment, patients whose immune system responds to abacavir; lamivudine; zidovudine therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.
Conflicting data have been published regarding the potential for increased risk of myocardial infarction (MI) in persons receiving treatment with abacavir-containing regimens. Several prospective, observational, epidemiological studies have reported an association with the use of abacavir and the risk of MI. Patients in these studies who started abacavir for the first time had worse initial cardiovascular risk profiles than observed with the other nucleoside reverse transcriptase inhibitor (NRTI) agents; therefore, it can not be ruled out that some of these results could be the result of channeling bias. The authors of these studies speculate that the underlying mechanism for increased risk of CVD may be due to an increased propensity for subclinical atherosclerosis to manifest itself clinically as a consequence of the pro-inflammatory potential of abacavir; however, a biological mechanism to explain the potential increase in risk has not been definitely established. In contrast to the observational trials, a sponsor-conducted, pooled analysis of clinical trials showed no excess risk of MI in abacavir-treated subjects as compared with control subjects. Furthermore, a meta-analysis of 26 randomized clinical trials conducted by the FDA failed to reveal an association between treatment with abacavir-containing regimens and development of MI (OR = 1.02; 95% CI 0.56 to 1.84). As a precaution, the manufacturer of abacavir recommends considering the underlying risk of cardiac disease and taking action to minimize all modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, and smoking) when prescribing antiretroviral therapies, including abacavir. The HIV guidelines recommend consideration be given to avoiding use of abacavir-containing regimens in patients with known high cardiovascular risk.
HIV treatment guidelines recommend all patients presenting with HIV infection undergo routine screening for hepatitis C virus (HCV). For HCV seronegative individuals who are at continued high risk of acquiring hepatitis C, specifically men who have sex with men (MSM) or persons who inject drugs, additional HCV screening is recommended annually or as indicated by clinical presentation (e.g., unexplained ALT elevation), risk activities, or exposure. Similarly, the AASLD/IDSA HCV guidelines and the CDC preexposure prophylaxis (PrEP) guidelines recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and persons who inject drugs. Use an FDA-approved immunoassay licensed for detection of HCV antibodies (anti-HCV); in settings where acute HCV infection is suspected or in persons with known prior infection that cleared spontaneously or after treatment, use of nucleic acid testing for HCV RNA is recommended. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. It is recommended to use a fully suppressive antiretroviral therapy and an HCV regimen in all patients with coinfection regardless of CD4 count, as lower CD4 counts do not appear to compromise the efficacy of HCV treatment. In most patients, a simplified pangenotypic HCV regimen (i.e., glecaprevir; pibrentasvir or sofosbuvir; velpatasvir) may be an appropriate choice; however, these regimens are NOT recommended for use in persons with HCV and HIV coinfection who: are treatment-experience with HCV relapse (reinfection after successful therapy is not an exclusion); have decompensated cirrhosis; on a tenofovir disoproxil fumarate containing regimen with eGFR less than 60 mL/minute; on efavirenz, etravirine, nevirapine, or boosted protease inhibitor; have untreated chronic hepatitis B; are pregnant. Patients with HCV and HIV coinfection who meet these exclusion criteria should be treated for HCV following standard approaches as described in the AASLD/IDSA HCV guidelines. Treatment of HCV infection in children younger than 3 years is not usually recommended; however, treatment should be considered for all children 3 years and older with HCV and HIV coinfection who have no contraindications to treatment. Instruct patients with coinfection to avoid consuming alcohol, limit ingestion of potentially hepatotoxic medications, avoid iron supplementation in the absence of documented iron deficiency, and receive vaccinations against hepatitis A and hepatitis B as appropriate.
In utero exposure to zidovudine-containing products has been associated with mitochondrial toxicity in newborns. Hyperlactatemia can occur after delivery, but it is transient and asymptomatic in most cases. While routine monitoring of serum lactate is not recommended for all newborns, evaluation for a mitochondrial disorder, including serum lactate measurement, should be considered for those newborns who develop clinical symptoms, particularly neurologic symptoms. In symptomatic infants with significantly abnormal lactate concentrations (more than 5 mmol/L), discontinue ARV prophylaxis and consult a pediatric HIV expert. Data are limited concerning potential toxicities in infants whose mothers received combination ARV therapy. More intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised in these infants. Current clinical guidelines recommend long-term follow-up for all children exposed to ARVs in utero. It is recommended that health care providers who are treating the newborns of women with HIV report cases of prenatal ARV exposure to the Antiretroviral Pregnancy Registry (telephone 800-258-4263; fax 800-800-1052); the Antiretroviral Pregnancy Registry is also accessible via the Internet.
HIV guidelines recommend screening for HLA-B*5701 before initiating an abacavir-containing regimen to reduce the risk of hypersensitivity reaction. HLA-B*5701-positive patients should not be prescribed abacavir.
NOTE: HIV guidelines recommend consideration be given to avoiding use of abacavir-containing regimens in patients at high risk for cardiovascular adverse events. Although a definitive correlation has not been established, recent (within 6 months) or current use of abacavir has been associated with an increased risk of myocardial infarction.
Initiation of therapy for HIV treatment:
-For adults, initiation of treatment immediately (or as soon as possible) after HIV diagnosis is recommended in all patients to reduce the risk of disease progression and to prevent the transmission of HIV, including perinatal transmission and transmission to sexual partners. Starting antiretroviral therapy early is particularly important for patients with AIDS-defining conditions, those with acute or recent HIV infection, and individuals who are pregnant; delaying therapy in these subpopulations has been associated with high risks of morbidity, mortality, and HIV transmission.
-Prior to initiating treatment, obtain baseline plasma HIV RNA (viral load) and CD4 count; results do not need to be available before starting therapy.
-Antiretroviral drug-resistance testing:-Genotypic drug-resistance testing is recommended prior to initiation of therapy and prior to changing therapy for treatment failure.
--Standard genotypic drug-resistance testing in treatment-naive people should focus on testing for mutations in reverse transcriptase (RT) and protease (PR) genes.
-Testing for mutations in the integrase gene should also be performed if integrase strand transfer inhibitor (INSTI) resistance is a concern (e.g., people who acquire HIV after pre-exposure prophylaxis with long-acting cabotegravir).
-Phenotypic resistance testing may be used in conjunction with the genotypic test for patients with known or suspected complex drug-resistance mutation patterns.
-HIV-1 proviral DNA resistance testing is available for use in patients with HIV RNA concentrations below the limits of detection or with low-level viremia (i.e., less than 1,000 copies/mL), where genotypic testing is unlikely to be successful; however, the clinical utility of this assay has not been fully determined.
-It is not necessary to delay treatment until resistance test results are available; however, subsequent modifications to the treatment regimen should be made, if needed, once the test results are available.
-Pediatric guidelines are also available.
Place in therapy for HIV treatment:
-Not recommended as initial therapy. Abacavir; lamivudine; zidovudine (i.e., triple NRTI regimen) and abacavir; lamivudine; zidovudine plus tenofovir disoproxil fumarate (i.e., quadruple NRTI regimen) are inferior to efavirenz- or PI-containing regimens. Virologic failure occurs sooner and more frequently in patients receiving abacavir; lamivudine; zidovudine alone, regardless of baseline viral load.
-Pediatric guidelines are also available.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: human immunodeficiency virus (HIV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of human immunodeficiency virus (HIV) infection:
Oral dosage:
Adults: 1 tablet (abacavir 300 mg; lamivudine 150 mg; zidovudine 300 mg) PO twice daily.
Children and Adolescents weighing 40 kg or more: 1 tablet (abacavir 300 mg; lamivudine 150 mg; zidovudine 300 mg) PO twice daily.
Maximum Dosage Limits:
-Adults
Abacavir 600 mg/day; lamivudine 300 mg/day; zidovudine 600 mg/day.
-Geriatric
Abacavir 600 mg/day; lamivudine 300 mg/day; zidovudine 600 mg/day.
-Adolescents
weight 40 kg or more: Abacavir 600 mg/day; lamivudine 300 mg/day; zidovudine 600 mg/day.
weight less than 40 kg: Safety and efficacy have not been established.
-Children
weight 40 kg or more: Abacavir 600 mg/day; lamivudine 300 mg/day; zidovudine 600 mg/day.
weight less than 40 kg: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
The fixed-dose combination of abacavir; lamivudine; zidovudine is not recommended for use in patients with impaired hepatic function (Child-Pugh A, B, or C).
Patients with Renal Impairment Dosing
CrCl 50 mL/minutes or more: No dosage adjustment is needed.
CrCl less than 50 mL/minute: Not recommended.
*non-FDA-approved indication
Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Aspirin: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Codeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Diphenhydramine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Hydrocodone: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Ibuprofen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Oxycodone: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Adefovir: (Major) Patients who are concurrently taking adefovir with antiretrovirals (i.e., anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs)) are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Alogliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Amiloride: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Amphotericin B lipid complex (ABLC): (Moderate) The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.
Aspirin, ASA; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Atovaquone: (Minor) Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine. Inhibition of zidovudine metabolism by atovaquone could result in an increase in zidovudine-induced adverse effects.
Atovaquone; Proguanil: (Minor) Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine. Inhibition of zidovudine metabolism by atovaquone could result in an increase in zidovudine-induced adverse effects.
Azathioprine: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive, such as azathioprine. A significant toxicity of zidovudine, ZDV is myelosuppression and resulting neutropenia and anemia.
Benzhydrocodone; Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like lamivudine; the risk of peripheral neuropathy may be additive. (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like zidovudine; the risk of peripheral neuropathy may be additive.
Butalbital; Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Butalbital; Acetaminophen; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Butalbital; Acetaminophen; Caffeine; Codeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with abacavir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and abacavir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Canagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Cidofovir: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine.
Clarithromycin: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Clofarabine: (Moderate) Concomitant use of clofarabine and zidovudine, ZDV may result in altered clofarabine levels because both agents are substrates of OAT1 and OAT3. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 substrates.
Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with zidovudine is necessary as there is an increased risk of hematologic toxicity and immunosuppression.
Dapagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Dapsone: (Minor) Zidovudine, ZDV should be given with caution to patients also receiving dapsone due to the risk of additive hematologic toxicity.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Dofetilide: (Moderate) Drugs that are actively secreted via cationic secretion, such as lamivudine, should be co-administered with dofetilide with caution since they could increase dofetilide plasma concentrations via potential competition for renal tubular secretion.
Donepezil; Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
Doxorubicin Liposomal: (Major) Avoid concomitant administration of zidovudine, ZDV, and doxorubicin as an antagonistic relationship has been demonstrated in vitro.
Doxorubicin: (Major) Avoid concomitant administration of zidovudine, ZDV, and doxorubicin as an antagonistic relationship has been demonstrated in vitro.
Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, more study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Empagliflozin; Linagliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Empagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Emtricitabine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Ertugliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking abacavir. Abacavir is metabolized via alcohol dehydrogenase. Alcohol decreases the elimination of abacavir causing an increase in overall exposure to abacavir. In a study involving HIV-infected men, coadministration of alcohol and abacavir resulted in a 41% increase in abacavir AUC and a 26% increase in abacavir half-life. In males, abacavir had no effect on the pharmacokinetic properties of alcohol; this interaction has not been studied in females. Abacavir has no effect on the pharmacokinetic properties of alcohol. (Major) Because abacavir is metabolized via alcohol dehydrogenase, alcohol decreases the elimination of abacavir causing an increase in overall exposure to abacavir. In a study involving HIV-infected men, coadministration of alcohol and abacavir resulted in a 41% increase in abacavir AUC and a 26% increase in abacavir half-life. In males, abacavir had no effect on the pharmacokinetic properties of alcohol; this interaction has not been studied in females. Abacavir has no effect on the pharmacokinetic properties of alcohol.
Fluconazole: (Minor) During concomitant administration with fluconazole, the clearance of zidovudine may be reduced. Although the clinical significance of this interaction has not been established, patients receiving fluconazole with zidovudine should be closely monitored for zidovudine-induced adverse effects, especially hematologic toxicity. Zidovudine dosage reduction may be considered.
Flucytosine: (Moderate) Zidovudine, ZDV should be used cautiously with other drugs that can cause bone marrow suppression, such as flucytosine, because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage of zidovudine may be warranted.
Foscarnet: (Minor) Concurrent use of foscarnet and zidovudine, ZDV may be associated with a higher incidence of anemia; clinicians should follow normal recommendations for blood count monitoring and other parameters.
Fosphenytoin: (Minor) Coadministration with zidovudine may result in either increased or decreased phenytoin concentrations.
Ganciclovir: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.
Glipizide; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Glyburide; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Indinavir: (Moderate) When indinavir and zidovudine, ZDV were administered concurrently, the AUC of indinavir and zidovudine was increased by 13% +/- 48% and 17% +/- 23%, respectively. Dosage adjustments are not recommended when zidovudine is administered with indinavir.
Interferon Alfa-2b: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Alfa-n3: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Beta-1a: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Beta-1b: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Gamma-1b: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferons: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
Isoniazid, INH; Rifampin: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Leflunomide: (Moderate) Closely monitor for zidovudine-induced side effects such as hematologic toxicity when these drugs are used together. In some patients, a dosage reduction of zidovudine may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with zidovudine, a substrate of OAT3, may increase zidovudine plasma concentrations.
Linagliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Lopinavir; Ritonavir: (Moderate) Caution is advised when administering abacavir and ritonavir concurrently. Ritonavir appears to induce glucuronosyl transferase, and therefore, has the potential to reduce plasma concentrations of drugs that undergo glucuronidation, such as abacavir. The clinical significance of the potential for this interaction is unknown. (Minor) Since ritonavir induces glucuronidation, there is the potential for reduction in zidovudine, ZDV plasma concentrations during concurrent therapy with ritonavir. When coadministered with ritonavir, the AUC and Cmax of zidovudine, ZDV are decreased by 12% and 27%. The clinical significance of this interaction is unknown.
Mafenide: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Repaglinide: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Saxagliptin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Sitagliptin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Methadone: (Moderate) In a study of 11 adult HIV-infected subjects receiving methadone maintenance therapy (40 to 90 mg/day) and abacavir 600 mg twice daily (twice the current recommended dose), methadone clearance increased by 22% (6% to 42%). While this interaction will not require dosage adjustment in the majority of patients, a small number of patients may require increased doses of methadone. In addition, a significant decrease in abacavir Cmax (34%) and increase in Tmax (67%) were noted, but no changes in overall abacavir clearance or half-life were reported. The clinical significance regarding abacavir therapy is not known. (Moderate) Methadone increases exposure zidovudine, ZDV. Patients should be monitored for zidovudine toxicity during concurrent methadone treatment; however, the manufacturer of zidovudine states that routine dosage adjustment of zidovudine is not required during coadministration of methadone. Patients who receive both methadone and zidovudine may experience symptoms characteristic of opiate withdrawal and attribute the cause to decreased methadone levels due to zidovudine. However, it is more likely patients are actually experiencing zidovudine side effects due to increased levels since zidovudine has no effect on methadone metabolism. In one pharmacokinetic study (n=9), coadministration of methadone increased the AUC of zidovudine by about 43% (range: 16-64%). It appears methadone inhibits zidovudine glucuronidation and, to a lesser extent, decreases zidovudine renal clearance.
Nirmatrelvir; Ritonavir: (Moderate) Caution is advised when administering abacavir and ritonavir concurrently. Ritonavir appears to induce glucuronosyl transferase, and therefore, has the potential to reduce plasma concentrations of drugs that undergo glucuronidation, such as abacavir. The clinical significance of the potential for this interaction is unknown. (Minor) Since ritonavir induces glucuronidation, there is the potential for reduction in zidovudine, ZDV plasma concentrations during concurrent therapy with ritonavir. When coadministered with ritonavir, the AUC and Cmax of zidovudine, ZDV are decreased by 12% and 27%. The clinical significance of this interaction is unknown.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Rifabutin may accelerate the metabolism of zidovudine. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required. The CDC currently considers the nucleoside reverse transcriptase inhibitors, including zidovudine, compatible for concomitant use with rifamycins, including rifampin, rifabutin and rifapentine.
Orlistat: (Moderate) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
Peginterferon Alfa-2a: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Peginterferon Alfa-2b: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Peginterferon beta-1a: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Phenytoin: (Minor) Coadministration with zidovudine has resulted in altered phenytoin concentrations. Reports have varied, with increased and decreased phenytoin concentrations being reported. Use combination with caution.
Pioglitazone; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Probenecid: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Probenecid; Colchicine: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Procainamide: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
Pyrimethamine: (Major) Pyrimethamine should be used cautiously with zidovudine, ZDV because of the potential for the development of blood dyscrasias including megaloblastic anemia, agranulocytosis, or thrombocytopenia. Monitor CBCs routinely in patients receiving both drugs simultaneously; if signs of folate deficiency develop, pyrimethamine should be discontinued.
Ribavirin: (Moderate) Use abacavir with ribavirin and interferon with caution and closely monitor for hepatic decompensation and anemia. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Hepatic decompensation (some fatal) has occurred in HCV/HIV coinfected patients who received both ribavirin/interferon and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) therapies. (Moderate) Use lamivudine with ribavirin and interferon with caution and closely monitor for hepatic decompensation and anemia. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Hepatic decompensation (some fatal) has occurred in HCV/HIV coinfected patients who received both ribavirin/interferon and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) therapies. In addition, ribavirin has been shown in cell culture to inhibit phosphorylation of lamivudine, which could lead to decreased antiretroviral activity; however, while ribavirin inhibits the phosphorylation reactions required to activate lamivudine, no evidence of a pharmacokinetic or pharmacodynamic interaction has been observed. (Moderate) Use zidovudine with ribavirin and interferon with caution and closely monitor for hepatic decompensation and anemia. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Hepatic decompensation (some fatal) has occurred in HCV/HIV coinfected patients who received both ribavirin/interferon and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) therapies. In addition, ribavirin may antagonize the cell culture antiviral activity of zidovudine against HIV; however, no evidence of a pharmacokinetic or pharmacodynamic interaction has been observed.
Rifabutin: (Minor) Rifabutin may accelerate the metabolism of zidovudine. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required. The CDC currently considers the nucleoside reverse transcriptase inhibitors, including zidovudine, compatible for concomitant use with rifamycins, including rifampin, rifabutin and rifapentine.
Rifampin: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
Rifapentine: (Minor) Rifapentine appears to increase the glucuronidation of zidovudine, ZDV similar to other rifamycins. This may cause a decrease in zidovudine AUC. However, the effectiveness of zidovudine against HIV does not appear to be altered. The activity of zidovudine is dependent on the intracellular concentration of the triphosphate metabolite which is not correlated with plasma concentrations of the parent compound. The CDC currently considers the nucleoside reverse transcriptase inhibitors (NRTIs), including zidovudine, compatible for concomitant use with rifamycins (including rifampin, rifabutin and rifapentine). No dosing adjustments are necessary.
Riociguat: (Moderate) Monitor for an increase in riociguat-related adverse effects like hypotension if concomitant use with abacavir is necessary. Consider a riociguat dose reduction in patients who may not tolerate the hypotensive effect of riociguat. Concomitant use of riociguat and abacavir may increase riociguat exposure although the magnitude of increase is unknown. Riociguat is a CYP1A1 substrate; abacavir may inhibit CYP1A1.
Ritonavir: (Moderate) Caution is advised when administering abacavir and ritonavir concurrently. Ritonavir appears to induce glucuronosyl transferase, and therefore, has the potential to reduce plasma concentrations of drugs that undergo glucuronidation, such as abacavir. The clinical significance of the potential for this interaction is unknown. (Minor) Since ritonavir induces glucuronidation, there is the potential for reduction in zidovudine, ZDV plasma concentrations during concurrent therapy with ritonavir. When coadministered with ritonavir, the AUC and Cmax of zidovudine, ZDV are decreased by 12% and 27%. The clinical significance of this interaction is unknown.
Ropeginterferon alfa-2b: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Sorbitol: (Major) Avoid coadministration of lamivudine oral solution and sorbitol if possible due to sorbitol dose-dependent reduction in lamivudine exposure. An all-tablet regimen should be used when possible to avoid a potential interaction with sorbitol. Consider more frequent monitoring of viral load when treating with lamivudine oral solution. In a drug interaction study in 16 healthy adult patients, coadministration of a single 300 mg dose of lamivudine oral solution with sorbitol 3.2 g, 10.2 g, or 13.4 g resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC24 and 28%, 52%, and 55% in the Cmax of lamivudine.
Stavudine, d4T: (Contraindicated) Zidovudine, ZDV, may competitively inhibit the intracellular phosphorylation of stavudine, d4T. Therefore, use of these drugs together is not recommended. At a molar ratio of 20:1 (stavudine:zidovudine), an antagonistic antiviral effect was detected, while at molar ratios of 100:1 and 500:1, antiviral effects were additive. Administration of zidovudine is recommended during labor and delivery in HIV-infected women; for women who are receiving a stavudine-containing regimen, discontinue stavudine during labor while intravenous zidovudine is being administered. Following delivery, the previous anti-retroviral regimen can be resumed.
Sulfadiazine: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use. (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Sulfasalazine: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Sulfonamides: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Teriflunomide: (Major) Zidovudine, ZDV should be used cautiously with other drugs that can cause bone marrow suppression including teriflunomide because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage or discontinuation of zidovudine may be warranted. Teriflunomide, an organic anion transporter OAT3 renal updake inhibitor, may cause elevated concentrations of zidovudine, an OAT3 substrate.
Tipranavir: (Moderate) Concurrent administration of tipranavir and ritonavir with abacavir results in decreased abacavir concentrations. The clinical significance of this interaction has not been established, and no recommendations for abacavir dosage adjustments are available. (Moderate) Concurrent administration of tipranavir and ritonavir with zidovudine results in decreased zidovudine concentrations. The clinical significance of this interaction has not been established, and no recommendations for zidovudine dosage adjustments are available.
Tramadol; Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Trimethoprim: (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Trospium: (Moderate) Trospium is eliminated by active tubular secretion and has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion including lamivudine. In theory, coadministration of trospium with lamivudine may increase the serum concentrations of trospium or lamivudine due to competition for the drug elimination pathway.
Valganciclovir: (Major) Zidovudine should be used cautiously with other drugs that can cause bone marrow suppression, such as valganciclovir, because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage of zidovudine may be warranted. Occasionally, discontinuation of therapy or the addition of a hematopoietic colony stimulating factor may be necessary.
Valproic Acid, Divalproex Sodium: (Minor) Concomitant administration of valproic acid and oral zidovudine may result in increase in the area under the concentration-time curve of zidovudine and a decrease in the AUC of its glucuronide metabolite. This interaction does not appear to be clinically significant unless the patient is experiencing hematologic toxicities. The dose of zidovudine may be reduced in patients who are experiencing pronounced anemia while receiving chronic coadministration of zidovudine and valproic acid.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Voriconazole: (Minor) Concomitant administration of voriconazole and zidovudine may result in a reduction in the clearance of zidovudine.
Abacavir, lamivudine, and zidovudine inhibit viral reverse transcriptase. The relationship between in vitro susceptibility of HIV to abacavir, lamivudine, or zidovudine and the inhibition of HIV replication in humans has not been established. Resistance to 1 nucleoside reverse transcriptase inhibitor does not confer resistance to the entire class.
Abacavir: Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, an analog of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3'-hydroxyl group in the incorporated nucleoside analog prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is inhibited.
Abacavir hypersensitivity may be related to an induced autoimmunity process related to HLA-B*5701. Human Leukocyte Antigens (HLAs) help the body to distinguish "self" versus "foreign" proteins (peptides). A study determined that abacavir alters the quantity and quality of self-peptide loading into HLA-B*5701. These self-peptides are then presented for the first time and because the body has not previously recognized them, it mistakenly treats them as foreign, resulting in a polyclonal T-cell autoimmune response and multi-organ systemic toxicity. Once the drug is discontinued, reactive T-cells would be reduced and then differentiate into T memory cells. Re-exposure would again generate these peptides leading to a rapid expansion of T memory cells which could cause severe and potentially life-threatening reactions.
Lamivudine: The in vitro activity of lamivudine has been assessed in a number of cell lines where lamivudine showed anti-HIV activity in all virus-cell infections tested. Intracellular phosphorylation of lamivudine produces the 5'-triphosphate metabolite (L-TP) in vitro. This active metabolite inhibits reverse transcriptase and viral DNA synthesis. L-TP also inhibits cellular DNA polymerase. Combination therapy targets different points in the life cycle of HIV, reducing the ability of HIV to mutate to drug-resistant strains.
Zidovudine: Zidovudine activity is dependent upon intracellular conversion to zidovudine 5'-triphosphate (ZDV-TP); the rate of phosphorylation varies depending on cell type. ZDV-TP inhibits the activity of the HIV reverse transcriptase by both competing for utilization with the natural substrate, deoxythymidine 5'-triphosphate (dTTP), and by incorporation into viral DNA. The lack of a 3'-OH group in the incorporated nucleoside analog prevents the formation of 5' to 3' phosphodiester linkage essential for DNA chain elongation, and, therefore, viral DNA growth is terminated and production of new virions is inhibited. The active metabolite is also a weak inhibitor of cellular DNA polymerase-alpha and mitochondrial polymerase-gamma and has been reported to be incorporated into DNA cells in vitro.
Abacavir; lamivudine; zidovudine is administered orally.
-Abacavir: Once in the systemic circulation, abacavir distributes into extravascular space. In humans, cytochrome P450 enzymes do not significantly metabolize abacavir. The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase (to form the 5'-carboxylic acid) and glucuronyl transferase (to form the 5'glucuronide). The metabolites have no antiviral activity. Abacavir metabolites are primarily eliminated in the urine. Fecal elimination accounted for 16% of the dose. In single-dose studies, the observed elimination half-life ranges in patients with normal renal function from 0.91 to 2.17 hours.
-Lamivudine: Hepatic metabolism is a minor route of elimination for lamivudine. The only known metabolite of lamivudine in humans is the trans-sulfoxide metabolite, which accounts for less than 5% of a dose appearing in the urine. The mean elimination half-life with normal renal function after a single dose of lamivudine ranges 5 to 7 hours. Total clearance of lamivudine decreases as creatinine clearance decreases.
-Zidovudine: Metabolism of zidovudine the major metabolite 3'-azido-3'-deoxy-5'-O-beta-D-glucopyranuronosylthymidine (GZDV) occurs in the liver. A second metabolite has been identified in the plasma. Glomerular filtration and tubular secretion excrete both the active drug and metabolites. Zidovudine half-life is about 1 hour in patients with normal renal function.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A1, CYP3A4
Data from in vitro studies show abacavir has the potential to inhibit CYP1A1 and the limited potential to inhibit CYP3A4. Other CYP isoenzymes (e.g., CYP2C9 and CYP2D6) are not inhibited or induced by abacavir. Similarly, abacavir at therapeutic drug exposures is not expected to affect the pharmacokinetics of substrates of the following drug transporters: organic anion transporter polypeptide (OATP)1B1/3, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic cation transporter (OCT)1, OCT2, or multidrug and toxic extrusion protein (MATE)1 and MATE2-K.
-Route-Specific Pharmacokinetics
Oral Route
In a single-dose, 3-way crossover study in healthy volunteers, 1 Trizivir tablet was bioequivalent to one 300 mg abacavir tablet, one 150 mg lamivudine tablet, plus one 300 mg zidovudine tablet. Administration of abacavir; lamivudine; zidovudine with food did not alter the extent of abacavir, lamivudine, or zidovudine absorption (AUC) as compared to fasted conditions.
-Lamivudine: Following oral administration, lamivudine is rapidly and extensively distributed. Most of an oral dose of lamivudine (71%) is excreted unchanged in the urine.
-Zidovudine: Zidovudine is rapidly absorbed and extensively distributed following oral administration.
-Special Populations
Hepatic Impairment
-Zidovudine: Hepatic dysfunction causes a moderate prolongation of zidovudine half-life.
Renal Impairment
-Zidovudine: Zidovudine's half-life increases to about 1.4 to 2.9 hours in patients with renal dysfunction.
Other
Pregnancy
-Abacavir: A population pharmacokinetic analysis of 266 samples from 36 pregnant and 114 non-pregnant females, found the pharmacokinetic parameters of abacavir to be unchanged during pregnancy. Similarly, 1 pharmacokinetic study found abacavir exposure in 25 pregnant women receiving 300 mg twice daily during the third trimester to be comparable to exposures observed in postpartum women and historical controls of non-pregnant patients with HIV. Abacavir crosses the placenta via passive diffusion, with drug concentrations in neonatal plasma cord samples at birth being essentially equal to those in the maternal plasma at the time of delivery.
-Lamivudine: Although population pharmacokinetic modeling suggests the oral clearance of lamivudine is increased by 22% during pregnancy, limited data from 2 studies involving 36 pregnant women (16 at 36 weeks, 20 at 38 weeks gestation) found the pharmacokinetic parameters of lamivudine to be similar to those observed in non-pregnant and postpartum adults. No change in dose is indicated. In addition, placental transfer of lamivudine results in drug concentrations that are 2 times greater than maternal serum levels.
-Zidovudine: Zidovudine pharmacokinetics are not significantly altered during pregnancy, and no change in dose is indicated. There is high placental transfer to the fetus.