Version May 2024
Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir, a component of abacavir/lamivudine.
Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry HLA-B*5701 allele.
Abacavir is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701–positive patients. All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir/lamivudine or reinitiation of therapy with abacavir/lamivudine, unless patients have a previously documented HLA-B*5701 allele assessment. Discontinue abacavir/lamivudine immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible.
Following a hypersensitivity reaction to abacavir/lamivudine, never restart abacavir/lamivudine or any abacavir-containing product because more severe symptoms, including death, can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity.
Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine, which is a component of abacavir/lamivudine. Hepatic function should be closely monitored with both clinical and laboratory follow-up for at least several months in patients who discontinue abacavir/lamivudine and are coinfected with HIV-1 and HBV. If appropriate, initiation of antihepatitis B therapy may be warranted.
HIV-1 infection, treatment: Oral: 1 tablet (abacavir 600 mg and lamivudine 300 mg) once daily as part of an appropriate combination regimen. Note: Abacavir and lamivudine should not be used in combination with efavirenz, raltegravir, boosted atazanavir, or boosted darunavir in patients with pretreatment HIV RNA ≥100,000 copies/mL (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl ≥30 to <50 mL/minute: No dosage adjustment necessary; monitor for hematologic toxicities.
CrCl <30 mL/minute: Use is not recommended (use dose-adjusted individual components).
Mild impairment (Child-Pugh class A): Use is not recommended (use dose-adjusted individual components).
Moderate and severe impairment (Child-Pugh class B or C): Use is contraindicated.
(For additional information see "Abacavir and lamivudine: Pediatric drug information")
Dosage guidance:
Clinical considerations: Use in combination with other antiretroviral agents; evaluate gene mutation and antiretroviral resistance patterns (refer to www.IASUSA.org and https://hivdb.stanford.edu/ for more information).
HIV-1 infection, treatment:
Tablet for oral suspension: Abacavir 60 mg/lamivudine 30 mg per tablet:
Infants ≥3 months weighing ≥5 kg, Children, and Adolescents:
Once-daily dosing: Abacavir 60 mg/lamivudine 30 mg per tablet:
Note: Fixed doses target a weight-based dose of abacavir 16 mg/kg/dose and lamivudine 8 mg/kg/dose administered once daily.
5 to <6 kg: Oral: 1.5 tablets once daily.
6 to <9 kg: Oral: 2 tablets once daily.
9 to <12 kg: Oral: 3 tablets once daily.
12 to <17 kg: Oral: 4 tablets once daily.
17 to <20 kg: Oral: 5 tablets once daily.
20 to <25 kg: Oral: 6 tablets once daily.
25 to <29 kg: Oral: 7 tablets once daily.
29 to <35 kg: Oral: 8 tablets once daily.
≥35 kg: Oral: 10 tablets once daily.
Twice-daily dosing: Abacavir 60 mg/lamivudine 30 mg per tablet:
Note: Fixed doses target a weight-based dose of abacavir 8 mg/kg/dose and lamivudine 4 mg/kg/dose administered twice daily.
5 to <6 kg: Oral: 0.5 tablet in the morning, and 1 tablet in the evening.
6 to <9 kg: Oral: 1 tablet in the morning, and 1 tablet in the evening.
9 to <12 kg: Oral: 1.5 tablets in the morning, and 1.5 tablets in the evening.
12 to <17 kg: Oral: 2 tablets in the morning, and 2 tablets in the evening.
17 to <20 kg: Oral: 2.5 tablets in the morning, and 2.5 tablets in the evening.
20 to <25 kg: Oral: 3 tablets in the morning, and 3 tablets in the evening.
25 to <29 kg: Oral: 3.5 tablets in the morning, and 3.5 tablets in the evening.
29 to <35 kg: Oral: 4 tablets in the morning, and 4 tablets in the evening.
≥35 kg: Oral: 5 tablets in the morning, and 5 tablets in the evening.
Tablet: Abacavir 600 mg/lamivudine 300 mg per tablet: Children and Adolescents weighing ≥25 kg: Oral: 1 tablet once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Infants ≥3 months, Children, and Adolescents:
CrCl ≥50 mL/minute/1.73 m2: No dosage adjustment necessary.
CrCl ≥30 to <50 mL/minute/1.73 m2: No dosage adjustment necessary; monitor for hematologic toxicities.
CrCl <30 mL/minute/1.73 m2: Use of combination product not recommended; see individual agents.
Infants ≥3 months, Children, and Adolescents:
Mild impairment: Use of combination product not recommended; see individual agents.
Moderate to severe impairment: Use of combination product is contraindicated; see individual agents.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. See individual agents as well as other combination products for additional information. Rates of adverse reactions were defined during combination therapy with other antiretrovirals.
1% to 10%:
Central nervous system: Abnormal dreams, anxiety, depression, dizziness, fatigue, headache, insomnia, malaise, migraine, vertigo
Dermatologic: Skin rash
Gastrointestinal: Abdominal pain, diarrhea, gastritis
Hypersensitivity: Hypersensitivity (including multiorgan failure and anaphylaxis; ≤9%; higher incidence in subjects carrying the HLA-B*5701 allele)
Miscellaneous: Fever
<1%, postmarketing, and/or case reports: Abnormal breath sounds, alopecia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), aplastic anemia, erythema multiforme, exacerbation of hepatitis B, hepatitis, hyperglycemia, immune reconstitution syndrome, increased creatine phosphokinase, lactic acidosis, liver steatosis, lymphadenopathy, myasthenia, paresthesia, peripheral neuropathy, redistribution of body fat, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, weakness, wheezing
Hypersensitivity to abacavir, lamivudine, or any component of the formulation; patients who have the HLA-B*5701 allele; moderate or severe hepatic impairment
Canadian labeling: Additional contraindications (not in US labeling): Hepatic impairment (regardless of severity)
Concerns related to adverse effects:
• Hypersensitivity reactions: [US Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of abacavir/lamivudine. Patients who carry the HLA-B*5701 allele are at a higher risk for a hypersensitivity reaction to abacavir, although hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele. All patients should be screened for the HLA-B*5701 allele prior to initiating or reinitiation of therapy unless patients have had a previously documented HLA-B*5701 allele assessment. Discontinue abacavir/lamivudine if a hypersensitivity reaction is suspected. Abacavir is contraindicated in patients who have the HLA-B*5701 allele or in patients with a prior hypersensitivity reaction to abacavir. Reintroduction of any abacavir-containing product can result in life-threatening or fatal hypersensitivity reactions, even in patients who have no history of hypersensitivity to abacavir therapy. Such reactions can occur within hours. An allergy to abacavir should be documented in the medical record of allele-positive patients. Reactions usually occur within 9 days of starting abacavir; ~90% occur within 6 weeks, although these reactions may occur at any time during therapy (HHS [adult] 2019). These reactions usually include signs or symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting). Other signs and symptoms include lethargy, headache, myalgia, edema, abnormal chest x-ray findings, arthralgia and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with hypersensitivity reactions. Physical findings (lymphadenopathy, mucous membrane lesions, and rash [maculopapular, urticarial or variable]) may occur. Erythema multiforme has also been reported. Laboratory abnormalities (eg, elevated liver function tests, elevated creatine phosphokinase, elevated creatinine, and lymphopenia) may occur. Abacavir/lamivudine should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Abacavir/lamivudine SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. If abacavir/lamivudine is restarted following an interruption in therapy not associated with symptoms of a hypersensitivity reaction, carefully evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. If abacavir/lamivudine is restarted, continually monitor for symptoms of a hypersensitivity reaction. Make the patient aware that reintroduction should only take place if medical care is readily accessible.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Female gender and obesity may increase the risk for development. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns:
• Coronary heart disease: Use has been associated with an increased risk of MI in some cohort studies (Elion 2018; HHS [adult] 2019). Consider using with caution in patients with risks for coronary heart disease and minimizing modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking) prior to use.
• Chronic hepatitis B: [US Boxed Warning]: Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine, which is 1 component of abacavir/lamivudine. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. Lamivudine-resistant HBV variants have been reported in coinfected patients using lamivudine as part of an antiretroviral regimen.
• Hepatic impairment: Due to fixed dose of combination product, use is not recommended with mild hepatic impairment; use in patients with moderate or severe hepatic impairment is contraindicated.
• Renal impairment: Due to fixed dose of combination product, use is not recommended with renal impairment (CrCl <30 mL/minute).
Concurrent drug therapy issues:
• Duplicate therapy: Concomitant use of other abacavir or lamivudine-containing products with the fixed dose combination product should be avoided.
• Emtricitabine: Concomitant use of emtricitabine-containing products should be avoided.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Abacavir may cause mild hyperglycemia; more common in pediatric patients.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis, which was reported in 14% of patients in 1 open-label, uncontrolled trial; discontinue lamivudine therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. Use with extreme caution and only if there is no satisfactory alternative therapy in pediatric patients with a history of pancreatitis or other significant risk factors for the development of pancreatitis.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults, including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Abacavir and lamivudine tablets for oral suspension: FDA approved December 2023; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Abacavir and lamivudine tablets for oral suspension are indicated for the treatment of HIV-1 infection in pediatric patients ≥3 months of age and weighing ≥5 kg.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Epzicom: Abacavir 600 mg and lamivudine 300 mg [DSC] [contains fd&c yellow #6 (sunset yellow)]
Generic: Abacavir 600 mg and lamivudine 300 mg
Yes
Tablets (Abacavir Sulfate-lamiVUDine Oral)
600-300 mg (per each): $46.50
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Kivexa: Abacavir 600 mg and lamivudine 300 mg [contains fd&c yellow #6 (sunset yellow)]
Generic: Abacavir 600 mg and lamivudine 300 mg
Oral: May be administered with or without food.
Oral: May be administered with or without food.
Tablet for oral suspension: Do not chew. May be swallowed whole or broken in half and swallowed, or may be dispersed in water for administration.
For dispersion in water: Each dose should be prepared just prior to administration; the amount of water used depends on number of tablets needed for dose. Place the appropriate number of tablets in a container; add 10 mL of drinking water per tablet and 5 mL for each 1/2 tablet. Swirl the container or stir with a spoon until the tablets are broken up into small enough pieces to be swallowed, ~2 to 3 minutes; if needed, crush the tablet pieces with a spoon. Administer immediately; if not administered immediately, may be administered within an hour of mixing, but must be stirred or swirled again (~2 to 3 minutes) prior to administration. Discard if not administered within 1 hour. Rinse the container with volume of water similar to initial quantity (eg, ~5 to 10 mL of water per tablet) and administer to ensure entire dosage is received.
Hazardous agent (NIOSH 2016 [group 2]).
Abacavir is a hazardous agent. Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021652s028lbl.pdf#page=27, must be dispensed with this medication. A Warning Card (summarizing symptoms of hypersensitivity), which is available with the product information, must also be dispensed with this medication for each new outpatient prescription and refill.
HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretroviral agents.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
Erdafitinib: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Consider alternatives to this combination when possible. If combined, monitor for increased effects/toxicities of OCT2 substrates and consider OCT2 substrate dose reductions when appropriate. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with MATE1/2-K substrates when possible. If combined, monitor for increased MATE1/2-K substrate toxicities. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with OCT2 substrates when possible. If combined, monitor for increased OCT2 substrate toxicities. Risk D: Consider therapy modification
Foslevodopa: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Levomethadone: May diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Methadone: May diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Methadone. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Riociguat: Abacavir may increase the serum concentration of Riociguat. Risk C: Monitor therapy
Risdiplam: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. Risk D: Consider therapy modification
Sorbitol: May decrease the serum concentration of LamiVUDine. Management: When possible, avoid chronic coadministration of sorbitol-containing solutions with lamivudine, but if this combination cannot be avoided, monitor patients more closely for possible therapeutic failure associated with decreased lamivudine exposure. Risk D: Consider therapy modification
Tafenoquine: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider therapy modification
Tafenoquine: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Risk D: Consider therapy modification
Trimethoprim: May increase the serum concentration of LamiVUDine. Risk C: Monitor therapy
The Health and Human Services (HHS) perinatal HIV guidelines consider abacavir in combination with lamivudine to be a preferred nucleoside reverse transcriptase inhibitor combination for patients with HIV who are not yet pregnant but are trying to conceive; HLA-B*5701 allele status should be evaluated and documented as negative prior to use (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
HLA-B*5701 allele status should be evaluated and documented as negative prior to use; abacavir is contraindicated in all patients who are positive for the HLA-B*5701 allele, including patients who are pregnant.
The Health and Human Services (HHS) perinatal HIV guidelines consider abacavir in combination with lamivudine to be a preferred nucleoside reverse transcriptase inhibitor combination for pregnant patients with HIV who are antiretroviral naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking abacavir/lamivudine may continue if viral suppression is effective and the regimen is well tolerated. This backbone is not recommended with atazanavir/ritonavir or efavirenz if pretreatment HIV RNA is >100,000 copies/mL (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
Abacavir and lamivudine are present in breast milk.
Refer to individual monographs for additional information.
Bilirubin, blood glucose, liver enzymes, hematologic parameters, fasting lipid panel, viral load, and CD4 count; amylase, serum creatine kinase (as clinically indicated); HLA-B*5701 genotype status prior to initiation of therapy; signs and symptoms of hypersensitivity.
Nucleoside reverse transcriptase inhibitor combination.
Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.
One Epzicom tablet is bioequivalent, in the extent (AUC) of absorption and peak concentration, to two abacavir 300 mg tablets and two lamivudine 150 mg tablets.
When abacavir and lamivudine tablets for oral suspension were administered to adult volunteers, abacavir and lamivudine exposures were comparable to those achieved using separate oral solutions.
See individual agents.
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