Abacavir, lamivudine, and zidovudine

Name: Abacavir, lamivudine, and zidovudine

What should I avoid while taking this medicine?

Avoid drinking alcohol. It may increase your risk of liver damage.

Taking this medicine will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Abacavir, lamivudine, and zidovudine dosing information

Usual Adult Dose for HIV Infection:

1 tablet orally twice a day

Use: In combination with other antiretroviral agents or alone, for the treatment of HIV-1 infection

Usual Adult Dose for Nonoccupational Exposure:

US CDC recommendations: 1 tablet orally twice a day
Duration of therapy: 28 days

Comments:
-Recommended as an alternative regimen for nonoccupational postexposure prophylaxis of HIV infection; this triple NRTI regimen is recommended only when a NNRTI-based or a protease inhibitor-based regimen cannot or should not be used.
-Prophylaxis should be started as soon as possible, within 72 hours of exposure.
-Current guidelines should be consulted for additional information.

Usual Adult Dose for Occupational Exposure:

US Public Health Service working group recommendations: 1 tablet orally twice a day
Duration of therapy: 28 days, if tolerated

Comments:
-Only with expert consultation, as an alternative regimen for use as HIV postexposure prophylaxis
-Prophylaxis should be started as soon as possible, preferably within hours after exposure.
-The optimal duration of prophylaxis is unknown and may differ based on institution protocol.
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose for HIV Infection:

At least 40 kg: 1 tablet orally twice a day

Comments: Use of the individual components is recommended for patients less than 40 kg; the manufacturer product information for abacavir, lamivudine, and zidovudine should be consulted.

Use: In combination with other antiretroviral agents or alone, for the treatment of HIV-1 infection

Commonly used brand name(s)

In the U.S.

  • Trizivir

Available Dosage Forms:

  • Tablet

Therapeutic Class: Antiretroviral Agent

Pharmacologic Class: Abacavir

Proper Use of abacavir, lamivudine, and zidovudine

Take abacavir, lamivudine, and zidovudine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not start or stop taking abacavir, lamivudine, and zidovudine combination without checking first with your doctor.

abacavir, lamivudine, and zidovudine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

You may take abacavir, lamivudine, and zidovudine with or without food.

abacavir, lamivudine, and zidovudine will be given together with other medicines for HIV infection. Take all of the medicines your doctor gives you at the right time of day. These medicines work best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. If you need help in planning the best times to take your medicines, check with your doctor.

When your supply of abacavir, lamivudine, and zidovudine runs low, get more from your pharmacy or from your doctor. The amount of virus in your blood may increase if the medicine is stopped, even for a short time. The virus may develop resistance to abacavir, lamivudine, and zidovudine and be harder to treat.

Only take medicine that your doctor has prescribed specifically for you. Do not share your medicine with others.

Abacavir, lamivudine, and zidovudine combination contains a fixed amount of each medicine in the tablet.

Dosing

The dose of abacavir, lamivudine, and zidovudine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of abacavir, lamivudine, and zidovudine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For human immunodeficiency virus (HIV) infection:
      • Adults and children who weigh at least 40 kilograms (kg)—One tablet two times per day.
      • Children who weighs less than 40 kg—Use is not recommended.

Missed Dose

If you miss a dose of abacavir, lamivudine, and zidovudine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

How do I store and/or throw out Abacavir, Lamivudine, and Zidovudine?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Dosing Hepatic Impairment

Mild impairment (Child-Pugh class A): Use is not recommended (use dose-adjusted individual components).

Moderate to severe hepatic impairment (Child-Pugh Class B or C): Use is contraindicated.

Adverse Reactions

See individual agents as well as other combination products for additional information. Frequency not always defined.

Central nervous system: Headache (13%), fatigue (12%), malaise (12%), depression (6%), anxiety (5%),

Dermatologic: Skin rash (5%)

Endocrine & metabolic: Increased amylase (2%), increased serum triglycerides (grade 3-4: 2%), increased gamma-glutamyl transferase, redistribution of body fat

Gastrointestinal: Nausea (19%), nausea and vomiting (10%), diarrhea (7%), pancreatitis

Hematologic & oncologic: Neutropenia (5%)

Hepatic: Increased serum ALT (6%)

Hypersensitivity: Hypersensitivity (1% to 9%; based on abacavir component; higher risk in carriers of the HLA-B*5701 allele)

Immunologic: Immune reconstitution syndrome

Infection: Viral infection (5%)

Miscellaneous: Fever and chills (6%)

Neuromuscular & skeletal: Increased creatine phosphokinase (7%)

Respiratory: ENT infection (5%)

<1% (Limited to important or life-threatening): Abdominal pain, allergic sensitization (including anaphylaxis), alopecia, anemia, anorexia, aplastic anemia, cardiomyopathy, decreased appetite, dyspepsia, erythema multiforme, exacerbation of hepatitis B (posttreatment), gynecomastia, increased serum bilirubin, increased serum transaminases, insomnia, lactic acidosis, liver steatosis, lymphadenopathy, myalgia, myasthenia, oral mucosa hyperpigmentation, paresthesia, peripheral neuropathy, rhabdomyolysis, seizure, sleep disorder, splenomegaly, Stevens-Johnson syndrome, stomatitis, thrombocytopenia, urticaria, vasculitis, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• Hematologic toxicity: [US Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise (eg, granulocyte count <1,000 cells/mm3 or hemoglobin <9.5 g/dL). Frequent complete blood counts are recommended in patients with advanced HIV-1 disease. Dosage interruption may be needed if anemia or neutropenia develops.

• Hypersensitivity reactions: [US Boxed Warning]: Serious hypersensitivity reactions (sometimes fatal) have occurred in patients taking abacavir (in Trizivir). 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 therapy with Trizivir or reinitiation of therapy with Trizivir unless patients have had a previously documented HLA-B*5701 allele assessment. Discontinue Trizivir if a hypersensitivity reaction is suspected. Trizivir is contraindicated in patients who have the HLA-B*5701 allele or in patients with a prior hypersensitivity reaction to abacavir. Reintroduction of Trizivir or any other 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. Additionally, allele-positive patients (including abacavir treatment naive) should have an allergy to abacavir documented in their medical record. 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] 2015). These reactions usually include signs or symptoms in 2 or more of the following groups: fever; rash; gastrointestinal (eg, nausea, vomiting, diarrhea, abdominal pain); constitutional (eg, generalized malaise, fatigue, achiness); respiratory (eg, dyspnea, cough, pharyngitis). 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. Trizivir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Following a hypersensitivity reaction, Trizivir SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. If Trizivir is to be 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 Trizivir 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: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and 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).

• Myopathy: [US Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.

• Pancreatitis: Pancreatitis has been observed with abacavir, lamivudine and zidovudine; rule out pancreatitis in patients who develop signs/symptoms (eg, nausea/vomiting, abdominal pain, elevated lipase and amylase) during therapy.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Exacerbation of hepatitis B (including fatalities) has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function (eg, serum ALT) and HBV viral DNA closely for several months after discontinuing Trizivir in coinfected patients.

• Coronary heart disease: Use has been associated with an increased risk of myocardial infarction (MI) in observational studies; however, based on a meta-analysis of 26 randomized trials, the FDA has concluded there is not an increased risk. 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.

• Lamivudine-resistant HBV: Emergence of HBV virus variants associated with resistance to lamivudine have been reported in HIV-1 infected subjects who have received lamivudine-containing antiretroviral regimens in the presence of HBV coinfection.

• Renal impairment: Trizivir, as a fixed-dose combination tablet, should not be used in patients with CrCl <50 mL/minute.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric patients <40 kg: Trizivir, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment.

• Therapy-experienced patients: Patients with prolonged prior nucleoside reverse transcriptase inhibitor (NRTI) exposure or presence of HIV-1 isolates containing multiple mutations conferring resistance to NRTIs have limited response to abacavir. The potential for cross resistance between abacavir and other NRTIs should be considered when evaluating new regimens in therapy experienced patients.

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