Abacavir

Name: Abacavir

What is abacavir?

Abacavir is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body.

Abacavir is used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). This medicine is for adults and children who are at least 3 months old. Abacavir is not a cure for HIV or AIDS.

Abacavir may also be used for purposes not listed in this medication guide.

Commonly used brand name(s)

In the U.S.

  • Ziagen

Available Dosage Forms:

  • Tablet
  • Solution

Therapeutic Class: Antiretroviral Agent

Pharmacologic Class: Nucleoside Reverse Transcriptase Inhibitor

Uses For abacavir

Abacavir is used together with other medicines to treat human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immunodeficiency syndrome (AIDS).

Abacavir will not cure or prevent HIV infection or the symptoms of AIDS. It helps keep the HIV virus from reproducing, and appears to slow the destruction of the immune system. This may help delay the development of serious health problems that are usually related to AIDS or HIV infection. Abacavir will not keep you from spreading HIV to other people. People who receive abacavir may continue to have other problems related to AIDS or HIV infection.

abacavir is available only with your doctor's prescription.

Before Using abacavir

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For abacavir, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to abacavir or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of abacavir in children younger than 3 months of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of abacavir in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving abacavir.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking abacavir, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using abacavir with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Orlistat
  • Ribavirin

Using abacavir with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Methadone
  • Tipranavir

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of abacavir. Make sure you tell your doctor if you have any other medical problems, especially:

  • Diabetes or
  • Heart disease or
  • Hyperlipidemia (high cholesterol or fats in the blood) or
  • Hypertension (high blood pressure)—Use with caution. May make these conditions worse.
  • Genetic condition (eg, gene variation called HLA-B*5701)—This condition may increase the risk for serious and life-threatening side effects.
  • Liver disease, mild—Use with caution. The effects may be increased because of slower removal of the medicine to the body.
  • Liver disease, moderate or severe—Should not be used in patients with this condition.

abacavir Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common
  • Abdominal or stomach pain
  • cough
  • diarrhea
  • difficult or labored breathing
  • fever
  • headache
  • joint or muscle pain
  • nausea
  • numbness or tingling of the hands, feet, or face
  • redness and soreness of the eyes
  • skin rash
  • sore throat
  • sores in the mouth
  • swelling of the feet or lower legs
  • unusual feeling of discomfort or illness
  • unusual tiredness
  • vomiting
Rare
  • Abdominal or stomach swelling
  • decreased appetite
  • fast, shallow breathing
  • sleepiness
Incidence not known
  • Blistering, peeling, or loosening of the skin
  • chest pain or discomfort
  • chills
  • dark urine
  • itching
  • light-colored stools
  • pain or discomfort in the arms, jaw, back, or neck
  • red, irritated eyes
  • red skin lesions, often with a purple center
  • sores, ulcers, or white spots in the mouth or on the lips
  • sweating
  • unusual weakness
  • upper right abdominal or stomach pain
  • yellow eyes and skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Headache
Less common
  • Trouble sleeping
Incidence not known
  • Breast enlargement
  • buffalo hump
  • central obesity
  • facial wasting
  • gaining weight around your neck, upper back, breast, face, or waist
  • peripheral wasting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Brand Names U.S.

  • Ziagen

Dosing Hepatic Impairment

Mild impairment (Child-Pugh class A): 200 mg twice daily (oral solution is recommended).

Moderate to severe impairment (Child-Pugh class B or C): Use is contraindicated (has not been studied).

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).

• Hypersensitivity reactions: [US Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. 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 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] 2015). 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 should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Abacavir SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. If abacavir 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 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: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; 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).

Disease-related concerns:

• 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.

• Hepatic impairment: Use with caution and adjust dosage in patients with mild hepatic impairment (contraindicated in moderate to severe impairment).

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.

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).

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

• Sorbitol: Oral solution contains sorbitol. Use oral solution with caution in patients who are fructose intolerant; may experience abdominal discomfort and/or diarrhea with administration of the oral solution.

Other warnings/precautions:

• Appropriate use: Abacavir should always be used as a component of a multidrug regimen. Do not use abacavir/lamivudine (plus efavirenz or plus atazanavir/ritonavir) in adolescent and adult HIV-1 patients with a pre-ART HIV RNA >100,000 copies/mL (HHS [adult] 2015).

Pharmacology

Mechanism of Action

Guanosine analog that inhibits HIV-1 reverse transcriptase by competing with dGTP as substrate, which in turn inhibits viral replication

Pharmacokinetics

Absorption: Rapid & extensive absorption

Vd: 0.86 L/kg

Protein Bound: 50%

Metabolism: hepatic via alcohol dehydrogenase & glucuronyl transferase to inactive carboxylate & glucuronide metabolites

Bioavailability: 83%

Half-life elimination: 1.5 hr

Peak Plasma Time: 0.7-1.7 hr

Excretion: Urine (80%); feces (16%)

Pharmacogenomics

Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction

Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended

For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended

Genetic testing laboratories

  • The following companies provide genetic testing for HLA variants
  • Kashi Clinical Laboratories (www.kashilab.com)
  • LabCorp (http://www.labcorp.com/)
  • Specialty Laboratories (http://www.specialtylabs.com)
  • Quest (http://www.questdialgnotics.com)

Abacavir Genetic Information

Some patients carry a version of a gene (called an allele) that makes them more susceptible to having a severe allergic reaction to abacavir. This allele is called human leukocyte antigen-B*5701 (HLA-B*5701). This allele codes for a protein that is involved in your body's immune response to infections and foreign bodies.

HLA-B*5701 testing is done to determine if you are at a high risk of having a severe, life-threatening allergic reaction to abacavir. If you have this HLA-B*5701 allele, your doctor may decide not to treat you with abacavir. If you test negative for this mutation, you may still experience an allergic reaction, but it will be less likely than if you tested positive for the mutation.

The HLA-B*5701 protein is involved in your body'a immune response. Having this protein puts your immune system into overdrive, which puts you at an increased risk of having an allergic reaction to abacavir.

 

Abacavir Brand Names

Abacavir may be found in some form under the following brand names:

  • Epzicom

  • Trizivir

  • Ziagen

Abacavir Drug Class

Abacavir is part of the drug class:

  • Nucleoside and nucleotide reverse transcriptase inhibitors

Abacavir Levels and Effects while Breastfeeding

Summary of Use during Lactation

In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. Published experience with abacavir during breastfeeding is limited. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, World Health Organization guidelines recommend that all women with an HIV infection who are pregnant or breastfeeding should be maintained on antiretroviral therapy for at least the duration of risk for mother-to-child transmission. Mothers should exclusively breastfeed their infants for the first 6 months of life; breastfeeding with complementary feeding should continue through at least 12 months of life up to 24 months of life.[1] The first choice regimen for nursing mothers is tenofovir, efavirenz and either lamivudine or emtricitabine. If these drugs are unavailable, alternative regimens include: 1) zidovudine, lamivudine and efavirenz; 2) zidovudine, lamivudine and nevirapine; or 3) tenofovir, nevirapine and either lamivudine or emtricitabine. Exclusively breastfed infants should also receive 6 weeks of prophylaxis with nevirapine.[2][3]

Drug Levels

Maternal Levels. Fifteen women had been taking abacavir 300 mg twice daily for 53 to 182 days as part of a 3-drug combination that included zidovudine and lamivudine. Breastmilk samples were collected at just before a dose at a median of 1 month postpartum. Whole breastmilk levels contained a median of 0.057 mg/L of abacavir, which was a median of 85% of maternal blood levels.[4]

Infant Levels. Nine infants were breastfed either partially or exclusively by their mothers who had been taking abacavir 300 mg twice daily for 53 to 182 days as part of a 3-drug combination that included zidovudine and lamivudine. Infant blood was collected at a median of 1 month postpartum 11 to 17 hours after the mothers previous dose, and at a median of 1 hour (range 6 minutes to 35 hours) after the last breastfeeding. Eight of 9 infants studied had undetectable (<16 mcg/L) plasma abacavir levels.[4]

Effects in Breastfed Infants

An HIV-positive mother took a combination tablet containing dolutegravir 50 mg, abacavir sulfate 600 mg and lamivudine 300 mg (Triumeq) once daily. Her infant was exclusively breastfed for about 30 weeks and partially breastfed for about 20 weeks more. No obvious side effects were noted.[5]

Effects on Lactation and Breastmilk

Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen.[6][7][8] Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients,[9][10] although this has been disputed.[11] The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

References

1. Anon. Guideline: Updates on HIV and infant feeding: The duration of breastfeeding, and support from health services to improve feeding practices among mothers living with HIV. Geneva: World Health Organization. 2016. PMID: 27583316

2. World Health Organization. HIV and infant feeding: update. 2007. http://whqlibdoc.who.int/publications/2007/9789241595964_eng.pdf

3. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva: World Health Organization. 2013. http://www.who.int/hiv/pub/guidelines/arv2013/en/

4. Shapiro RL, Rossi S, Ogwu A et al. Therapeutic levels of lopinavir in late pregnancy and abacavir passage into breast milk, in the Mma Bana Study, Botswana. Antivir Ther. 2013;18:585-90. PMID: 23183881

5. Kobbe R, Schalkwijk S, Dunay G et al. Dolutegravir in breast milk and maternal and infant plasma during breastfeeding. AIDS. 2016;30:2731-3. PMID: 27782968

6. Garcia-Benayas T, Blanco F, Martin-Carbonero L et al. Gynecomastia in HIV-infected patients receiving antiretroviral therapy. AIDS Res Hum Retroviruses. 2003;19:739-41. PMID: 14585204

7. Pantanowitz L, Evans D, Gross PD, Dezube BJ. HIV-related gynecomastia. Breast J. 2003;9:131-2. PMID: 12603389

8. Evans DL, Pantanowitz L, Dezube BJ, Aboulafia DM. Breast enlargement in 13 men who were seropositive for human immunodeficiency virus. Clin Infect Dis. 2002;35:1113-9. PMID: 12384846

9. Hutchinson J, Murphy M, Harries R, Skinner CJ. Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet. 2000;356:1003-4. PMID: 11041407

10. Orlando G, Brunetti L, Vacca M. Ritonavir and saquinavir directly stimulate anterior pituitary prolactin secretion, in vitro. Int J Immunopathol Pharmacol. 2002;15:65-8. PMID: 12593790

11. Montero A, Bottasso OA, Luraghi MR et al. Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Lancet. 2001;357:473-4; author reply 475. PMID: 11273087

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