Ziagen


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Related to Ziagen: Abacavir, lamivudine

abacavir sulfate

Ziagen

Pharmacologic class: Carbocyclic nucleoside reverse transcriptase

Therapeutic class: Antiretroviral

Pregnancy risk category C

FDA Box Warning

• Drug may cause serious and potentially fatal hypersensitivity reactions, including multi-organ syndrome marked by fever, rash, GI distress, malaise, fatigue, achiness, dyspnea, cough, and pharyngitis. Discontinue immediately if you suspect such a reaction. If hypersensitivity can't be ruled out, discontinue permanently, even if other diagnoses are possible.

• After hypersensitivity reaction, never restart drug or other agents containing it, because more severe symptoms (including severe hypotension and death) may arise within hours.

Action

Converts via intracellular enzymes to active metabolite carbovir triphosphate, which inhibits activity of human immunodeficiency virus-1 (HIV-1) reverse transcriptase. Inhibits viral reproduction by interfering with DNA and RNA synthesis.

Availability

Oral solution: 20 mg/ml

Tablets: 300 mg

Indications and dosages

HIV-1 infection

Adults: 300 mg P.O. b.i.d. or 600 mg P.O. daily

Children ages 3 months to 16 years: 8 mg/kg P.O. b.i.d., to a maximum dosage of 300 mg b.i.d.

Contraindications

• Hypersensitivity to drug

• Hepatic disease, lactic acidosis

• Breastfeeding

• Children younger than age 3 months

Precautions

Use cautiously in:

• impaired renal function, bone marrow suppression

• risk factors for hepatic disease

• elderly patients

• pregnant patients.

Administration

• Always give in combination with other antiretrovirals.

Be aware that drug may cause fatal hypersensitivity reactions.

• Give with food if GI upset occurs.

Adverse reactions

CNS: headache, weakness, insomnia

GI: nausea, vomiting, diarrhea, poor appetite, pancreatitis

Hematologic: neutropenia, severe anemia

Hepatic: hepatic failure

Metabolic: mild hyperglycemia, lactic acidosis

Skin: rash, erythema multiforme, toxic epidermal necrolysis

Other: body fat redistribution, Stevens-Johnson syndrome, fatal hypersensitivity reaction, immune reconstitution syndrome

Interactions

Drug-drug. Methadone: Increased oral methadone clearance

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, gamma-glutamyltransferase, glucose, triglycerides: increased levels

Drug-herbs. St. John's wort: decreased drug blood level and reduced drug effect

Drug-behaviors. Alcohol use: increased drug half-life and concentration

Patient monitoring

Assess for severe lactic acidosis, especially in women and obese patients.

Evaluate closely for signs and symptoms of hypersensitivity reaction, which can be fatal. These include fever, rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, dyspnea, cough, and pharyngitis.

Be aware that immune reconstitution syndrome may occur in patients receiving combination antiretroviral therapy. During initial phase of therapy, patient whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, and tuberculosis), which may necessitate further evaluation and treatment.

Never restart therapy if patient has experienced a previous hypersensitivity reaction to this drug.

• Check for liver enlargement.

• Monitor CBC, serum electrolytes, and liver and kidney function test results.

Patient teaching

• Advise patient to take drug with food to minimize GI upset.

• Instruct patient to refrigerate drug but not to freeze it.

Teach patient how to recognize hypersensitivity reaction. Instruct him to stop taking drug and contact pre-scriber immediately if signs or symptoms of such a reaction occur.

Tell patient to contact prescriber if he develops a rash (possible sign of Stevens-Johnson syndrome).

Instruct patient to immediately report signs and symptoms of immune reconstitution syndrome (such as new signs and symptoms of a previously subclinical infection, worsening or progression of a known infection despite treatment, a new infection or illness, or failure of antiretroviral therapy).

• Inform patient that drug doesn't cure HIV but lowers viral count.

• Instruct patient to obtain medication guide and warning card with each refill.

• Tell patient he'll undergo frequent blood and urine testing during therapy.

• Advise patient to consult prescriber before drinking alcohol or using herbs.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

abacavir

(ah-back-ah-veer) ,

Ziagen

(trade name)

Classification

Therapeutic: antiretrovirals
Pharmacologic: nucleoside reverse transcriptase inhibitors
Pregnancy Category: C

Indications

Management of HIV infection (AIDS) in combination with other antiretrovirals (not with lamivudine and/or tenofovir).

Action

Converted inside cells to carbovir triphosphate, its active metabolite. Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase, which in turn terminates viral DNA growth.

Therapeutic effects

Slows the progression of HIV infection and decreases the occurrence of its sequelae.
Increases CD4 cell counts and decreases viral load.

Pharmacokinetics

Absorption: Rapidly and extensively (83%) absorbed.
Distribution: Distributes into extravascular space and readily distributes into erythrocytes.
Metabolism and Excretion: Mostly metabolized by the liver; 1.2% excreted unchanged in urine.
Half-life: 1.5 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
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Contraindications/Precautions

Contraindicated in: Hypersensitivity (rechallenge may be fatal); Lactation: Breast feeding not recommended for HIV-infected patients.
Use Cautiously in: Coronary heart disease; Obstetric: Safety not established; Pediatric: Children <3 mo (safety not established).
Exercise Extreme Caution in: genetic implication Patients positive for HLA-B*5701 allele (unless exceptional circumstances exist where benefits clearly outweigh the risks).

Adverse Reactions/Side Effects

Central nervous system

  • headache
  • insomnia

Cardiovascular

  • myocardial infarction (life-threatening)

Gastrointestinal

  • hepatomegaly (with steatosis) (life-threatening)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • anorexia

Dermatologic

  • rashes

Fluid and Electrolyte

  • lactic acidosis (life-threatening)

Miscellaneous

  • hypersensitivity reactions (life-threatening)
  • fat redistribution
  • immune reconstitution syndrome

Interactions

Drug-Drug interaction

Alcohol ↑ blood levels.May ↑ methadone metabolism in some patients; slight ↑ in methadone dosing may be needed.

Route/Dosage

Oral (Adults) 300 mg twice daily.
Oral (Children 3 mo–16 yr) 8 mg/kg twice daily (not to exceed 300 mg twice daily).

Availability (generic available)

Tablets: 300 mg
Oral solution (strawberry/banana flavor): 20 mg/mL
In combination with: lamivudine (Epzicom); lamivudine and zidovudine (Trizivir). See combination drugs.

Nursing implications

Nursing assessment

  • Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections throughout therapy.
  • Assess for signs of hypersensitivity reactions (fever; rash; gastrointestinal—nausea, vomiting, diarrhea, abdominal pain; constitutional—malaise, fatigue, achiness; respiratory—dyspnea, cough, pharyngitis). May also cause elevated liver function tests, increased creatine phosphokinase or creatinine, and lymphopenia. genetic implication Patients who carry the HLA-B*5701 allele are at high risk for hypersensitivity reaction. Discontinue promptly if hypersensitivity reaction is suspected. Regardless of HLA-B*5701 status, permanently discontinue abacavir if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Following a hypersensitivity reaction, never restart abacavir or abacavir-containing products. More severe symptoms may occur within hours and may include life-threatening hypotension and death. Symptoms usually resolve upon discontinuation.
  • May cause lactic acidosis and severe hepatomegaly with steatosis. Monitor patient for signs (↑ serum lactate levels, ↑ liver enzymes, liver enlargement on palpation). Therapy should be suspended if clinical or laboratory signs occur.
  • Lab Test Considerations: Monitor viral load and CD4 cell count regularly during therapy.
    • genetic implication Screen for HLA-B*5701 allele prior to initiation of therapy to decrease risk of hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir.
    • Monitor liver function. May cause ↑ levels of AST, ALT, and alkaline phosphatase, which usually resolve after interruption of therapy. Lactic acidosis may occur with hepatic toxicity, causing hepatic steatosis; may be fatal, especially in women.
    • May cause ↑ serum glucose and triglyceride levels.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Oral: May be administered with or without food. Oral solution may be stored at room temperature or refrigerated; do not freeze. Tablet may be used with children if able to swallow and dose is correctly calculated.

Patient/Family Teaching

  • Emphasize the importance of taking abacavir as directed. Must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount, and do not stop taking without consulting health care professional. Take missed doses as soon as remembered; do not double doses. Advise patient to read the Medication Guide prior to starting therapy and with each Rx refill in case of changes
  • Instruct patient not to share abacavir with others.
  • Inform patient that abacavir does not cure AIDS or prevent associated or opportunistic infections. Abacavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom, and avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of abacavir are unknown at this time.
  • Advise patient of potential for hypersensitivity reactions that may result in death. Instruct patient to discontinue abacavir and notify health care professional immediately if symptoms of hypersensitivity or signs of Immune Reconstitution Syndrome (signs and symptoms of an infection) occur. Advise patient to read Medication Guide thoroughly with each refill in case of changes. A warning card summarizing symptoms of abacavir hypersensitivity is provided with each prescription; instruct patient to carry card at all times.
  • Instruct patient to notify health care professional immediately if symptoms of lactic acidosis (tiredness or weakness, unusual muscle pain, trouble breathing, stomach pain with nausea and vomiting, cold especially in arms or legs, dizziness, fast or irregular heartbeat) or if signs of hepatotoxicity (yellow skin or whites of eyes, dark urine, light-colored stools, lack of appetite for several days or longer, nausea, abdominal pain) occur. These symptoms may occur more frequently in patients that are female, obese, or have been taking medications like abacavir for a long time.
  • Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially methadone and other antiretrovirals.
  • Advise female patients to avoid breast feeding and to notify health care professional if pregnancy is planned or suspected.
  • Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS, and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and increase in CD4 cell counts.

abacavir

An HIV-nucleoside reverse-transcriptase inhibitor (NRTI/integrase inhibitor) similar to AZT.
 
Adverse effects
Life-threatening allergic reactions—fever, dyspnea, rashes, intraoral blistering, nausea, headache.

Ziagen®

 Abacavir, see there.
References in periodicals archive ?
However, the company published a letter stating that their own analysis did not suggest an increased risk of heart attacks from Ziagen.
The study, which looked at the effect of five individual nucleoside reverse transcriptase inhibitors (NRTIs), showed that treatment with abacavir (Ziagen) was associated with a 90% increased risk of Ml, and didanosine was associated with a 49% increased risk.
Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infected adults: results of the Ziagen Once Daily in Antiretroviral Combination Study.
Table 1 Common Antiretroviral Drugs (14-16) Classification Generic Name Trade Name Nucleoside reverse Abacavir sulfate Ziagen transcriptase inhibitors Abacavir sulfate + Trizivir (NRTI) lamivudine + zidovudine Didanosine (ddl) Videx, Videx EC Lamivudine (3TC) Epivir Lamiudine + zidovudine Combivir Stavudine (d4T) Zerit Tenofovir disoproxil Viread fumarate Zalcitabine (ddC) Hivid Zidovudine (AZT, ZDV) Retrovir Non-nucleoside reverse Delavirdine mesylate Rescriptor transcriptase inhibitors Efavirenz Sustiva (NNRTI) Nevirapine Viramune Protease inhibitors (PI) Amprenavir Agenerase Indinavir sulfate Crixivan Lopinavir + ritonavir Kaletra Nelfinavir Viracept Ritonavir Norvir Saquinavir Fortovase Saquinavir mesylate Invirase Fusion inhibitors (FI) Enfuvirtide Fuzeon
Glaxo will supply more than 90,000 treatment packs of its drugs - Combivir, Epivir and Ziagen - to the Russian Government by the end of 2006.
Some side effects are life threatening, such as the hypersensitivity reaction associated with Ziagen and the inflammation of the pancreas that can occur with stavudine and didanosine.
A study in Australia showed that a genetic test was very effective in predicting which patient would react badly to abacavir (Ziagen) [1,2].
Trizivir combines the NRTIs zidovudine (Retrovir), lamivudine (Epivir), and abacavir (Ziagen) into one tablet.
Those products include Retrovir (zidovudine), Combivir (lamivudine/zidovudine), Epivir (lamivudine), Trizivir (abacavir, lamivudine, and zidovudine), Ziagen (abacavir), and Zofran (ondansetron), according to the company.
Epzicom is a "nuke" and is a combination of Epivir (3TC) and Ziagen (avacavir).
GlaxoSmithKline (GSK) and Australian researchers have independently developed a pharmacogenetic test for Abacavir (ziagen), a licensed HIV/AIDS drug that causes serious and potentially fatal hypersensitivity reactions in approximately 5% of patients, usually within the first six weeks of therapy.