Ziagen

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Abacavir comes with a Medication Guide and a Warning Card that lists the symptoms of an allergic reaction. Read this information carefully and carry the Warning Card with you at all times so you will know what symptoms to watch for.

Abacavir can be taken with or without food.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

While using abacavir, you may need frequent blood tests.

Use abacavir regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store at room temperature away from moisture and heat.

You may store the oral solution (liquid) in the refrigerator but do not let it freeze.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Do not allow your medicine to run out completely before you get your prescription refilled. It is important that you not stop taking abacavir once you have started. If you miss several doses, you may have a dangerous or even fatal allergic reaction once you start taking abacavir again.

>10%

Nausea (17-19%)

Headache (9-13%)

Malaise/Fatigue (12%)

Nausea & vomiting (10%)

1-10%

Hypersensitivity reaction (2-8%)

Diarrhea (5-7%)

Musculoskelatal pain (5-7%)

Hypertriglyceridemia (6%)

Hepatic: AST Increased (6%)

Depression (4-6%)

Fever/chills (3-6%)

Viral respiratory infections (5%)

Ear/nose /throat infections (4-5%)

Rash (4-5%)

Anxiety (3-5%)

Thrombocytopenia (1%)

<1%

Anaphylactoid reaction

Pulmonary hypertension

Erythema multiforme

Redistribution/accumulation of body fat

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Pancreatitis

GGT increased

Hepatic steatosis

Heptaomegaly

Hepatotoxicity

Lactic acidosis

MI

Ziagen can cause the following serious side effects:

• Serious allergic reaction that can cause death. (See "Drug Precautions".)
• Lactic acidosis with liver enlargement (hepatomegaly) that can cause death. (See "Drug Precautions".)
• Changes in immune system. When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis. If you have new symptoms after starting your HIV medicines, be sure to tell your doctor.
• Changes in body fat. These changes have happened in patients taking antiretroviral medicines like Ziagen. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known.

Some HIV medicines including Ziagen may increase your risk of heart attack. If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes, tell your doctor.

The most common side effects of Ziagen include nausea, vomiting, tiredness, headache, diarrhea, trouble sleeping, fever and chills, and loss of appetite. Most of these side effects did not cause people to stop taking Ziagen.

This list of side effects is not complete. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

If you take too much Ziagen, call your doctor or poison control center right away.

If Ziagen is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Do not allow your medicine to run out completely before you get your prescription refilled. It is important that you not stop taking abacavir once you have started. If you miss several doses, you may have a dangerous or even fatal allergic reaction once you start taking abacavir again.

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).1 2 3 46 200

In the U.S.

• Ziagen

Available Dosage Forms:

• Tablet
• Solution

Therapeutic Class: Antiretroviral Agent

Pharmacologic Class: Nucleoside Reverse Transcriptase Inhibitor

Ziagen tablets contain 300 mg of abacavir as abacavir sulfate. The tablets are yellow, biconvex, scored, capsule-shaped, film-coated, and imprinted with “GX 623” on both sides.

Ziagen oral solution contains 20 mg per mL of abacavir as abacavir sulfate. The solution is a clear to opalescent, yellowish, strawberry-banana-flavored liquid.

Ziagen tablets, containing abacavir sulfate equivalent to 300 mg abacavir are yellow, biconvex, scored, capsule-shaped, film-coated, and imprinted with “GX 623” on both sides. They are packaged as follows:

Bottles of 60 tablets (NDC 49702-221-18).

Unit dose blister packs of 60 tablets (NDC 49702-221-44). Each pack contains 6 blister cards of 10 tablets each.

Store at controlled room temperature of 20° to 25°C (68° to 77°F) (see USP).

Ziagen oral solution is a clear to opalescent, yellowish, strawberry-banana-flavored liquid. Each mL of the solution contains abacavir sulfate equivalent to 20 mg of abacavir. It is packaged in plastic bottles as follows:

Bottles of 240 mL (NDC 49702-222-48) with child-resistant closure. This product does not require reconstitution.

Store at controlled room temperature of 20° to 25°C (68° to 77°F) (see USP). DO NOT FREEZE. May be refrigerated.

Common side effects of Ziagen include: arthralgia, cough, fatigue, lethargy, myalgia, pruritus, vomiting, chills, and malaise. Other side effects include: hypersensitivity, pharyngitis, and tachypnea. See below for a comprehensive list of adverse effects.

Applies to abacavir: oral solution, oral tablet

General

In 1 study, patients receiving the once-daily regimen had a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea than patients on the twice-daily regimen.

Many of the side effects listed occurred commonly in patients with abacavir (the active ingredient contained in Ziagen) hypersensitivity (e.g., nausea, vomiting, diarrhea, fever, lethargy, rash).[Ref]

Hypersensitivity

Common (1% to 10%): Drug hypersensitivity, hypersensitivity reaction (including fever, rash [maculopapular, urticarial], nausea, vomiting, malaise, diarrhea, headache, fatigue, myalgia, achiness, abdominal pain, pharyngitis, dyspnea, cough, lethargy, myolysis, edema, elevated liver function tests, mucous membrane lesions [conjunctivitis, mouth ulceration], sore throat, adult respiratory distress syndrome, respiratory failure, lymphadenopathy, hypotension, anaphylaxis, paresthesia, lymphopenia, hepatitis, liver failure, arthralgia, elevated creatine phosphokinase, elevated creatinine, renal failure, erythema multiforme, abnormal chest x-ray findings [mainly localized infiltrates], death)
Frequency not reported: Serious and sometimes fatal hypersensitivity reactions, abacavir (the active ingredient contained in Ziagen) hypersensitivity reaction presenting as acute fibrinous and organizing pneumonia[Ref]

Serious and sometimes fatal hypersensitivity reactions have been reported with this drug. Such reactions have included multi-organ failure and anaphylaxis and usually occurred within the first 6 weeks of therapy (median onset: 9 to 11 days); however, abacavir hypersensitivity reactions have occurred any time during therapy.

Patients with the human leukocyte antigen subtype B*5701 (HLA-B*5701) allele are at higher risk of hypersensitivity reactions to this drug; however, such reactions have occurred in patients without the HLA-B*5701 allele. Abacavir hypersensitivity was reported in about 8% of patients in 9 clinical trials with abacavir-containing products where patients were not screened for the HLA-B*5701 allele; incidence of suspected abacavir hypersensitivity reactions was 1% in clinical trials where HLA-B*5701 carriers were excluded.

Abacavir hypersensitivity reactions have been characterized by at least 2 of the following key signs/symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, achiness); (5) respiratory symptoms (including dyspnea, cough, pharyngitis). Almost all reactions have included fever and/or rash (usually maculopapular or urticarial); however, reactions also reported without fever or rash. Signs/symptoms reported in at least 10% of patients with hypersensitivity reaction have included rash, nausea, vomiting, malaise, diarrhea, headache, fatigue/lethargy, abdominal pain, dyspnea, cough, fever, elevated liver function tests, and myalgia. Other signs/symptoms of hypersensitivity have included mouth ulceration, sore throat, adult respiratory distress syndrome, respiratory failure, edema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis, paresthesia, lymphopenia, hepatitis, liver failure, myolysis, arthralgia, elevated creatine phosphokinase, elevated creatinine, renal failure, abnormal chest x-ray findings (mainly infiltrates, which were localized), and death.

Symptoms of abacavir hypersensitivity reaction worsened with continued therapy and generally resolved when this drug was discontinued. Restarting this drug after a hypersensitivity reaction has resulted in more severe symptoms within hours and included life-threatening hypotension and death. Rarely, life-threatening reactions have occurred within hours after restarting this drug in patients who stopped it for reasons other than symptoms of hypersensitivity (or who stopped it with only 1 key symptom of hypersensitivity).

In 1 case report, a 57-year-old HIV-positive male presented to medical attention with a 2-day history of fever, malaise, and diarrhea related to initiation of this drug. Six days prior to the onset of symptoms, the patient's antiretroviral therapy was switched from efavirenz and lamivudine-zidovudine to zidovudine, abacavir, and lopinavir-ritonavir after a drop in his CD4 cell count. The patient developed acute dyspnea and severe hypoxemia, hemoptysis, and diffuse bilateral pulmonary infiltrates within 72 hours of admission and this drug was discontinued due to suspicion of a hypersensitivity reaction. Three days after drug discontinuation, the patient's status improved and chest films showed resolution of infiltrates.[Ref]

Gastrointestinal

Pancreatitis was observed in the expanded access program.[Ref]

Very common (10% or more): Nausea (up to 47%), nausea and vomiting (up to 38%), diarrhea (up to 16%)
Common (1% to 10%): Abdominal pain/gastritis/gastrointestinal signs and symptoms, vomiting, abdominal discomfort and pain, abnormal amylase
Rare (0.01% to 0.1%): Pancreatitis[Ref]

Other

Very common (10% or more): Malaise and fatigue (up to 34%), temperature regulation disturbance (up to 19%)
Common (1% to 10%): Fever/pyrexia, lethargy, fatigue, fatigue/malaise, fever and/or chills
Uncommon (0.1% to 1%): Non-site-specific pain
Frequency not reported: Asthenia, reduced alcohol tolerance, disulfiram-like reaction[Ref]

In 1 case report, a 31-year-old HIV-infected male patient switched to this drug and experienced a disulfiram-like reaction with nausea, facial flushing, and tachycardia after alcohol consumption. When the patient was rechallenged with a shot of vodka, the same reaction occurred.

In another case, a 27-year-old HIV-infected male patient switched to this drug and noticed reduced alcohol tolerance. The patient reported that he felt as if he had ingested 1.5 bottles of wine after 3 glasses, with loss of memory until the next morning and vomiting. The patient was able to tolerate small quantities of alcohol or alcohol consumed with food.[Ref]

Nervous system

Very common (10% or more): Headache (up to 31%)
Common (1% to 10%): Headaches/migraine, dizziness, neuropathy[Ref]

Respiratory

Very common (10% or more): Cough (up to 24%), ear/nose/throat infections (up to 19%), nasal signs/symptoms (up to 11%)
Common (1% to 10%): Viral respiratory infections (including viral ear, nose, and throat infection), bronchitis
Frequency not reported: Tachypnea, pharyngitis[Ref]

Musculoskeletal

Elevated creatine phosphokinase (greater than 4 times the upper limit of normal [4 x ULN]) has been reported in up to 8% of patients.[Ref]

Very common (10% or more): Elevated creatine phosphokinase (up to 12%)
Common (1% to 10%): Musculoskeletal pain

Combination antiretroviral therapy:
-Frequency not reported: Osteonecrosis[Ref]

Dermatologic

Very common (10% or more): Skin rashes (maculopapular, urticarial, or variable appearance; up to 11%)
Common (1% to 10%): Rash (without systemic symptoms)
Frequency not reported: Sweet's syndrome
Very rare (less than 0.01%): Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme[Ref]

Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported during postmarketing experience in patients using this drug primarily in combination with agents known to be associated with SJS and TEN, respectively.

Cases of erythema multiforme, SJS, or TEN have been reported very rarely when abacavir hypersensitivity could not be ruled out.[Ref]

Metabolic

Very common (10% or more): Feeding problems (up to 11%)
Common (1% to 10%): Hypertriglyceridemia, hyperamylasemia, anorexia, abnormal triglycerides, hyperlactatemia
Uncommon (0.1% to 1%): Hyperglycemia, abnormal alkaline phosphatase, abnormal glucose, abnormal sodium
Rare (0.01% to 0.1%): Lactic acidosis
Frequency not reported: Mild elevations of blood glucose, hypoglycemia, loss of appetite
Postmarketing reports: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")

Combination antiretroviral therapy:
-Frequency not reported: Metabolic abnormalities (e.g., hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia, hyperlactatemia)[Ref]

Hypertriglyceridemia (greater than 750 mg/dL), hyperamylasemia (greater than 2 x ULN), and hyperglycemia (greater than 13.9 mmol/L) have been reported in up to 6%, up to 4%, and less than 1% of patients, respectively.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.[Ref]

Psychiatric

Very common (10% or more): Dreams/sleep disorders (10%)
Common (1% to 10%): Depression, anxiety, sleep disorders, insomnia, abnormal dreams
Frequency not reported: Mania, worsening of preexisting depression, lethargy[Ref]

Hepatic

Common (1% to 10%): Elevated ALT, elevated AST
Uncommon (0.1% to 1%): Abnormal bilirubin
Frequency not reported: Increased GGT, severe hepatomegaly with steatosis
Postmarketing reports: Hepatic steatosis[Ref]

Elevated ALT (greater than 5 x ULN) and AST (greater than 5 x ULN) have been reported in 6% and up to 6% of patients, respectively.

The reported frequencies were similar to those observed during clinical trials with zidovudine and lamivudine administration.

Increased GGT was observed in the expanded access program.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.[Ref]

Hematologic

Neutropenia (absolute neutrophil count less than 750/mm3), thrombocytopenia (platelets less than 50,000/mm3), anemia (hemoglobin 6.9 g/dL or less), and leukopenia (WBC 1500/mm3 or less) have been reported in up to 5%, 1%, less than 1%, and less than 1% of patients, respectively.

The reported frequencies were similar to those observed during clinical trials with zidovudine and lamivudine administration.

Agranulocytosis has been reported after the addition of this drug to a multi-drug regimen.[Ref]

Common (1% to 10%): Neutropenia, thrombocytopenia, decreased white cells, abnormal absolute neutrophils
Uncommon (0.1% to 1%): Anemia, leukopenia, abnormal hemoglobin, abnormal platelets, abnormal WBC
Rare (less than 0.1%): Eosinophilia
Frequency not reported: Agranulocytosis, increased platelet reactivity[Ref]

Renal

Uncommon (0.1% to 1%): Renal signs/symptoms, abnormal creatinine
Frequency not reported: Acute renal failure, interstitial nephritis[Ref]

Immunologic

Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Cardiovascular

An observational study investigating the rate of MI in patients on combination antiretroviral therapy showed an increased risk of MI with the use of this drug within the previous 6 months. A sponsor-conducted pooled analysis of clinical trials showed no excess risk of MI in abacavir-treated patients as compared with control subjects. Overall, available data from the observational cohort and from clinical trials were inconclusive.[Ref]

Frequency not reported: Endothelial dysfunction, peripheral arterial disease, coronary bypass surgery, ischemic stroke, deep venous thrombosis, angina, transient ischemic attack
Postmarketing reports: Myocardial infarction (MI)[Ref]

Some side effects of Ziagen may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.