Ziagen
Classes: HIV, NRTIs, Antiretroviral Agents
Dosage Forms & Strengths
oral solution
20mg/mL
tablet
300mg
HIV Infection
Indicated for treatment of HIV infection in combination with other antiretroviral agents
300 mg PO q12hr, OR
600 mg PO qDay
Dosage Modifications
Renal impairment: No dosage adjustment required
Hepatic impairment
Moderate-to severe (Child-Pugh B or C): Contraindicated
Mild (Child-Pugh A); adults and adolescents aged ≥16 years: Reduce dose to 200 mg q12hr (use oral solution)
Contraindicated
elvitegravir/cobicistat/emtricitabine/tenofovir DF
Serious - Use Alternative
ganciclovir
ribavirin
valganciclovir
Monitor Closely
cabozantinib
didanosine
efavirenz
emtricitabine
atazanavir
enfuvirtide
fosamprenavir
indinavir
lamivudine
methadone
nelfinavir
nevirapine
orlistat
ritonavir
saquinavir
stavudine
tenofovir DF
tipranavir
tipranavir
zidovudine
Minor
ethanol
Adverse Effects
>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
Warnings
Hypersensitivity reactions
Severe and sometimes fatal hypersensitivity reaction, with multiple organ involvement, have occurred
Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction; although, hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele
Contraindicated with history of prior hypersensitivity reaction to abacavir and in patients who are HLA-B*5701-positive
All patients should be screened for the HLA-B*5701 allele before initiating or reinitiating abacavir, unless patients have a previously documented HLA-B*5701 allele assessment
If hypersensitivity is suspected, discontinue abacavir immediately, regardless of HLA-B*5701 status and even when other diagnoses are possible
Contraindications
Prior hypersensitivity reaction to abacavir
Presence of HLA-B*5701 allele
Moderate or severe hepatic impairment
Cautions
Increased risk of serious or fatal hypersensitivity reactions; patients with human leukocyte antigen allele, HLA-B*5701 are at a higher risk; do not restart abacavir following hypersensitive reaction; may cause hypotension, multiorgan failure, and/or death (see Contraindications and Black Box Warnings)
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogues, including abacavir; a majority of these cases have been in women; female gender and obesity may be risk factors; suspend dosing in those who develop clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity
Immune reconstitution syndrome reported with combination ART; during the initial treatment phase, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis); autoimmune disorders (eg, Grave disease, polymyositis, and Guillain-Barré syndrome) have also been reported
Use has been associated with increased risk of myocardial infarction in observational studies, but not in a meta-analysis of 26 randomized trials; caution with risks for coronary heart disease and minimizing modifiable risk factors, including smoking, hypertension, and hyperlipidemia, prior to use
Drug interaction overview
Methadone
In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with abacavir 600 mg BID (twice the currently recommended dose), PO methadone clearance increased
This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients
Pregnancy
Healthcare Providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
Available data from the APR show no difference in the overall risk of birth defects for abacavir compared with the background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population
In animal reproduction studies, oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the recommended clinical daily dose; however, no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis, at exposures approximately 9 times the human exposure (AUC) at the recommended clinical dose
Lactation
Abacavir is present in human milk; there is no information on effects of abacavir on breastfed infant or effects of drug on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV- positive infants), and (3) serious adverse reactions in breastfed infant, instruct mothers not to breastfeed if they are receiving abacavir
Pregnancy Category Definitions
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
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%)
Absorption
Rapid and extensive PO absorption
Bioavailability: 83%
Peak plasma concentration: 3 mcg/mL (300 mg); 4.26 mcg/mL (600 mg)
AUC: 6.02 mcg·h/mL (300 mg); 11.95 mcg·h/mL (600 mg)
Distribution
Vd: 0.86 L/kg
Protein Bound: 50%
Metabolism
Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites
Elimination
Half-life: 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
Oral Administration
May take with or without food
ليست هناك تعليقات:
إرسال تعليق