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Zidovir is indicated for the
treatment of HIV infection when antiZIDOVIRal therapy is
warranted. ZIDOVIR in combination with other antiZIDOVIRal agents
is indicated for the treatment of HIV infection. ZIDOVIR does not
cure HIV infection/AIDS or prevent passing HIV to others.
Zidovir-100 Capsules
Zidovir-300 Tablets
Zidovir Oral Solution
Warning
ZIDOVIR (ZIDOVUDINE) MAY BE ASSOCIATED WITH HEMATOLOGIC TOXICITY
INCLUDING GRANULOCYTOPENIA AND SEVERE ANAEMIA PARTICULARLY IN
PATIENTS WITH ADVANCED HIV DISEASE (See Warnings and Precautions).
PROLONGED USE OF ZIDOVIR HAS BEEN ASSOCIATED WITH SYMPTOMATIC
MYOPATHY SIMILAR TO THAT PRODUCED BY HUMAN IMMUNODEFICIENCY VIRUS.
RARE OCCURRENCES OF POTENTIALLY FATAL LACTIC ACIDOSIS IN THE
ABSENCE OF HYPOXEMIA, AND SEVERE HEPATOMEGALY WITH STEATOSIS HAVE
BEEN REPORTED WITH THE USE OF CERTAIN ANTIZIDOVIRAL NUCLEOSIDE
ANALOGUES (See Warnings and Precautions).
Composition
Zidovir-100 Capsules
Each capsule contains Zidovudine 100 mg
Zidovir-300 Tablets
Each tablet contains Zidovudine 300 mg
Zidovir Oral Solution
Each 5 ml contains Zidovudine 50 mg
Description
Zidovudine, a thymidine analogue, is an anti-ZIDOVIRal drug acting
against human immunodeficiency virus (HIV).
Indications
Zidovir is indicated for the treatment of HIV infection when
antiZIDOVIRal therapy is warranted.
The duration of clinical benefit from antiZIDOVIRal therapy may be
limited. Alteration in antiZIDOVIRal therapy should be considered
if disease progression occurs during treatment.
Maternal Foetal HIV Transmission: Zidovir is also indicated for
the prevention of maternal foetal HIV transmission. The safety of
zidovudine for the mother or foetus during the first trimester of
pregnancy has not been assessed.
g per day in divided doses in combination with other antiZIDOVIRal
agents and 500 mg (100 mg every 4 hours while awake) or 600 mg per
day in divided doses for monotherapy. The effectiveness of this
dose compared to higher dosing regimens in improving the
neurologic dysfunction associated with HIV disease is unknown.
Dosage and Administration
The recommended total oral daily dose of Zidovir is 600 mg per day
in divided doses in combination with other antiZIDOVIRal agents
and 500 mg (100 mg every 4 hours while awake) or 600 mg per day in
divided doses for monotherapy. The effectiveness of this dose
compared to higher dosing regimens in improving the neurologic
dysfunction associated with HIV disease is unknown.
Paediatrics: The recommended dose in children 3 months to 12 years
of age is 180 mg/m2 every 6 hours (720 mg/m2 per day), not to
exceed 200 mg every 6 hours.
Maternal Foetal HIV Transmission: The recommended dosing regimen
for administration to pregnant women (>14 weeks of pregnancy) and
their neonates is:
Maternal dosing: 100 mg orally 5 times per day until the start of
labour. During labour and delivery, intravenous zidovudine should
be administered at 2 mg/kg (total body weight) over 1 hour
followed by a continuous intravenous infusion of 1 mg/kg/h (total
body weight) until clamping of the umbilical cord.
Infant dosing: 2 mg/kg orally every 6 hours starting within 12
hours after birth and continuing through 6 weeks of age. Infants
unable to receive oral dosing may be administered zidovudine
intravenously at 1.5 mg/kg, infused over 30 minutes, every 6
hours.
Patient Monitoring
Haematologic toxicities appear to be related to pre treatment bone
marrow reserve and to dose and duration of therapy. In patients
with poor bone marrow reserve, particularly in patients with
advanced symptomatic HIV disease, frequent monitoring of
hematologic indices is recommended to detect serious anaemia or
granulocytopenia (See Warnings and Precautions). In patients who
experience hematologic toxicity, reduction in hemoglobin may occur
as early as 2 to 4 weeks, and neutropenia usually occurs after 6
to 8 weeks.
Dose adjustment: Significant anaemia (hemoglobin of <7.5 g/dL or
reduction of >25% of baseline) and/or significant granulocytopenia
(granulocyte count of <750 cells/mm3 or reduction of >50% from
baseline) may require a dose interruption until evidence of marrow
recovery is observed (See Warnings and Precautions). For less
severe anaemia or neutropenia, a reduction in daily dose may be
adequate. In patients who develop significant anaemia, dose
modification does not necessarily eliminate the need for
transfusion. If marrow recovery occurs following dose
modification, gradual increases in dose may be appropriate
depending on hematologic indices and patient tolerance.
In end-stage renal disease patients maintained on hemodialysis or
peritoneal dialysis, recommended dosing is 100 mg every 6 to 8
hours.
There are insufficient data to recommend dosage adjustment of
Zidovir in patients with impaired hepatic function.
Contraindications
Patients who exhibit potentially life-threatening allergic
reactions to any of the components of the formulation.
Warnings and Precautions
Before combination therapy with Zidovir is initiated, consult the
complete prescribing information for each drug. The safety profile
of Zidovir plus other antiZIDOVIRal agents reflects the individual
safety profiles of each component.
The incidence of adverse reactions appears to increase with
disease progression, and patients should be monitored carefully,
especially as disease progression occurs.
BONE MARROW SUPPRESSION
Zidovir should be used with caution in patients who have bone
marrow compromise evidenced by granulocyte count <1000 cells/mm3
or hemoglobin <9.5 g/dL. There have been reports of pancytopenia
associated with the use of zidovudine, which was reversible in
most instances after discontinuance of the drug.
Frequent blood counts are strongly recommended in patients with
advanced HIV disease who are treated with zidovudine. For patients
with asymptomatic or early HIV disease, periodic blood counts are
recommended. If anaemia or neutropenia develops, dosage
adjustments may be necessary (See Dosage and Administration).
MYOPATHY
Myopathy and myositis with pathological changes, similar to that
produced by HIV disease, have been associated with prolonged use
of zidovudine.
LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS
Rare occurrences of potentially fatal lactic acidosis in the
absence of hypoxemia, and severe hepatomegaly with steatosis have
been reported with the use of certain antiZIDOVIRal nucleoside
analogues. Therapy with Zidovir should be suspended until the
diagnosis of lactic acidosis has been excluded. Caution should be
exercised when administering Zidovir to any patient, particularly
obese women, with hepatomegaly, hepatitis, or other known risk
factors for liver disease. Treatment with zidovudine should be
suspended in the setting of rapidly elevating aminotransferase
levels, progressive hepatomegaly, or metabolic/lactic acidosis of
unknown aetiology.
OTHER SERIOUS ADVERSE REACTIONS
Reports of pancreatitis, sensitization reactions, vasculitis and
seizures have been rare. These adverse events, except for
sensitization, have also been associated with HIV disease. Changes
in skin and nail pigmentation have been associated with the use of
zidovudine.
DRUG INTERACTIONS
Ganciclovir, interferon alpha: Use of zidovudine in combination
with either ganciclovir or interferon alpha increases the risk of
hematologic toxicities in some patients with advanced HIV disease.
Hematologic parameters should be monitored frequently in all
patients receiving either of these combinations.
Bone Marrow Suppressive Agents/Cytotoxic Agents: Co administration
of zidovudine with drugs that are cytotoxic or which interfere
with RBC/WBC number or function (e.g. dapsone, flucytosine,
vincristine, vinblastine or adriamycin) may increase the risk of
hematologic toxicity.
Probenecid: Limited data suggests that probenecid may increase
zidovudine levels by inhibiting glucuronidation and/or by reducing
renal excretion of zidovudine.
Phenytoin: Phenytoin plasma levels have been reported to be low in
some patients receiving zidovudine. In one study, a 30% decrease
in oral zidovudine clearance was observed with phenytoin.
Methadone: No adjustments in methadone maintenance requirements
were reported in a study of nine HIV positive patients receiving
methadone maintenance.
Fluconazole: The co administration of fluconazole with zidovudine
has been reported to interfere with the oral clearance and
metabolism of zidovudine.
Atovaquone: A decrease in zidovudine oral clearance was observed.
Valproic Acid: Data suggests that valproic acid increases the oral
bioavailability of zidovudine through inhibition of first pass
hepatic metabolism. Patients should be monitored for a possible
increase in zidovudine related adverse events.
Lamivudine: Co-administration of zidovudine with lamivudine
resulted in an increase in the maximum concentration (Cmax) of
zidovudine.
Other nucleoside analogues: Experimental nucleoside analogues
affecting DNA replication such as ribavirin antagonize the in
vitro antiviral activity of zidovudine against HIV.
PREGNANCY
Category C. Congenital abnormalities were found to occur with
similar frequency between infants born to mothers who received
zidovudine and infants born to mothers who received placebo.
Abnormalities were either problems in embryogenesis (prior to 14
weeks) or were recognised on ultrasound before or immediately
after initiation of study drugs.
NURSING MOTHERS
HIV infected women are advised not to breast feed to avoid
postnatal transmission of HIV to a child who may not yet be
infected. Zidovudine is excreted in human milk.
IMPAIRED RENAL AND HEPATIC FUNCTION
Zidovudine is eliminated from the body primarily by renal
excretion following metabolism in the liver. In patients with
severely impaired renal function, dosage reduction is recommended.
Although very little data are available, patients with severely
impaired hepatic function may be at greater risk of toxicity (See
Dosage and Administration).
Side Effects
MONOTHERAPY
Adults
The frequency and severity of adverse events associated with the
use of zidovudine in adults are greater in patients with more
advanced infection at the time of initiation of therapy.
The anaemia reported in patients with advanced HIV disease
receiving zidovudine appeared to be the result of impaired
erythrocyte maturation. Thrombocytopenia has also been reported in
patients with advanced disease. Mild drug-associated elevations in
total bilirubin levels have been reported as an uncommon
occurrence in patients treated for asymptomatic HIV infection.
Clinical adverse events or symptoms which occurred in at least 5%
of all patients with advanced HIV disease treated with 1,500
mg/day of zidovudine were: fever, headache, nausea, vomiting,
anorexia, myalgia, insomnia, dizziness, paraesthesia, dyspnoea and
rash. Malaise, gastrointestinal pain, dyspepsia, and taste
perversion were also reported.
Paediatrics
Anaemia and granulocytopenia among paediatric patients with
advanced HIV disease receiving zidovudine occurred with similar
incidence to that reported for adults with AIDS or advanced
AIDS-Related complex. Macrocytosis was frequently observed.
Other adverse events were similar to that observed in adults.
Maternal-Foetal Transmission
The most commonly reported adverse experiences were anaemia and
neutropenia. The long-term consequences of in vitro and infant
exposure to zidovudine are unknown.
Overdosage
No reported cases of acute overdosage (up to 50 gms) in both
children and adults have been
fatal. The consistent finding in these cases was spontaneous or
induced nausea and vomiting. Hematologic changes were transient
and not severe. Hemodialysis and peritoneal dialysis appear to
have a negligible effect on the removal of zidovudine while
elimination of its primary metabolite is enhanced.
Presentation
Zidovir 100
Strip of 10 capsules and container of 100 capsules
Zidovir 300
Strip of 10 tablets and container of 60 tablets
Zidovir
Bottle of 100 ml Oral Solution with syringe
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