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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
ANTIRETROVIRAL 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-retroviral
drug acting against human immunodeficiency virus (HIV).
Indications
Zidovir is indicated for the treatment of HIV
infection when antiretroviral therapy is warranted.
The duration of clinical benefit from antiretroviral
therapy may be limited. Alteration in antiretroviral
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.
Dosage and Administration
The recommended total oral daily dose of Zidovir
is 600 mg per day in divided doses in combination with
other antiretroviral 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 antiretroviral
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
antiretroviral 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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