Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/4168
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Retrovir (Capsule)
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| dailymed-instance:dosage |
Adults: The recommended oral dose of RETROVIR is 600 mg
per day in divided doses in combination with other antiretroviral
agents.<br/>Pediatrics: The recommended dose in pediatric patients 6 weeks
to 12 years of age is 160 mg/mevery 8 hours
(480 mg/m/day up to a maximum of 200 mg every
8 hours) in combination with other antiretroviral agents.<br/>Maternal-Fetal HIV Transmission: The recommended dosing regimen for administration
to pregnant women (>14 weeks of pregnancy) and their neonates
is:<br/>Maternal Dosing: 100 mg
orally 5 times per day until the start of labor (see INDICATIONS
AND USAGE: Description of Clinical Studies). During labor and delivery,
intravenous RETROVIR should be administered at 2 mg/kg (total
body weight) over 1 hour followed by a continuous intravenous
infusion of 1 mg/kg/hour (total body weight) until clamping of
the umbilical cord.<br/>Neonatal Dosing: 2 mg/kg
orally every 6 hours starting within 12 hours after birth
and continuing through 6 weeks of age. Neonates unable to receive
oral dosing may be administered RETROVIR intravenously at 1.5 mg/kg,
infused over 30 minutes, every 6 hours. (See PRECAUTIONS
if hepatic disease or renal insufficiency is present.)<br/>Monitoring of Patients: Hematologic toxicities appear to be related to pretreatment
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 anemia or neutropenia (see WARNINGS).
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.<br/>Dose Adjustment:<br/>Anemia: Significant anemia (hemoglobin of<7.5 g/dL
or reduction of>25% of baseline) and/or significant neutropenia (granulocyte
count of<750 cells/mmor reduction of>50% from
baseline) may require a dose interruption until evidence of marrow
recovery is observed (see WARNINGS). In patients who develop significant
anemia, dose interruption does not necessarily eliminate the need
for transfusion. If marrow recovery occurs following dose interruption,
resumption in dose may be appropriate using adjunctive measures such
as epoetin alfa at recommended doses, depending on hematologic indices
such as serum erythropoetin level and patient tolerance. For patients experiencing pronounced anemia while
receiving chronic coadministration of zidovudine and some of the drugs
(e.g., fluconazole, valproic acid) listed in Table 4, zidovudine dose
reduction may be considered.<br/>End-Stage Renal Disease: In patients maintained on hemodialysis or peritoneal
dialysis, recommended dosing is 100 mg every 6 to 8 hours
(see CLINICAL PHARMACOLOGY: Pharmacokinetics).<br/>Hepatic Impairment: There are insufficient data to recommend dose adjustment
of RETROVIR in patients with mild to moderate impaired hepatic function
or liver cirrhosis. Since RETROVIR is primarily eliminated by hepatic
metabolism, a reduction in the daily dose may be necessary in these
patients. Frequent monitoring for hematologic toxicities is advised
(see CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: General).
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| dailymed-instance:descripti... |
RETROVIR is the brand name for zidovudine (formerly
called azidothymidine [AZT]), a pyrimidine nucleoside analogue active
against HIV.<br/>Tablets: RETROVIR Tablets are for oral administration. Each
film-coated tablet contains 300 mg of zidovudine and the inactive
ingredients hypromellose, magnesium stearate, microcrystalline cellulose,
polyethylene glycol, sodium starch glycolate, and titanium dioxide.<br/>Capsules: RETROVIR Capsules are for oral administration. Each
capsule contains 100 mg of zidovudine and the inactive ingredients
corn starch, magnesium stearate, microcrystalline cellulose, and sodium
starch glycolate. The 100-mg empty hard gelatin capsule, printed with
edible black ink, consists of black iron oxide, dimethylpolysiloxane,
gelatin, pharmaceutical shellac, soya lecithin, and titanium dioxide.<br/>Syrup: RETROVIR Syrup is for oral administration. Each
teaspoonful (5 mL) of RETROVIR Syrup contains 50 mg of zidovudine
and the inactive ingredients sodium benzoate 0.2% (added as a preservative),
citric acid, flavors, glycerin, and liquid sucrose. Sodium hydroxide
may be added to adjust pH. The chemical
name of zidovudine is 3���-azido-3���-deoxythymidine; it
has the following structural formula: Zidovudine is a white to beige, odorless, crystalline
solid with a molecular weight of 267.24 and a solubility of 20.1 mg/mL
in water at 25��C.The molecular
formula is CHNO.
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Pharmacokinetics:<br/>Adults: The pharmacokinetic properties of zidovudine in
fasting patients are summarized in Table 1. Following oral administration,
zidovudineis rapidly absorbed and extensively distributed, with peak
serum concentrations occurring within 0.5 to 1.5 hours. Binding
to plasma protein is low. Zidovudine is primarily eliminated by hepatic
metabolism. The major metabolite of zidovudine is 3���-azido-3���-deoxy-5���-O -��-D-glucopyranuronosylthymidine (GZDV). GZDV area under the
curve (AUC) is about 3-fold greater than the zidovudine AUC. Urinary
recovery of zidovudine and GZDV accounts for 14% and 74%, respectively,
of the dose following oral administration. A second metabolite, 3���-amino-3���-deoxythymidine
(AMT), has been identified in the plasma following single-dose intravenous
(IV) administration of zidovudine. The AMT AUC was one fifth of the
zidovudine AUC. Pharmacokinetics of zidovudine were dose independent
at oral dosing regimens ranging from 2 mg/kg every 8 hours
to 10 mg/kg every 4 hours. The
extent of absorption (AUC) was equivalent when zidovudine was administered
as RETROVIR Tablets or Syrup compared to RETROVIR Capsules. Median [range]. Approximate range.<br/>Adults With Impaired Renal
Function: Zidovudine clearance
was decreased resulting in increased zidovudine and GZDV half-life
and AUC in patients with impaired renal function (n = 14)
following a single 200-mg oral dose (Table 2). Plasma concentrations
of AMT were not determined. A dose adjustment should not be necessary
for patients with creatinine clearance (CrCl)���15 mL/min. Data are expressed
as mean��standard deviation. The pharmacokinetics and tolerance of zidovudine were evaluated
in a multiple-dose study in patients undergoing hemodialysis (n = 5)
or peritoneal dialysis (n = 6) receiving escalating doses
up to 200 mg 5 times daily for 8 weeks. Daily doses
of 500 mg or less were well tolerated despite significantly elevated
GZDV plasma concentrations. Apparent zidovudine oral clearance was
approximately 50% of that reported in patients with normal renal function.
Hemodialysis and peritoneal dialysis appeared to have a negligible
effect on the removal of zidovudine, whereas GZDV elimination was
enhanced. A dosageadjustment is recommended for patients undergoing
hemodialysis or peritoneal dialysis (see DOSAGE AND ADMINISTRATION:
Dose Adjustment).<br/>Adults With Impaired Hepatic
Function: Data
describing the effect of hepatic impairment on the pharmacokinetics
of zidovudine are limited. However, because zidovudine is eliminated
primarily by hepatic metabolism, it is expected that zidovudine clearance
would be decreased and plasma concentrations would be increased following
administration of the recommended adult doses to patients with hepatic
impairment (see DOSAGE AND ADMINISTRATION: Dose Adjustment).<br/>Pediatrics: Zidovudine pharmacokinetics have been evaluated
in HIV-infected pediatric patients (Table 3).<br/>Pregnancy: Zidovudine pharmacokinetics have been studied in
a Phase 1 study of 8 women during the last trimester of pregnancy.
As pregnancy progressed, there was no evidence of drug accumulation.
Zidovudine pharmacokinetics were similar to those of nonpregnant adults.
Consistent with passive transmission of the drug across the placenta,
zidovudine concentrations in neonatal plasma at birth were essentially
equal to those in maternal plasma at delivery. Although data are limited,
methadone maintenance therapy in 5 pregnant women did not appear
to alter zidovudine pharmacokinetics. However, in another patient
population, a potential for interaction has been identified (see PRECAUTIONS).<br/>Nursing Mothers: The Centers for Disease
Control and Prevention recommend that HIV-infected mothers not breastfeed
their infants to avoid risking postnatal transmission of HIV. After administration of a single dose of 200 mg zidovudine
to 13 HIV-infected women, the mean concentration of zidovudine
was similar in human milk and serum (see PRECAUTIONS: Nursing Mothers).<br/>Geriatric Patients: Zidovudine pharmacokinetics have not been studied
in patients over 65 years of age.<br/>Gender: A pharmacokinetic study in healthy male (n = 12)
and female (n = 12) subjects showed no differences in zidovudine
exposure (AUC) when a single dose of zidovudine was administered as
the 300-mg RETROVIR Tablet.<br/>Effect of Food on Absorption: RETROVIR may be administered with or without food.
The extent of zidovudine absorption (AUC) was similar when a single
dose of zidovudine was administered with food.<br/>Drug Interactions: See Table 4 and PRECAUTIONS: Drug Interactions.<br/>Zidovudine Plus Lamivudine: No clinically significant alterations in lamivudine
or zidovudine pharmacokinetics were observed in 12 asymptomatic
HIV-infected adult patients given a single dose of zidovudine (200 mg)
in combination with multiple doses of lamivudine (300 mg every
12 hours). ���= Increase;���= Decrease;���= no significant change; AUC = area
under the concentration versus time curve; CI = confidence interval. This table is not all
inclusive. Estimated range of percent difference.<br/>Ribavirin: In vitro data indicate ribavirin reduces phosphorylation
of lamivudine, stavudine, and zidovudine. However, no pharmacokinetic
(e.g., plasma concentrations or intracellular triphosphorylated active
metabolite concentrations) or pharmacodynamic (e.g., loss of HIV/HCV
virologic suppression) interaction was observed when ribavirin and
lamivudine (n = 18), stavudine (n = 10), or zidovudine
(n = 6) were co-administered as part of a multi-drug regimen
to HIV/HCV co-infected patients (see WARNINGS).
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RETROVIR Tablets, Capsules, and Syrup are contraindicated
for patients who have potentially life-threatening allergic reactions
to any of the components of the formulations.
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| dailymed-instance:supply |
RETROVIR Tablets 300 mg (biconvex, white,
round, film-coated) containing 300 mg zidovudine, one side engraved���GX CW3���and���300���on the other side. Bottle of 60 (NDC 0173-0501-00). Store at 15��to 25��C (59��to 77��F). RETROVIR Capsules
100 mg (white, opaque cap and body) containing 100 mg zidovudine
and printed with���Wellcome���and unicorn logo on cap
and���Y9C���and���100���on body. Bottles of 100 (NDC 0173-0108-55). Unit Dose Pack of 100 (NDC 0173-0108-56). Store at 15��to 25��C (59��to 77��F) and protect from moisture. RETROVIR Syrup (colorless to pale yellow, strawberry-flavored)
containing 50 mg zidovudine in each teaspoonful (5 mL). Bottle of 240 mL (NDC 0173-0113-18) with child-resistant
cap. Store at 15��to 25��C (59��to 77��F). GlaxoSmithKline Research Triangle Park, NC
27709 ��2006, GlaxoSmithKline. All rights
reserved. November 2006RL-2325
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WARNING: RETROVIR (ZIDOVUDINE) HAS
BEEN ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING NEUTROPENIA AND
SEVERE ANEMIA PARTICULARLY IN PATIENTS WITH ADVANCED HUMAN IMMUNODEFICIENCY
VIRUS (HIV) DISEASE (SEE WARNINGS). PROLONGED USE OF RETROVIR HAS
BEEN ASSOCIATED WITH SYMPTOMATIC MYOPATHY. LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY
WITH STEATOSIS, INCLUDING FATAL CASES, HAVE BEEN REPORTED WITH THE
USE OF NUCLEOSIDE ANALOGUES ALONE OR IN COMBINATION, INCLUDING RETROVIR
AND OTHER ANTIRETROVIRALS (SEE WARNINGS).
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| dailymed-instance:inactiveI... |
dailymed-ingredient:FD&C_Blue_No._2,
dailymed-ingredient:black_iron_oxide,
dailymed-ingredient:corn_starch,
dailymed-ingredient:dimethylpolysiloxane,
dailymed-ingredient:gelatin,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:pharmaceutical_shellac,
dailymed-ingredient:sodium_starch_glycolate,
dailymed-ingredient:soya_lecithin,
dailymed-ingredient:titanium_dioxide
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| dailymed-instance:precautio... |
General: Zidovudine is eliminated from the body primarily
by renal excretion following metabolism in the liver (glucuronidation).
In patients with severely impaired renal function (CrCl<15 mL/min),
dosage reduction is recommended. Although the data are limited, zidovudine
concentrations appear to be increased in patients with severely impaired
hepatic function which may increase the risk of hematologic toxicity
(see CLINICAL PHARMACOLOGY: Pharmacokinetics and DOSAGE AND ADMINISTRATION).<br/>Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported
in patients treated with combination antiretroviral therapy, including
RETROVIR. During the initial phase of combination antiretroviral treatment,
patients whose immune system responds may develop an inflammatory
response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP],
or tuberculosis), which may necessitate further evaluation and treatment.<br/>Fat Redistribution: Redistribution/accumulation of body fat, including
central obesity, dorsocervical fat enlargement (buffalo hump), peripheral
wasting, facial wasting, breast enlargement, and���cushingoid
appearance,���have been observed in patients receiving antiretroviral
therapy. The mechanism and long-term consequences of these events
are currently unknown. A causal relationship has not been established.<br/>Information for Patients: RETROVIR is not a cure for HIV infection, and patients
may continue to acquire illnesses associated with HIV infection, including
opportunistic infections. Therefore, patients should be advised to
seek medical care for any significant change in their health status. The safety and efficacy of RETROVIR in women, intravenous
drug users, and racial minorities is not significantly different than
that observed in white males. Patients should
be informed that the major toxicities of RETROVIR are neutropenia
and/or anemia. The frequency and severity of these toxicities are
greater in patients with more advanced disease and in those who initiate
therapy later in the course of their infection. They should be told
that if toxicity develops, they may require transfusions or drug discontinuation.
They should be told of the extreme importance of having their blood
counts followed closely while on therapy, especially for patients
with advanced symptomatic HIV disease. They should be cautioned about
the use of other medications, including ganciclovir and interferon
alfa, which may exacerbate the toxicity of RETROVIR (see PRECAUTIONS:
Drug Interactions). Patients should be informed that other adverse
effects of RETROVIR include nausea and vomiting. Patients should also
be encouraged to contact their physician if they experience muscle
weakness, shortness of breath, symptoms of hepatitis or pancreatitis,
or any other unexpected adverse events while being treated with RETROVIR. RETROVIR Tablets, Capsules, and Syrup are for oral
ingestion only. Patients should be told of the importance of taking
RETROVIR exactly as prescribed. They should be told not to share medication
and not to exceed the recommended dose. Patients should be told that
the long-term effects of RETROVIR are unknown at this time. Pregnant women considering the use of RETROVIR during
pregnancy for prevention of HIV transmission to their infants should
be advised that transmission may still occur in some cases despite
therapy. The long-term consequences of in utero and infant exposure
to RETROVIR are unknown, including the possible risk of cancer. HIV-infected pregnant women should be advised not
to breastfeed to avoid postnatal transmission of HIV to a child who
may not yet be infected. Patients should
be advised that therapy with RETROVIR has not been shown to reduce
the risk of transmission of HIV to others through sexual contact or
blood contamination. Patients should be
informed that redistribution or accumulation of body fat may occur
in patients receiving antiretroviral therapy and that the cause and
long-term health effects of these conditions are not known at this
time.<br/>Drug Interactions: See CLINICAL PHARMACOLOGY section (Table 4) for
information on zidovudine concentrations when coadministered with
other drugs. For patients experiencing pronounced anemia or other
severe zidovudine-associated events while receiving chronic administration
of zidovudine and some of the drugs (e.g., fluconazole, valproic acid)
listed in Table 4, zidovudine dose reduction may be considered.<br/>Antiretroviral Agents: Concomitant use
of zidovudine with stavudine should be avoided since an antagonistic
relationship has been demonstrated in vitro. Some nucleoside analogues affecting DNA replication, such as
ribavirin, antagonize the in vitro antiviral activity of RETROVIR
against HIV; concomitant use of such drugs should be avoided.<br/>Doxorubicin: Concomitant use of zidovudine with doxorubicin should
be avoided since an antagonistic relationship has been demonstrated
in vitro (see CLINICAL PHARMACOLOGY for additional drug interactions).<br/>Phenytoin: Phenytoin plasma levels have been reported to be
low in some patients receiving RETROVIR, while in one case a high
level was documented. However, in a pharmacokinetic interaction study
in which 12 HIV-positive volunteers received a single 300-mg
phenytoin dose alone and during steady-state zidovudine conditions
(200 mg every 4 hours), no change in phenytoin kinetics
was observed. Although not designed to optimally assess the effect
of phenytoin on zidovudine kinetics, a 30% decrease in oral zidovudine
clearance was observed with phenytoin.<br/>Overlapping Toxicities: Coadministration of ganciclovir, interferon alfa,
and other bone marrow suppressive or cytotoxic agents may increase
the hematologic toxicity of zidovudine.<br/>Carcinogenesis, Mutagenesis,
Impairment of Fertility: Zidovudinewas
administered orally at 3 dosage levels to separate groups of
mice and rats (60 females and 60 males in each group). Initial
single daily doses were 30, 60, and 120 mg/kg/day in mice and
80, 220, and 600 mg/kg/day in rats. The doses in mice were reduced
to 20, 30, and 40 mg/kg/day after day 90 because of treatment-related
anemia, whereas in rats only the high dose was reduced to 450 mg/kg/day
on day 91 and then to 300 mg/kg/day on day 279. In mice, 7 late-appearing (after 19 months)
vaginal neoplasms (5 nonmetastasizing squamous cell carcinomas,
1 squamous cell papilloma, and 1 squamous polyp) occurred
in animals given the highest dose. One late-appearing squamous cell
papilloma occurred in the vagina of a middle-dose animal. No vaginal
tumors were found at the lowest dose. In
rats, 2 late-appearing (after 20 months), nonmetastasizing
vaginal squamous cell carcinomas occurred in animals given the highest
dose. No vaginal tumors occurred at the low or middle dose in rats.
No other drug-related tumors were observed in either sex of either
species. At doses that produced tumors in
mice and rats, the estimated drug exposure (as measured by AUC) was
approximately 3 times (mouse) and 24 times (rat) the estimated
human exposure at the recommended therapeutic dose of 100 mg
every 4 hours. Two transplacental carcinogenicity
studies were conducted in mice. One study administered zidovudine
at doses of 20 mg/kg/day or 40 mg/kg/day from gestation
day 10 through parturition and lactation with dosing continuing in
offspring for 24 months postnatally. The doses of zidovudine
employed in this study produced zidovudine exposures approximately
3 times the estimated human exposure at recommended doses. After
24 months, an increase in incidence of vaginal tumors was noted
with no increase in tumors in the liver or lung or any other organ
in either gender. These findings are consistent with results of the
standard oral carcinogenicity study in mice, as described earlier.
A second study administered zidovudine at maximum tolerated doses
of 12.5 mg/day or 25 mg/day (���1,000 mg/kg nonpregnant
body weight or���450 mg/kg of term body weight) to pregnant
mice from days 12 through 18 of gestation. There was an increase in
the number of tumors in the lung, liver, and female reproductive tracts
in the offspring of mice receiving the higher dose level of zidovudine. It is not known how predictive the results of rodent
carcinogenicity studies may be for humans. Zidovudine
was mutagenic in a 5178Y/TKmouse lymphoma assay, positive
in an in vitro cell transformation assay, clastogenic in a cytogenetic
assay using cultured human lymphocytes, and positive in mouse and
rat micronucleus tests after repeated doses. It was negative in a
cytogenetic study in rats given a single dose. Zidovudine, administered to male and female rats at doses up
to 7 times the usual adult dose based on body surface area considerations,
had no effect on fertility judged by conception rates.<br/>Pregnancy: Pregnancy Category C. Oral teratology studies in
the rat and in the rabbit at doses up to 500 mg/kg/day revealed
no evidence of teratogenicity with zidovudine. Zidovudine treatment
resulted in embryo/fetal toxicity as evidenced by an increase in the
incidence of fetal resorptions in rats given 150 or 450 mg/kg/day
and rabbits given 500 mg/kg/day. The doses used in the teratology
studies resulted in peak zidovudine plasma concentrations (after one
half of the daily dose) in rats 66 to 226 times, and in rabbits
12 to 87 times, mean steady-state peak human plasma concentrations
(after one sixth of the daily dose) achieved with the recommended
daily dose (100 mg every 4 hours). In an in vitro experiment
with fertilized mouse oocytes, zidovudine exposure resulted in a dose-dependent
reduction in blastocyst formation. In an additional teratology study
in rats, a dose of 3,000 mg/kg/day (very near the oral median
lethal dose in rats of 3,683 mg/kg) caused marked maternal toxicity
and an increase in the incidence of fetal malformations. This dose
resulted in peak zidovudine plasma concentrations 350 times peak
human plasma concentrations. (Estimated area under the curve [AUC]
in rats at this dose level was 300 times the daily AUC in humans
given 600 mg/day.) No evidence of teratogenicity was seen in
this experiment atdoses of 600 mg/kg/day or less. Two rodent transplacental carcinogenicity studies
were conducted (see Carcinogenesis, Mutagenesis, Impairment of Fertility). A randomized, double-blind, placebo-controlled trial
was conducted in HIV-infected pregnant women to determine the utility
of RETROVIR for the prevention of maternal-fetal HIV-transmission
(see INDICATIONS AND USAGE: Description of Clinical Studies). Congenital
abnormalities occurred with similar frequency between neonates born
to mothers who received RETROVIR and neonates born to mothers who
received placebo. Abnormalities were either problems in embryogenesis
(prior to 14 weeks) or were recognized on ultrasound before or
immediately after initiation of study drug.<br/>Antiretroviral Pregnancy Registry: To monitor
maternal-fetal outcomes of pregnant women exposed to RETROVIR, an
Antiretroviral Pregnancy Registry has been established. Physicians
are encouraged to register patients by calling 1-800-258-4263.<br/>Nursing Mothers: The Centers for Disease
Control and Prevention recommend that HIV-infected mothers not breastfeed
their infants to avoid risking postnatal transmission of HIV. Zidovudine is excreted in human milk (see CLINICAL PHARMACOLOGY:
Pharmacokinetics: Nursing Mothers). Because of both the potential
for HIV transmission and the potential for serious adverse reactions
in nursing infants, mothers should be instructed
not to breastfeed if they are receiving RETROVIR (see Pediatric
Use and INDICATIONS AND USAGE: Maternal-Fetal HIV Transmission).<br/>Pediatric Use: RETROVIR has been studied in HIV-infected pediatric
patients over 3 months of age who had HIV-related symptoms or
who were asymptomatic with abnormal laboratory values indicating significant
HIV-related immunosuppression. RETROVIR has also been studied in neonates
perinatally exposed to HIV (see ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION,
INDICATIONS AND USAGE: Description of Clinical Studies, and CLINICAL
PHARMACOLOGY: Pharmacokinetics).<br/>Geriatric Use: Clinical studies of RETROVIR did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond
differently from younger subjects. Other reported clinical experience
has not identified differences in responses between the elderly and
younger patients. In general, dose selection for an elderly patient
should be cautious, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or
other drug therapy.
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| dailymed-instance:overdosag... |
Acute overdoses
of zidovudine have been reported in pediatric patients and adults.
These involved exposures up to 50 grams. No specific symptoms
or signs have been identified following acute overdosage with zidovudine
apart from those listed as adverse events such as fatigue, headache,
vomiting, and occasional reports of hematological disturbances.All patients recovered without permanent
sequelae. Hemodialysis and peritoneal dialysis appear to have a negligible
effect on the removal of zidovudine while elimination of its primary
metabolite, GZDV, is enhanced.
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| dailymed-instance:genericMe... |
zidovudine
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| dailymed-instance:fullName |
Retrovir (Capsule)
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| dailymed-instance:adverseRe... |
Adults: The frequency and severity of adverse events associated
with the use of RETROVIR are greater in patients with more advanced
infection at the time of initiation of therapy. Table 6 summarizes events reported at a statistically significant
greater incidence for patients receiving RETROVIR in a monotherapy
study: Reported in���5%
of study population. Not statistically significant versus placebo. In addition to the adverse events listed in Table
6, other adverse events observed in clinical studies were abdominal
cramps, abdominal pain, arthralgia, chills, dyspepsia, fatigue, hyperbilirubinemia,
insomnia, musculoskeletal pain, myalgia, and neuropathy. Selected laboratory abnormalities observed during
a clinical study of monotherapy with RETROVIR are shown in Table 7. ULN = Upper limit
of normal.<br/>Pediatrics:<br/>Study ACTG300: Selected
clinical adverse events and physical findings with a���5% frequency
during therapy with EPIVIR 4 mg/kg twice daily plus RETROVIR
160 mg/m3 times daily compared with didanosine
in therapy-naive (���56 days of antiretroviral therapy)
pediatric patients are listed in Table 8. Includes pain,
discharge, erythema, or swelling of an ear. Selected laboratory abnormalities experienced by therapy-naive
(���56 days of antiretroviral therapy) pediatric patients
are listed in Table 9. ULN = Upper limit
of normal. ANC = Absolute
neutrophil count. Additional adverse events
reported in open-label studies in pediatric patients receiving RETROVIR
180 mg/mevery 6 hours were congestive heart
failure, decreased reflexes, ECG abnormality, edema, hematuria, left
ventricular dilation, macrocytosis, nervousness/irritability, and
weight loss. The clinical adverse events
reported among adult recipients of RETROVIR may also occur in pediatric
patients.<br/>Use for the Prevention of
Maternal-Fetal Transmission of HIV: In a randomized, double-blind, placebo-controlled
trial in HIV-infected women and their neonates conducted to determine
the utility of RETROVIR for the prevention of maternal-fetal HIV transmission,
RETROVIR Syrup at 2 mg/kg was administered every 6 hours
for 6 weeks to neonates beginning within 12 hours following
birth. The most commonly reported adverse experiences were anemia
(hemoglobin<9.0 g/dL) and neutropenia (<1,000 cells/mm). Anemia occurred in 22% of the neonates who received RETROVIR
and in 12% of the neonates who received placebo. The mean difference
in hemoglobin values was less than 1.0 g/dL for neonates receiving
RETROVIR compared to neonates receiving placebo. No neonates with
anemia required transfusion and all hemoglobin values spontaneously
returned to normal within 6 weeks after completion of therapy
with RETROVIR. Neutropenia was reported with similar frequency in
the group that received RETROVIR (21%) and inthe group that received
placebo (27%). The long-term consequences of in uteroand infant exposure to RETROVIR are
unknown.<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical
trials, the following events have been identified during use of RETROVIR
in clinical practice. Because they are reported voluntarily from a
population of unknown size, estimates of frequency cannot be made.
These events have been chosen for inclusion due to either their seriousness,
frequency of reporting, potential causal connection to RETROVIR, or
a combination of these factors.<br/>Body as a Whole: Back
pain, chest pain, flu-like syndrome, generalized pain, redistribution/accumulation
of body fat (see PRECAUTIONS: Fat Redistribution).<br/>Cardiovascular: Cardiomyopathy, syncope.<br/>Endocrine: Gynecomastia.<br/>Eye: Macular edema.<br/>Gastrointestinal: Constipation,
dysphagia, flatulence, oral mucosa pigmentation, mouth ulcer.<br/>General: Sensitization reactions including anaphylaxis and
angioedema, vasculitis.<br/>Hemic and Lymphatic: Aplastic anemia,
hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia with marrow
hypoplasia, pure red cell aplasia.<br/>Hepatobiliary Tract and Pancreas: Hepatitis, hepatomegaly with steatosis, jaundice,
lactic acidosis, pancreatitis.<br/>Musculoskeletal: Increased CPK, increased LDH, muscle spasm, myopathy
and myositis with pathological changes (similar to that produced by
HIV disease), rhabdomyolysis, tremor.<br/>Nervous: Anxiety, confusion,
depression, dizziness, loss of mental acuity, mania, paresthesia,
seizures, somnolence, vertigo.<br/>Respiratory: Cough, dyspnea,
rhinitis, sinusitis.<br/>Skin: Changes in skin
and nail pigmentation, pruritus, rash, Stevens-Johnson syndrome, toxic
epidermal necrolysis, sweat, urticaria.<br/>Special Senses: Amblyopia, hearing
loss, photophobia, taste perversion.<br/>Urogenital: Urinary frequency, urinary hesitancy.
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COMBIVIRand TRIZIVIR are combination product tablets that contain zidovudine as one of
their components. RETROVIR should not be administered concomitantly
with COMBIVIR or TRIZIVIR. The incidence
of adverse reactions appears to increase with disease progression;
patients should be monitored carefully, especially as disease progression
occurs.<br/>Bone Marrow Suppression: RETROVIR should be used with caution in patients
who have bone marrow compromise evidenced by granulocyte count<1,000 cells/mmor hemoglobin<9.5 g/dL. In patients with advanced
symptomatic HIV disease, anemia and neutropenia were the most significant
adverse events observed. There have been reports of pancytopenia associated
with the use of RETROVIR, which was reversible in most instances after
discontinuance of the drug. However, significant anemia, in many cases
requiring dose adjustment, discontinuation of RETROVIR, and/or blood
transfusions, has occurred during treatment with RETROVIR alone or
in combination with other antiretrovirals. Frequent
blood counts are strongly recommended in patients with advanced HIV
disease who are treated with RETROVIR. For HIV-infected individuals
and patients with asymptomatic or early HIV disease, periodic blood
counts are recommended. If anemia or neutropenia develops, dosage
adjustments may be necessary (see DOSAGE AND ADMINISTRATION).<br/>Myopathy: Myopathy and myositis with pathological changes,
similar to that produced by HIV disease, have been associated with
prolonged use of RETROVIR.<br/>Lactic Acidosis/Severe Hepatomegaly
with Steatosis: Lactic acidosis and severe hepatomegaly with steatosis,
including fatal cases, have been reported with the use of nucleoside
analogues alone or in combination, including zidovudine and other
antiretrovirals. A majority of these cases have been in women. Obesity
and prolonged exposure to antiretroviral nucleoside analogues may
be risk factors. Particular caution should be exercised when administering
RETROVIR to any patient with known risk factors for liver disease;
however, cases have also been reported in patients with no known risk
factors. Treatment with RETROVIR should be suspended in any patient
who develops clinical or laboratory findings suggestive of lactic
acidosis or pronounced hepatotoxicity (which may include hepatomegaly
and steatosis even in the absence of marked transaminase elevations).<br/>Use With Interferon- and Ribavirin-Based
Regimens: In vitro studies have shown ribavirin can reduce
the phosphorylation of pyrimidine nucleoside analogues such as zidovudine.
Although no evidence of a pharmacokinetic or pharmacodynamic interaction
(e.g., loss of HIV/HCV virologic suppression) was seen when ribavirin
was coadministered with zidovudine in HIV/HCV co-infected patients
(see CLINICAL PHARMACOLOGY: Drug Interactions), hepatic decompensation (some fatal) has occurred in HIV/HCV co-infected
patients receiving combination antiretroviral therapy for HIV and
interferon alfa with or without ribavirin. Patients receiving
interferon alfa with or without ribavirin and RETROVIR should be closely
monitored for treatment-associated toxicities, especially hepatic
decompensation, neutropenia, and anemia. Discontinuation of RETROVIR
should be considered as medically appropriate. Dose reduction or discontinuation
of interferon alfa, ribavirin, or both should also be considered if
worsening clinical toxicities are observed, including hepatic decompensation
(e.g., Childs Pugh>6) (see the complete prescribing information for
interferon and ribavirin).
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| dailymed-instance:indicatio... |
RETROVIR in combination
with other antiretroviral agentsis indicated for the treatment of HIV infection.<br/>Maternal-Fetal HIV Transmission: RETROVIR
is also indicated for the prevention of maternal-fetal HIV transmission
as part of a regimen that includes oral RETROVIR beginning between
14 and 34 weeks of gestation, intravenous RETROVIR during labor,
and administration of RETROVIR Syrup to the neonate after birth. The
efficacy of this regimen for preventing HIV transmission in women
who have received RETROVIR for a prolonged period before pregnancy
has not been evaluated.Thesafety of RETROVIR for the mother or fetus
during the first trimester of pregnancy has not been assessed (see
Description of Clinical Studies).<br/>Description of Clinical Studies: Therapy with RETROVIR has been shown to prolong survival
and decrease the incidence of opportunistic infections in patients
with advanced HIV disease and to delay disease progression in asymptomaticHIV-infected patients.<br/>Combination Therapy in Adults: RETROVIR in combination with other antiretroviral
agents has been shown to be superior to monotherapy for one or more
of the following endpoints: delaying death, delaying development of
AIDS, increasing CD4+ cell counts, and decreasing plasma HIV-1 RNA.
The clinical efficacy of a combination regimen that includes RETROVIR
was demonstrated in study ACTG320. This study was a multi-center,
randomized, double-blind, placebo-controlled trial that compared RETROVIR
600 mg/day plus EPIVIR 300 mg/day to RETROVIR
plus EPIVIR plus indinavir 800 mg t.i.d. The incidence of AIDS-defining
events or death was lower in the triple-drug���containing arm
compared to the 2-drug���containing arm (6.1% versus 10.9%, respectively). The complete prescribing information for each drug
should be consulted before combination therapy that includes RETROVIR
is initiated.<br/>Monotherapy in Adults: In controlled studies of treatment-naive patients
conducted between 1986 and 1989, monotherapy with RETROVIR, as compared
to placebo, reduced the risk of HIV disease progression, as assessed
using endpoints that included the occurrence of HIV-related illnesses,
AIDS-defining events, or death. These studies enrolled patients with
advanced disease (BW002), and asymptomatic or mildly symptomatic disease
in patients with CD4+ cell counts between 200 and 500 cells/mm(ACTG016 and ACTG019). A survival benefit for monotherapy
with RETROVIR was not demonstrated in the latter 2 studies. Subsequent
studies showed that the clinical benefit of monotherapy with RETROVIR
was time limited.<br/>Pediatric Patients: ACTG300 was a multi-center, randomized, double-blind
study that provided for comparison of EPIVIR plus RETROVIR to didanosine
monotherapy. A total of 471 symptomatic, HIV-infected therapy-naive
pediatric patients were enrolled in these 2 treatment arms. The
median age was 2.7 years (range 6 weeks to 14 years),
the mean baseline CD4+ cell count was 868 cells/mm, and the mean baseline plasma HIV-1 RNA was 5.0 logcopies/mL. The median duration that patients remained on study was
approximately 10 months. Results are summarized in Table 5.<br/>Pregnant Women and Their Neonates: The utility of RETROVIR for the prevention of maternal-fetal
HIV transmission was demonstrated in a randomized, double-blind, placebo-controlled
trial (ACTG076) conducted in HIV-infected pregnant women with CD4+
cell counts of 200 to 1,818 cells/mm(median in the
treated group: 560 cells/mm) who had little or no
previous exposure to RETROVIR. Oral RETROVIR was initiated between
14 and 34 weeks of gestation (median 11 weeks of therapy)
followed by IV administration of RETROVIR during labor and delivery.
Following birth, neonates received oral RETROVIR Syrup for 6 weeks.
The study showed a statistically significant difference in the incidence
of HIV infection in the neonates (based on viral culture from peripheral
blood) between the group receiving RETROVIR and the group receiving
placebo. Of 363 neonates evaluated in the study, the estimated
risk of HIV infection was 7.8% in the group receiving RETROVIR and
24.9% in the placebo group, a relative reduction in transmission risk
of 68.7%. RETROVIR was well tolerated by mothers and infants. There
was no difference in pregnancy-related adverse events between the
treatment groups.
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| dailymed-instance:name |
Retrovir
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