Warning
ZIDOVUDINE, ONE OF THE TWO ACTIVE INGREDIENTS IN DUOVIR,
HAS BEEN ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING
NEUTROPENIA AND SEVERE ANEMIA, PARTICULARLY IN PATIENTS
WITH ADVANCED HIV DISEASE (See Warnings and Precautions).
PROLONGED USE OF ZIDOVUDINE 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
LAMIVUDINE, ZIDOVUDINE, AND OTHER
ANTIRETROVIRALS (See Warnings and Precautions)
Composition
Each film-coated tablet contains
Lamivudine 150 mg and
Zidovudine USP 300 mg
Description
Duovir is a combination of two drugs commonly used
in the management of Human Immunodeficiency Virus (HIV)
infection. Both lamivudine and zidovudine belong to the
nucleoside analogue class of antiretroviral drugs. Both
drugs act by inhibiting the reverse transcriptase enzyme
of HIV, and by terminating the growth of the DNA chain.
Lamivudine in combination with zidovudine has been shown
to have synergistic antiretroviral activity.
Each tablet of Duovir contains half of the commonly
prescribed daily doses of both lamivudine and zidovudine.
With the availability of this combination tablet, patients
may be better able to adhere to complex drug treatment
regimens, thereby enhancing compliance.
Indications
Duovir is indicated for the treatment of HIV infection.
Dosage and Administration
The recommended oral dose of Duovir for adults
and adolescents (at least 12 years of age) is one tablet
(containing 150 mg of lamivudine and 300 mg of zidovudine)
twice daily with or without food.
Dose Adjustment: Because it is a fixed dose combination,
Duovir should not be prescribed for patients requiring
dosage adjustment such as those with reduced renal function
(creatinine clearance < 50 mL/min), those with low
body weight (< 50 kg or 110 lb), or those experiencing
dose-limiting adverse events.
Contraindications
Duovir tablets are contraindicated in patients
with previously demonstrated clinically significant hypersensitivity
to any of the components of the product.
Warnings and Precautions
Since Duovir is a fixed-dose combination of lamivudine
and zidovudine, it should ordinarily not be administered
concomitantly with either lamivudine or zidovudine.
The complete prescribing information for all agents being
considered for use with Duovir should be consulted
before combination therapy with Duovir is initiated.
BONE MARROW SUPPRESSION
Duovir should be used with caution in patients
who have bone marrow compromise evidenced by granulocyte
count <1,000 cells/mm3 or hemoglobin < 9.5 g/dl
(See Side Effects).
Frequent blood counts are strongly recommended in patients
with advanced HIV disease who are treated with Duovir.
For HIV-infected individuals and patients with asymptomatic
or early HIV disease, periodic blood counts are recommended.
LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS
Lactic acidosis and severe hepatomegaly with steatosis,
including fatal cases, have been reported with the use
of antiretroviral nucleoside analogues alone or in combination,
including zidovudine and lamivudine. A majority of these
cases have been in women. Caution should be exercised
when administering Duovir to any patient, and particularly
to those with known risk factors for liver disease. Treatment
with Duovir should be suspended in any patient
who develops clinical or laboratory findings suggestive
of lactic acidosis or hepatotoxicity.
MYOPATHY
Myopathy and myositis, with pathological changes similar
to that produced by HIV disease, have been associated
with prolonged use of zidovudine and therefore may occur
with therapy with Duovir.
PATIENTS WITH HIV AND HEPATITIS B VIRUS COINFECTION
In clinical trials and postmarketing experience, some
patients with HIV infection who have chronic liver disease
due to hepatitis B virus infection experienced clinical
or laboratory evidence of recurrent hepatitis upon discontinuation
of lamivudine. Consequences may be more severe in patients
with decompensated liver disease.
DRUG INTERACTIONS
Coadministration of ganciclovir, interferon- , and other
bone marrow suppressive or cytotoxic agents may increase
the hematologic toxicity of zidovudine.
IMPAIRED RENAL FUNCTION
Reduction of the dosages of lamivudine and zidovudine
is recommended for patients with impaired renal function.
Patients with creatinine clearance < 50 ml/min should
not receive Duovir.
PREGNANCY
Category C. There are no adequate and well-controlled
studies of this combination in pregnant women. Duovir
should be used during pregnancy only if the potential
benefits outweigh the risks.
LACTATION
It is recommended that HIV-infected mothers not breast-feed
their infants to avoid risking postnatal transmission
of HIV infection.
Zidovudine is excreted in breast milk. No data are available
on this combination or lamivudine. Therefore, there is
a potential for adverse effects in nursing infants. Mothers
should be instructed not to breast-feed if they are receiving
Duovir.
PAEDIATRIC USE
Duovir should not be administered to paediatric
patients less than 12 years of age because it is a fixed-dose
combination that cannot be adjusted for this patient population.
OTHERS
Reduction of doses of lamivudine is recommended for patients
with low body weight (less than 50 kg or 110 lb). Therefore
patients with low body weight should not receive Duovir.
Side Effects
The most commonly observed side effects during clinical
trials were headache, malaise and fatigue, nausea, vomiting,
diarrhoea, anorexia, fever/chills, neuropathy, insomnia,
dizziness, nasal signs and symptoms, cough, musculoskeletal
pain and neutropenia.
Overdosage
There is no known antidote for Duovir.
Lamivudine: One case of an adult ingesting 6 gms
of lamivudine has been reported. There were no clinical
signs or symptoms noted and hematologic tests remained
normal. It is not known whether lamivudine can be removed
by peritoneal dialysis or hemodialysis.
Zidovudine: Acute overdoses of zidovudine have
been reported in paediatric patients and adults. These
involved exposures up to 50 grams. The only consistent
findings were nausea and vomiting. Other reported occurrences
included headache, dizziness, drowsiness, lethargy, confusion,
and one report of a grand mal seizure. Hematologic changes
were transient. All patients recovered. Hemodialysis and
peritoneal dialysis appear to have a negligible effect
on the removal of zidovudine, while elimination of its
primary metabolite is enhanced.
Presentation
Duovir
Blister pack of 10 tablets and
Container of 60 tablets |
