VIROPIL
PRESCRIBING INFORMATION
Viropil is
used adults patients weighing more than 40kg who suffering from human
immunodeficiency virus (HIV) infection.
MECHANISM
Dolutegravir: The drug belongs to class of HIV-1 antiviral
agent. It prevents HIV integrase while bounding to the integrase active
site and stops the strand transfer step of DNA synthesis which is specific for
HIV replication cycle. Strand which transfers biochemical assays using
rectified HIV-1 integrase and pre-processed substrate DNA resulted in IC values
of 2.7nM and 12.6nM.
Tenofovir DF: Tenofovir DF is performs a nasty to viral action
by threatening the turn around transcriptase aggregate by battling with regular
substrate deoxyadenosine 5' triphosphate and after addition into DNA, by viral
DNA chain eliminator.
Tenofovir is used to stoppage the viral DNA synthesis which is a
require for the process of chain elimination.
Lamivudine, belongs to the class of nucleoside synthetic
analogue.
Lamivudine which is phosphorylated intracellularly into active 5’ triphosphate
metabolite (lamivudine triphosphate 3TC-TP.
This active metabolite involves in prevention of reverse
transcriptase via chain termination after infusion of nucleotide analogue
ABSORPTION
The maximum plasma concentration of Dolutegravir is 2 to 3 hrs.
Tenofovir DF : 1hr plus/minus 0.4hrs and bioavailability is 25%
Lamivudine : 1.5± 0.5mcg/ml.
Bioavailability of Lamivudine is 80-87%
DISTRIBUTION
Protein binding for Dolutegravir ,Tenofovir, Lamivudine is
98.9%, <0.7-7.2% and 36%.
METABOLISM
Dolutegravir is primarily metabolized through UGT1A1 with some
contribution from CYP3A
Tenofovir occurs metabolized at cytochrome P450 enzyme
where as Lamivudine is metabolized has trans sulfoxide and the
biotransformation is catalyzed by sulfotrnsferases.
EXCRETION
Dolutegravir
unchanged form is excreted via feces is 53% and urine 31%, Lamivudine excreted
by urine 5.2% ± 1.4% via trans-sulfoxide metabolite
Terminal
half life of Dolutegravir is 14 hrs, Tenofovir DF is 17 hours and Lamivudine is
5 to 7 hours.
WHEN TO TAKE THE DRUG
Piror
to start the treatment with Viropil,
Patient should be monitored for presence of HBV infection or not.
kidney
function & hepatic function test should be performed.
The
usual dose of Viropil
is one tablet of Dolutegravir 50mg, Tenofovir DF 300mg, Lamivudine 300mg should
be administered as once daily.
The
drug is administered on an empty stomach.
Due
to reducing the neurological problems. this tablet should be take at bed time.
DOSAGE REGIMENS
The viropil prescribed
dose is one tablet of dolutegravir 50mg+ lamivudine 300mg + tenofovir DF 300mg
administrated for once in a day.
Renal impairment:
Dosage
adjustment is needed for patients with baseline creatinine clearance
<50-mL/min.
Hepatic impairment:
while
patients with mild to moderate liver impairment has no dosage adjustment is
required.
Pediatric Use: use in that patients is not indicated by FDC
Geriatric use: for the elderly patients should be used with cautions.
DRUG CAUSED SIDE EFFECTS
Lactic
acidosis
Aggravation
of HBV
Renal
damage
Psychiatric
problems
Nervous
problems
Skin
related problems
Liver
toxicity
Hepatic
decompensated cirrhosis
Pancreatitis
Bone
defects
Immune
reconstitution syndrome
Redistribution
of fat
The
most common side effects;
Headache,
pain, fever, abdominal pain, back pain, asthenia, diarrhea, nausea, dyspepsia,
vomiting, lipodystrophy, arthralgia, insomnia
Lab
abnormalities;
Increased
cholesterol, elevation of creatine kinase, increased AST & ALT, Hematuria,
neutropenia, increased serum amylase
DRUG- DRUG INTERACTION
1. Viropil with CYP3A inducers causes increased
clearance of Viropil & leads to reduce the plasma concentration.
2. Viropil with warfarin causes fluctuation in
prothrombin time & INR values.
4. Viropil with anti-fungals, anti-depressants,
or anti-infective causes reduced effect of concentration of these drugs.
5. Viropil with anti-malarial, anti-mycobacterials,
calcium channel blockers, or lipid lowering drugs causes decreased effect of
concentration of these drugs.
6. When interaction with metformin or dofetilide
will cause the plasma concentration of these drugs are increased.
FOOD DRUG INTERACTION
Concomitant
use of Dolutegravir with mineral or vitamin containing substances, it may cause
to increase the ion content, and this alteration intercedes with absorption of
Dolutegravir and depletes the effectiveness.
A
minor food drug interaction occurs.
Diet
should be maintained only after getting advice from the medical adviser.
Common
foods;
Grape
fruit or juice
Seville
orange
Vitamin
E, C containing foods
Garlic
Calcium
supplements
CONTRAINDICATIONS
Hypersensitivity
reaction occurs in patients
Concomitant
use with Dofetilide
SAFETY MEASURES
Severe hepatomegaly with staetosis / Lactic acidosis : While use of nucleoside analogues
involves Lamivudine alone or in combination will causes harm to fetal. Use
Lamivudine with caution in patients having liver disease with known factor
New-onset or worsening Renal impairment: which including cases like acute renal
failure and fanconi syndrome has reported with Tenofovir DF. While using
Tenofovir has no safety and efficacy data in patients. Routine monitoring of
calculated creatinine clearanceand serum phosphorus should be performed.
Patients with HIV-1 and HBV Co-infection: post therapy exacerbations of hepatitis may
occur In patients infected with both HIV-1 and HBV when changing of treatment
Lamivudine containing HIV-1 regimen to Lamivudine containing regimens .
PREGNANCY AND LACTATION
Pregnancy
category of lamivudine: C
Pregnancy
category of Tenofovir and Dolutegravir : B
The
drug Viropil is highly
passes via placenta, no birth defects has observed at first trimester
Ths
drug must be used with probably benefits justifies the probably risk.
Breast
feeding should not be allowed.
STORAGE AND HANDLING
Store
at temperature below 30oC
Protect
the drug from heat, moisture & light
MISSED DOSE
If
missed occurs, while you remember take it soon otherwise leave the missed
dose Maintain the regular dosing schedule
Avoid
the missed dose if possible. Please consult the doctor.
Do
not self medicate the Viropil tablets.
OVER DOSAGE
The drug overdosage has no specific antidote. If occurs
with patients then they should be monitored and provide standard supportive
treatment but Tenofovir higher dose removed by hemodialysis wih an extraction co
efficient of approx 54%
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