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 What
is Truvada
•
Truvada is an anti-HIV medication. It is in
a category of HIV medicines called nucleoside
reverse transcriptase inhibitors (NRTIs).
Truvada prevents HIV from altering the genetic
material of healthy T-cells. This prevents the
cells from producing new virus and decreases
the amount of virus in the body.
• Truvada
is marketed by Gilead Sciences. It was approved
by the U.S. Food and Drug Administration (FDA)
for use by people living with HIV in August
2004.
• Truvada
is a combination of two drugs: 300mg of Viread
(tenofovir DF) and 200mg of Emtriva
(FTC). Truvada should be prescribed by a healthcare
provider for patients who need both of these
drugs. Both of these drugs can still be purchased
individually for use in combination with other
anti-HIV drugs.
• Truvada
must be combined with at least one other anti-HIV
drug, usually a protease inhibitor (PI)
or a non-nucleoside reverse transcriptase inhibitor
(NNRTI).
• Atripla,
a combination tablet containing the NNRTI Sustiva
(efavirenz) and the tenofovir and emtricitabine
in Truvada, was approved for use in the United
States in July 2006. Truvada can still be purchased
for use in combination with anti-HIV drugs other
than Sustiva.
• Both the
Viread and the Emtriva in Truvada are active
against the hepatitis
B virus (HBV), the virus responsible for
causing hepatitis B. Although it has not been
approved by the FDA for the treatment of hepatitis
B, some doctors may prescribe Truvada to treat
both hepatitis B and HIV.
What
is known about Truvada?
•
Truvada is a tablet taken
once a day. It can be taken with or without
food.
•
Truvada should not be
any more or less effective than Viread and Emtriva
taken as separate pills together. However, it
is considered to be a much more convenient way
of taking these two anti-HIV drugs.
•
For HIV-positive adults
beginning anti-HIV drug therapy for the first
time, Truvada is listed as a "preferred"
NRTI option—used in combination with the
NNRTI Sustiva (efavirenz)—and as an "alternative"
NRTI option when combined with Viramune (nevirapine)
or a protease inhibitor.
Dosing
Dosage
Form: Film-coated tablets containing
200 mg emtricitabine and 300 mg tenofovir disoproxil
fumarate (equivalent to 245 mg of tenofovir
disoproxil).
The recommended dose of Truvada for adults 18 years
or older is one tablet once a day. Patients
with lowered creatinine clearance (30 to 49
ml/min) should receive one tablet every 48 hours.
Truvada should not be prescribed for patients
requiring dosage adjustment, such as those with
reduced renal function (creatinine clearance
less than 30 ml/min or requiring hemodialysis).
Storage: Store tablets at 25 C
(77 F); excursions permitted to 15 C to 30 C
(59 F to 86 F). Keep container tightly closed.
Pharmacology
Administration of Truvada following a high fat meal or a light
meal delayed the time of tenofovir peak plasma
concentrations (Cmax) by approximately 0.75
hour. The mean increases in tenofovir area under
the concentration-time curve (AUC) and Cmax
were approximately 35% and 15%, respectively,
when administered with a high fat or light meal,
compared to administration in the fasted state.
In previous safety and efficacy studies, tenofovir disoproxil
fumarate was taken under fed conditions. Emtricitabine
AUC and Cmax were unaffected when Truvada was
administered with either a high fat or a light
meal.
Emtricitabine is rapidly and extensively
absorbed following oral administration, reaching
Cmax at 1 to 2 hours post-dose. In one clinical
trial, the mean absolute bioavailability of
emtricitabine was 93% following multiple doses
of the drug. The mean steady state Cmax was
1.8 mcg/ml and the AUC over a 24-hour dosing
interval was 10.0 hr-mcg/ml. The mean steady
state plasma trough concentration 24 hours after
an oral dose was 0.09 mcg/ml.
Emtricitabine is less than 4% bound to
plasma proteins, and protein binding is independent
of drug concentration over a range of 0.02 to
200 mcg/ml. In vitro studies indicate that emtricitabine
does not inhibit CYP450 enzymes. Following administration
of 14C-emtricitabine, the drug was 86% recovered
in urine and 14% in feces. Thirteen percent
of urine-recovered drug were metabolites.
The plasma half-life of emtricitabine is approximately 10 hours.
Renal clearance of the drug exceeds estimated
creatinine clearance, indicating elimination
by glomerular filtration and tubular secretion.
In patients with renal impairment, Cmax and
AUC were increased.
Oral
bioavailability of tenofovir in fasted patients
is approximately 25%. Administration of tenofovir
with a high fat meal increases the oral bioavailability,
with an increase in tenofovir AUC of approximately
40% and an increase in Cmax of approximately
14%.
Food delays the time to tenofovir Cmax by approximately 1 hour.
Following oral administration of a single 300
mg dose of tenofovir to HIV infected patients
in the fasted state, Cmax is achieved in approximately
1.0 hour. Cmax and AUC values are approximately
0.296 mcg/ml and approximately 2.287 hr-mcg/ml,
respectively.
The pharmacokinetics of tenofovir are dose proportional over
a wide dose range and are not affected by repeated
dosing.
Emtricitabine and tenofovir disoproxil fumarate each inhibit
viral reverse transcriptase (RT), an enzyme
HIV requires in order to replicate, by incorporating
into viral DNA and terminating the viral DNA
chain. (For more information, see the individual
drug records for emtricitabine and tenofovir
disoproxil fumarate.)
In vitro studies indicate that neither tenofovir
disoproxil fumarate nor tenofovir are substrates
of CYP450 enzymes.
Following IV administration of tenofovir, approximately 70%
to 80% of the dose is recovered in the urine
as unchanged drug within 72 hours of dosing.
After multiple oral doses of tenofovir disoproxil
fumarate under fed conditions, approximately
32% of the administered dose is recovered in
urine over 24 hours.
Tenofovir is eliminated by a combination of glomerular filtration
and active tubular secretion. There may be competition
for elimination with other compounds that are
also renally eliminated. Tenofovir is principally
eliminated by the kidney.
Dosing adjustment is recommended in all patients with creatinine
clearance less than 50 ml/min. Dosage adjustments
for renal impairment are available in the prescribing
information. However, no safety data are available
in patients with renal dysfunction who received
tenofovir using these guidelines.
One emtricitabine/tenofovir disoproxil
fumarate tablet is bioequivalent to one emtricitabine
tablet (200 mg) plus one tenofovir disoproxil
fumarate tablet (300 mg) following single-dose
administration to healthy adults.
Adverse
Events / Toxicity
Severe acute exacerbations of hepatitis B have been reported
in patients who have discontinued emtricitabine
or tenofovir disoproxil fumarate. Hepatic function
should be monitored closely with both clinical
and laboratory follow-up for at least several
months in patients who discontinue Truvada and
are coinfected with hepatitis B virus (HBV)
and HIV. If appropriate, initiation of anti-hepatitis
B therapy may be warranted.
Emtricitabine and tenofovir disoproxil
fumarate are principally eliminated in the kidney;
therefore, dosing interval adjustments of Truvada
are recommended for patients with decreased
creatinine clearance. Truvada should not
be administered to patients with low creatinine
clearance or those who require hemodialysis.
The manufacturer (Gilead Sciences of Foster City, CA) recommends that Truvada
not be used as a component of a triple nucleoside
regimen. Use of Truvada should be avoided in
patients who are concurrently using or have
recently used a nephrotoxic agent. Patients
at risk for, or with a history of, renal dysfunction
and patients receiving concomitant nephrotoxic
agents should be monitored for changes in serum
creatinine and phosphorus.
Truvada is contraindicated in patients with previously demonstrated
hypersensitivity to any of the components of
the product, including emtricitabine and tenofovir
disoproxil fumarate.
Lactic acidosis and severe hepatomegaly
with steatosis, including fatal cases, have
been reported with the use of nucleoside analogs
alone or in combination with other antiretrovirals.
Truvada is not indicated for the treatment of
chronic HBV infection, and the safety and efficacy
of Truvada have not been established in patients
coinfected with HBV and HIV.
The
Viread in Truvada
may cause bone problems. In one clinical trial
conducted by the manufacturer involving HIV-positive
patients who were new to anti-HIV therapy, Viread
[combined with Sustiva® and Epivir®] was more
likely to cause decreased bone mineral density
(osteopenia) – which can lead to osteoporosis
– than Zerit® (d4T) [combined with Sustiva and
Epivir]. This can increase the risk of bone
breakage, including the hip, spine, and wrist.
Researchers are currently looking into the seriousness
of this possible side effect.
If
you have a history of bone fracture or are at
risk for osteopenia, your doctor may want to
consider ordering bone scans on a regular basis
while you are taking Truvada. While it's not
clear if calcium and vitamin D supplementation
can help reverse this side effect, it might
be a good idea if you have either osteopenia
or osteoporosis and are taking Viread.
Anti-HIV
drug regimens containing nucleoside reverse
transcriptase inhibitors (NRTIs), including
Truvada, can cause increased fat levels (cholesterol
and triglycerides) in the blood, abnormal body-shape
changes (lipodystrophy; including increased
fat around the abdomen, breasts, and back of
the neck, as well as decreased fat in the face,
arms, and legs), and diabetes.
If
you have hepatitis B and HIV and plan to stop
taking Truvada, your doctor might want to frequently
check your liver enzymes after stopping treatment.
This is because the Viread and Emtriva in Truvada
are also active against the hepatitis B virus
(HBV). If Truvada is stopped abruptly, it can
cause liver disease to "flare" and
damage the liver.
What
about drug interactions?
Truvada
should not be taken at the same time as Epivir
or other combination tablets that contain Epivir
(for example, Epzicom,
Combivir, or Trizivir).
This is because Epivir is very similar to the
Emtriva in Truvada,
and it is not believed that combining these
two anti-HIV drugs will make a regimen any more
effective against the virus.
Truvada should not be used in combination with
Videx/Videx EC (ddI).
HIV-positive people should also be careful if
they use Truvada in combination with Reyataz
(atazanavir), a protease inhibitor used
to treat HIV. The Viread in Truvada can decrease
Reyataz levels in the bloodstream and Reyataz
can increase Viread levels in the bloodstream.
Thus, if you are using Reyataz in combination
with Truvada, your doctor should also prescribe
low doses of Norvir
(ritonavir), another protease inhibitor
that can significantly boost the amount of Reyataz
in the bloodstream. The correct dose is 300mg
Reyataz plus 100mg Norvir, combined with the
standard daily dose of Truvada. To make sure
that the increased Viread levels do not cause
kidney damage (a possible side effect of Viread),
blood tests to monitor kidney function should
be performed regularly.
Levels of lopinavir, one of the two protease
inhibitors in Kaletra
(lopinavir/ritonavir), can decrease when
the drug is combined with Truvada. Kaletra can
also increase Viread levels—one of the
drugs in Truvada—in the bloodstream. If
Kaletra and Truvada are used together, it is
important to watch out for potential side effects
of Viread (e.g., kidney problems).
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