WARNING: POST
TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B
Discontinuation
of anti-hepatitis B therapy, including Vemlidy, may result in severe acute
exacerbations of hepatitis B. Hepatic function should be monitored closely with
both clinical and laboratory follow-up for at least several months in patients
who discontinue anti-hepatitis B therapy, including Vemlidy. If appropriate,
resumption of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)] .
Indications and
Usage for Vemlidy
Vemlidy is
indicated for the treatment of chronic hepatitis B virus (HBV) infection in
adults with compensated liver disease [see Clinical Studies
(14)] .
Vemlidy Dosage
and Administration
Testing Prior to
Initiation of Vemlidy
Prior to
initiation of Vemlidy, patients should be tested for HIV-1 infection. Vemlidy
alone should not be used in patients with HIV infection [see Warnings and
Precautions (5.2)] .
It is
recommended that serum creatinine, serum phosphorous, estimated creatinine
clearance, urine glucose, and urine protein be assessed before initiating
Vemlidy and during therapy in all patients as clinically appropriate [see Warnings and
Precautions (5.3)].
Recommended
Dosage in Adults
The recommended
dosage of Vemlidy is 25 mg (one tablet) taken orally once daily with food [see Clinical
Pharmacology (12.3)].
Dosage in
Patients with Renal Impairment
No dosage
adjustment of Vemlidy is required in patients with mild, moderate, or severe
renal impairment. Vemlidy is not recommended in patients with end stage renal
disease (estimated creatinine clearance below 15 mL per minute) [see Use in Specific
Populations (8.6) and Clinical
Pharmacology (12.3)] .
Dosage in
Patients with Hepatic Impairment
No dosage
adjustment of Vemlidy is required in patients with mild hepatic impairment
(Child-Pugh A). Vemlidy is not recommended in patients with decompensated
(Child-Pugh B or C) hepatic impairment [see Use in Specific
Populations (8.7) and Clinical
Pharmacology (12.3)].
Dosage Forms and
Strengths
Tablets: 25 mg
of tenofovir alafenamide (equivalent to 28 mg of tenofovir alafenamide
fumarate) — yellow, round, film-coated tablets, debossed with "GSI"
on one side of the tablet and "25" on the other side.
Contraindications
None.
Warnings and
Precautions
Severe Acute
Exacerbation of Hepatitis B after Discontinuation of Treatment
Discontinuation
of anti-hepatitis B therapy, including Vemlidy, may result in severe acute
exacerbations of hepatitis B. Patients who discontinue Vemlidy should be
closely monitored with both clinical and laboratory follow-up for at least
several months after stopping treatment. If appropriate, resumption of
anti-hepatitis B therapy may be warranted.
Risk of
Development of HIV-1 Resistance in Patients Coinfected with HBV and HIV-1
Due to the risk
of development of HIV-1 resistance, Vemlidy alone is not recommended for the
treatment of HIV-1 infection. The safety and efficacy of Vemlidy have not been
established in patients coinfected with HBV and HIV-1. HIV antibody testing
should be offered to all HBV-infected patients before initiating therapy with
Vemlidy, and, if positive, an appropriate antiretroviral combination regimen
that is recommended for patients coinfected with HIV-1 should be used.
New Onset or
Worsening Renal Impairment
Renal
impairment, including cases of acute renal failure and Fanconi syndrome (renal
tubular injury with severe hypophosphatemia), has been reported with the use of
tenofovir prodrugs in both animal toxicology studies and human trials. In
clinical trials of Vemlidy, there have been no cases of Fanconi syndrome or
Proximal Renal Tubulopathy (PRT).
Patients taking
tenofovir prodrugs who have impaired renal function and those taking
nephrotoxic agents, including non-steroidal anti-inflammatory drugs, are at
increased risk of developing renal-related adverse reactions [see Drug
Interactions (7.2)] .
It is
recommended that serum creatinine, serum phosphorous, estimated creatinine
clearance, urine glucose, and urine protein be assessed before initiating
Vemlidy and during therapy in all patients as clinically appropriate.
Discontinue Vemlidy in patients who develop clinically significant decreases in
renal function or evidence of Fanconi syndrome.
Lactic
Acidosis/Severe Hepatomegaly with Steatosis
Lactic acidosis
and severe hepatomegaly with steatosis, including fatal cases, have been
reported with the use of nucleoside analogs, including tenofovir DF, another
prodrug of tenofovir, alone or in combination with other antiretrovirals.
Treatment with Vemlidy 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).
Adverse
Reactions
The following
adverse reactions are discussed in other sections of the labeling:
Severe
Acute Exacerbation of Hepatitis B [see Boxed
Warning and Warnings
and Precautions (5.1)]New
Onset or Worsening of Renal Impairment [see Warnings
and Precautions (5.3)]Lactic
Acidosis/Severe Hepatomegaly with Steatosis [see Warnings
and Precautions (5.4)]
Clinical Trials
Experience
Because clinical
trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates
in the clinical trials of another drug and may not reflect the rates observed
in practice.
Adverse
Reactions in Adult Subjects with Chronic Hepatitis B and Compensated Liver
Disease
The safety
assessment of Vemlidy was based on pooled data through the Week 48 data
analysis from 1298 subjects in two randomized, double-blind, active-controlled
trials, Study 108 and Study 110, in adult subjects with chronic hepatitis B and
compensated liver disease. A total of 866 subjects received Vemlidy 25 mg once
daily [see Clinical Studies (14.1)] .
The proportion
of subjects who discontinued treatment with Vemlidy or tenofovir disoproxil
fumarate due to adverse reactions of any severity was 1.0% and 1.2%,
respectively. Table 1 displays the frequency of the adverse reaction (all
Grades) greater than or equal to 5% in the Vemlidy group.
Table 1 Adverse Reactions * (All Grades) Reported in ≥5% of Subjects with Chronic HBV
Infection and Compensated Liver Disease in Studies 108 and 110 (Week 48
analysis)
|
|
|
Vemlidy
(N=866)
|
Tenofovir Disoproxil Fumarate
(N=432)
|
|
*
Frequencies of
adverse reactions are based on all treatment-emergent adverse events,
regardless of relationship to study drug.
|
|
Headache
|
9%
|
8%
|
|
Abdominal pain
|
7%
|
6%
|
|
Fatigue
|
6%
|
5%
|
|
Cough
|
6%
|
6%
|
|
Nausea
|
5%
|
5%
|
|
Back pain
|
5%
|
4%
|
Renal Laboratory
Tests
In a pooled
analysis of Studies 108 and 110 in adult subjects with chronic hepatitis B and
a median baseline eGFR of 106 and 105 mL per minute (for the Vemlidy and
tenofovir disoproxil fumarate [TDF] groups, respectively), mean serum
creatinine increased by less than 0.1 mg/dL and median serum phosphorus
decreased by 0.1 mg/ dL in both treatment groups. Median change from baseline
in eGFR was -1.2 mL per minute in the Vemlidy group and -5.4 mL per minute in
those receiving TDF. The long-term clinical significance of these renal
laboratory changes on adverse reaction frequencies between Vemlidy and TDF is
not known.
Decrease in Bone
Mineral Density
In a pooled
analysis of Studies 108 and 110, the mean percentage change in bone mineral
density (BMD) from baseline to Week 48 as assessed by dual-energy X-ray
absorptiometry (DXA) was -0.6% with Vemlidy compared to -2.4% with TDF at the
lumbar spine and -0.2% compared to -1.9% at the total hip. BMD declines of 5%
or greater at the lumbar spine were experienced by 6% of Vemlidy subjects and
20% of TDF subjects. BMD declines of 7% or greater at the femoral neck were
experienced by 3% of Vemlidy subjects and 6% of TDF subjects. The long-term
clinical significance of these BMD changes is not known.
Laboratory
Abnormalities
The frequency of
laboratory abnormalities (Grades 3–4) occurring in at least 2% of subjects
receiving Vemlidy in Studies 108 and 110 are presented in Table 2.
Table 2 Laboratory Abnormalities (Grades 3–4) Reported
in ≥2% of Subjects with Chronic HBV Infection and Compensated Liver Disease
in Studies 108 and 110 (Week 48 analysis)
|
|
Laboratory Parameter Abnormality *
|
Vemlidy
(N=866)
|
Tenofovir Disoproxil Fumarate
(N=432)
|
|
*
Frequencies are
based on treatment-emergent laboratory abnormalities.
|
|
ALT (>5 × ULN)
|
8%
|
9%
|
|
Glycosuria (≥3+)
|
5%
|
1%
|
|
LDL-cholesterol (fasted) (>190 mg/dL)
|
4%
|
<1%
|
|
AST (>5 × ULN)
|
3%
|
5%
|
|
Creatine Kinase (≥10 × ULN)
|
3%
|
3%
|
|
Serum Amylase (>2.0 × ULN)
|
3%
|
2%
|
Amylase and
Lipase Elevations and Pancreatitis
In Studies 108
and 110, seven subjects treated with Vemlidy with elevated amylase levels had
associated symptoms, such as nausea, low back pain, abdominal tenderness,
biliary pancreatitis and pancreatitis. Of these seven, two subjects
discontinued Vemlidy due to elevated amylase and/or lipase; one subject experienced
recurrence of adverse events when Vemlidy was restarted. No subject treated
with tenofovir disoproxil fumarate had associated symptoms or discontinued
treatment.
Serum Lipids
Changes from
baseline in total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides,
and total cholesterol to HDL ratio among subjects treated with Vemlidy and
tenofovir disoproxil fumarate are presented in Table 3.
Table 3 Lipid Abnormalities: Mean Change from Baseline
in Lipid Parameters in Patients with Chronic HBV Infection and Compensated
Liver Disease in Studies 108 and 110 (Week 48 Analysis)
|
|
|
Vemlidy
(N=866)
|
Tenofovir Disoproxil Fumarate
(N=432)
|
|
|
Baseline
|
Week 48
|
Baseline
|
Week 48
|
|
|
mg/dL
|
Change *
|
mg/dL
|
Change *
|
|
*
The change from
baseline is the mean of within-subject changes from baseline for subjects
with both baseline and Week 48 values.
|
|
Total Cholesterol (fasted)
|
188 [n=835]
|
0 [n=772]
|
193 [n=423]
|
-25 [n=394]
|
|
HDL-Cholesterol (fasted)
|
60 [n=835]
|
-4 [n=771]
|
61 [n=423]
|
-10 [n=394]
|
|
LDL-Cholesterol (fasted)
|
116 [n=835]
|
+6 [n=772]
|
120 [n=423]
|
-11 [n=394]
|
|
Triglycerides (fasted)
|
102 [n=836]
|
+11 [n=773]
|
102 [n=423]
|
-10 [n=394]
|
|
Total Cholesterol to HDL ratio
|
3 [n=835]
|
0 [n=771]
|
3 [n=423]
|
0 [n=394]
|
Drug
Interactions
Potential for
Other Drugs to Affect Vemlidy
Vemlidy is a
substrate of P-glycoprotein (P-gp) and BCRP. Drugs that strongly affect P-gp
and BCRP activity may lead to changes in tenofovir alafenamide absorption
(see Table 4). Drugs that
induce P-gp activity are expected to decrease the absorption of tenofovir
alafenamide, resulting in decreased plasma concentrations of tenofovir
alafenamide, which may lead to loss of therapeutic effect of Vemlidy.
Coadministration of Vemlidy with other drugs that inhibit P-gp and BCRP may
increase the absorption and plasma concentration of tenofovir alafenamide.
Drugs Affecting
Renal Function
Because
tenofovir is primarily excreted by the kidneys by a combination of glomerular
filtration and active tubular secretion, coadministration of Vemlidy with drugs
that reduce renal function or compete for active tubular secretion may increase
concentrations of tenofovir and other renally eliminated drugs and this may
increase the risk of adverse reactions. Some examples of drugs that are
eliminated by active tubular secretion include, but are not limited to,
acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir,
aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and
Precautions (5.3)] .
Established and
Other Potentially Significant Interactions
Table 4 provides
a listing of established or potentially clinically significant drug
interactions. The drug interactions described are based on studies conducted
with tenofovir alafenamide or are predicted drug interactions that may occur
with Vemlidy. [For magnitude of interaction, see Clinical
Pharmacology (12.3)] . Information regarding potential
drug-drug interactions with HIV antiretrovirals is not provided (see the
prescribing information for emtricitabine/tenofovir alafenamide for
interactions with HIV antiretrovirals). The table includes potentially
significant interactions but is not all inclusive.
Table 4 Established and Other Potentially Significant
Drug Interactions *
|
|
Concomitant Drug Class: Drug
Name
|
Effect on Concentration †
|
Clinical Comment
|
|
*
This table is not all inclusive.
†
↓ = decrease.
‡
Indicates that a drug interaction study was conducted.
§
P-gp inducer
|
|
Anticonvulsants:
carbamazepine ‡§
oxcarbazepine §
phenobarbital §
phenytoin §
|
↓ tenofovir alafenamide
|
When coadministered with carbamazepine, the tenofovir
alafenamide dose should be increased to two tablets once daily.
Coadministration of Vemlidy with oxcarbazepine, phenobarbital, or phenytoin
is not recommended.
|
|
Antimycobacterial:
Rifabutin §
Rifampin §
Rifapentine §
|
↓ tenofovir alafenamide
|
Coadministration of Vemlidy with rifabutin, rifampin or
rifapentine is not recommended.
|
|
Herbal Products:
St. John's wort §(Hypericum perforatum)
|
↓ tenofovir alafenamide
|
Coadministration of Vemlidy with St. John's wort is not
recommended.
|
Drugs without
Clinically Significant Interactions with Vemlidy
Based on drug
interaction studies conducted with Vemlidy, no clinically significant drug
interactions have been observed with: ethinyl estradiol, itraconazole,
ketoconazole, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, and
sofosbuvir.
USE IN SPECIFIC
POPULATIONS
Pregnancy
Pregnancy
Exposure Registry
There is a
pregnancy exposure registry that monitors pregnancy outcomes in women exposed
to Vemlidy during pregnancy. Healthcare providers are encouraged to register
patients by calling the Antiretroviral Pregnancy Registry (APR) at
1-800-258-4263.
Risk Summary
There are no
human data on the use of Vemlidy in pregnant women to inform a drug-associated
risks of adverse fetal developmental outcome. In animal studies, no adverse
developmental effects were observed when tenofovir alafenamide was administered
during the period of organogenesis at exposure equal to or 51 times (rats and
rabbits, respectively) the tenofovir alafenamide exposure at the recommended
daily dose of Vemlidy [see Data]. No adverse
effects were observed in the offspring when TDF (tenofovir disoproxil fumarate)
was administered through lactation at tenofovir exposures of approximately 12
times the exposure at the recommended daily dosage of Vemlidy.
The background
risk of major birth defects and miscarriage for the indicated population is
unknown. In the U.S. general population, the estimated background risk of major
birth defects and miscarriage in clinically recognized pregnancies is 2–4% and
15–20%, respectively.
Data
Animal Data
Embryonic fetal
development studies performed in rats and rabbits revealed no evidence of
impaired fertility or harm to the fetus. The embryo-fetal NOAELs (no observed
adverse effect level) in rats and rabbits occurred at tenofovir alafenamide
exposures similar to and 51 times higher than, respectively, the exposure in
humans at the recommended daily dose. Tenofovir alafenamide is rapidly
converted to tenofovir; the observed tenofovir exposure in rats and rabbits
were 54 (rats) and 85 (rabbits) times higher than human tenofovir exposures at
the recommended daily dose.
Tenofovir
alafenamide was administered orally to pregnant rats (25, 100, or 250
mg/kg/day) and rabbits (10, 30, or 100 mg/kg/day) through organogenesis (on
gestation days 6 through 17, and 7 through 20, respectively). No adverse
embryo-fetal effects were observed in rats and rabbits at tenofovir alafenamide
exposures approximately similar to (rats) and 51 (rabbits) times higher than
the exposure in humans at the recommended daily dose of Vemlidy. Tenofovir
alafenamide is rapidly converted to tenofovir; the observed tenofovir exposures
in rats and rabbits were 54 (rats) and 85 (rabbits) times higher than human
tenofovir exposures at the recommended daily dose. Since tenofovir alafenamide
is rapidly converted to tenofovir and a lower tenofovir exposure in rats and
mice was observed after tenofovir alafenamide administration compared to TDF,
another prodrug for tenofovir administration, a pre/postnatal development study
in rats was conducted only with TDF. Doses up to 600 mg/kg/day were
administered through lactation; no adverse effects were observed in the
offspring on gestation day 7 [and lactation day 20] at tenofovir exposures of
approximately 12 [18] times higher than the exposures in humans at the
recommended daily dose of Vemlidy.
Lactation
Risk Summary
It is not known
whether Vemlidy and its metabolites are present in human breast milk, affect
human milk production, or have effects on the breastfed infant. Tenofovir has
been shown to be present in the milk of lactating rats and rhesus monkeys after
administration of TDF [see Data] . It is
not known if tenofovir alafenamide can be present in animal milk. The
developmental and health benefits of breastfeeding should be considered along
with the mother's clinical need for Vemlidy and any potential adverse effects
on the breastfed infant from Vemlidy or from the underlying maternal condition.
Data
Animal Data
Studies in rats
and monkeys have demonstrated that tenofovir is secreted in milk. Tenofovir was
excreted into the milk of lactating rats following oral administration of TDF
(up to 600 mg/kg/day) at up to approximately 24% of the median plasma
concentration in the highest dosed animals at lactation day 11 [see Data (8.1)]. Tenofovir
was excreted into the milk of lactating monkeys following a single subcutaneous
(30 mg/kg) dose of tenofovir at concentrations up to approximately 4% of plasma
concentration, resulting in exposure (AUC) of approximately 20% of plasma
exposure.
Pediatric Use
Safety and
effectiveness of Vemlidy in pediatric patients less than 18 years of age have
not been established.
Geriatric Use
Clinical trials
of Vemlidy did not include sufficient numbers of subjects aged 65 and over to
determine whether they respond differently from younger subjects.
Renal Impairment
No dosage
adjustment of Vemlidy is required in patients with mild, moderate, or severe
renal impairment. Vemlidy is not recommended in patients with end stage renal
disease (estimated creatinine clearance below 15 mL per minute) [see Clinical
Pharmacology (12.3)] .
Hepatic
Impairment
No dosage adjustment
of Vemlidy is required in patients with mild hepatic impairment (Child-Pugh A).
The safety and efficacy of Vemlidy in patients with decompensated cirrhosis
(Child-Pugh B or C) have not been established; therefore Vemlidy is not
recommended in patients with decompensated (Child-Pugh B or C) hepatic
impairment [see Dosage and Administration (2.4) and Clinical
Pharmacology (12.3)].
Overdosage
If overdose
occurs, monitor patient for evidence of toxicity. Treatment of overdosage with
Vemlidy consists of general supportive measures including monitoring of vital
signs as well as observation of the clinical status of the patient. Tenofovir
is efficiently removed by hemodialysis with an extraction coefficient of
approximately 54%.
Vemlidy
Description
Vemlidy is a
tablet containing tenofovir alafenamide for oral administration. Tenofovir
alafenamide, a hepatitis B virus (HBV) nucleoside analog reverse transcriptase
inhibitor, is converted in vivo to tenofovir, an acyclic
nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.
Each tablet
contains 25 mg of tenofovir alafenamide (equivalent to 28 mg of tenofovir
alafenamide fumarate). The tablets include the following inactive ingredients:
croscarmellose sodium, lactose monohydrate, magnesium stearate, and
microcrystalline cellulose. The tablets are film coated with a coating material
containing: iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc,
and titanium dioxide.
The chemical
name of tenofovir alafenamide fumarate drug substance is L-alanine, N-[( S)-[[(1 R)-2-(6-amino-9 H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-,
1-methylethyl ester, (2 E)-2-butenedioate (2:1).
It has an
empirical formula of C 21H 29O 5N 6P∙½(C 4H 4O 4) and a formula
weight of 534.50. It has the following structural formula:
Tenofovir
alafenamide fumarate is a white to off-white or tan powder with a solubility of
4.7 mg per mL in water at 20 °C.
Vemlidy -
Clinical Pharmacology
Mechanism of
Action
Tenofovir
alafenamide is an antiviral drug against the hepatitis B virus [see Microbiology
(12.4)] .
Pharmacodynamics
Cardiac
Electrophysiology
In a thorough
QT/QTc study in 48 healthy subjects, tenofovir alafenamide at the recommended
dose or at a dose 5 times the recommended dose did not affect the QT/QTc
interval and did not prolong the PR interval.
Pharmacokinetics
The
pharmacokinetic properties of Vemlidy are provided in Table 5. The multiple
dose PK parameters of tenofovir alafenamide and its metabolite tenofovir are
provided in Table 6.
Table 5 Pharmacokinetic Properties of Vemlidy
|
|
|
Tenofovir Alafenamide
|
|
CES1 = carboxylesterase 1; PBMCs = peripheral blood
mononuclear cells.
|
|
*
Values refer to geometric mean ratio in AUC last
[fed/fasted] and (90% confidence interval). High fat meal = ~800 kcal, 50%
fat.
†
In vivo, TAF is hydrolyzed within cells to form
tenofovir (major metabolite), which is phosphorylated to the active
metabolite, tenofovir diphosphate. In vitro studies have shown that TAF is
metabolized to tenofovir by CES1 in hepatocytes, and by cathepsin A in PBMCs
and macrophages.
‡
t 1/2 values refer to median terminal plasma half-life.
§
Dosing in mass
balance study: TAF 25 mg (single dose administration of [ 14C] TAF).
|
|
Absorption
|
|
T max (h)
|
0.48
|
|
Effect of high fat meal (relative to fasting):
AUC last Ratio *
|
1.65 (1.51, 1.81)
|
|
Distribution
|
|
% Bound to human plasma proteins
|
80%
|
|
Source of protein binding data
|
Ex vivo
|
|
Blood-to-plasma ratio
|
1.0
|
|
Metabolism
|
|
Metabolism †
|
CES1 (hepatocytes)
Cathepsin A (PBMCs)
CYP3A (minimal)
|
|
Elimination
|
|
Major route of elimination
|
Metabolism (>80% of oral dose)
|
|
t 1/2 (h) ‡
|
0.51
|
|
% Of dose excreted in urine §
|
<1
|
|
% Of dose excreted in feces §
|
31.7
|
Table 6 Multiple Dose PK Parameters of Tenofovir
Alafenamide and its Metabolite Tenofovir Following Oral Administration in
Adults with Chronic Hepatitis B
|
|
Parameter
Mean (CV%)
|
Tenofovir Alafenamide *
|
Tenofovir *
|
|
CV = coefficient of variation; NA = not applicable
|
|
*
From Intensive
PK analyses in Study 108 and Study 110; N = 8.
|
|
C max
(microgram per mL)
|
0.27 (63.3)
|
0.03 (24.6)
|
|
AUC tau
(microgram∙hour per mL)
|
0.27 (47.8)
|
0.40 (35.2)
|
|
C trough (microgram per mL)
|
NA
|
0.01 (39.6)
|
|
|
|
|
|
Specific
Populations
Geriatric
Patients, Race, and Gender
No clinically
relevant differences in tenofovir alafenamide or tenofovir pharmacokinetics due
to race or gender have been identified. Limited data in subjects aged 65 and
over suggest a lack of clinically relevant differences in tenofovir alafenamide
or tenofovir pharmacokinetics [see Use in Specific Populations (8.5)] .
Patients with
Renal Impairment
Relative to
subjects with normal renal function (estimated creatinine clearance ≥90
mL/min), the tenofovir alafenamide and tenofovir systemic exposures in subjects
with severe renal impairment were 1.9-fold and 5.7-fold higher, respectively.
The pharmacokinetics of tenofovir alafenamide have not been evaluated in
patients with creatinine clearance less than 15 mL per minute.
Patients with
Hepatic Impairment
Relative to
subjects with normal hepatic function, tenofovir alafenamide and tenofovir
systemic exposures were 7.5% and 11% lower in subjects with mild hepatic
impairment, respectively.
HIV and/or
Hepatitis C Virus Coinfection
The pharmacokinetics
of tenofovir alafenamide have not been fully evaluated in subjects coinfected
with HIV and/or hepatitis C virus.
Drug Interaction
Studies
[see Drug
Interactions (7)]
The effects of coadministered
drugs on the exposure of tenofovir alafenamide are shown in Table 7. The
effects of tenofovir alafenamide on the exposure of coadministered drugs are
shown in Table 8 [For information regarding clinical
recommendations, see Drug Interactions (7)]. Information
regarding potential drug-drug interactions with HIV antiretrovirals is not
provided (see the prescribing information for emtricitabine/tenofovir
alafenamide for interactions with HIV antiretrovirals).
Table 7 Drug Interactions: Changes in Pharmacokinetic
Parameters for Tenofovir Alafenamide in the Presence of the Coadministered
Drug *
|
|
|
Coadministered Drug
|
Dose of Coadministered Drug
(mg)
|
Tenofovir Alafenamide (mg)
|
N
|
Geometric Mean Ratio of TAF
Pharmacokinetic Parameters (90% CI) †;
No effect = 1.00
|
|
|
C max
|
AUC
|
C min
|
|
|
NC = not calculated
|
|
|
*
All interaction studies conducted in healthy subjects.
†
All no effect boundaries are 70%–143%.
‡
Study conducted with emtricitabine/tenofovir
alafenamide.
§
A representative inhibitor of P-glycoprotein.
¶
Study conducted with
emtricitabine/rilpivirine/tenofovir alafenamide.
#
Study conducted
with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.
|
|
|
Carbamazepine
|
300 twice daily
|
25 once daily ‡
|
26
|
0.43
(0.36, 0.51)
|
0.45
(0.40, 0.51)
|
NC
|
|
|
Cobicistat §
|
150 once daily
|
8 once daily
|
12
|
2.83
(2.20, 3.65)
|
2.65
(2.29, 3.07)
|
NC
|
|
|
Ledipasvir/Sofosbuvir
|
90/400 once daily
|
25 once daily ¶
|
42
|
1.03
(0.94, 1.14)
|
1.32
(1.24, 1.40)
|
NC
|
|
|
Sertraline
|
50 once daily
|
10 once daily #
|
19
|
1.00
(0.86, 1.16)
|
0.96
(0.89, 1.03)
|
NC
|
|
Table 8 Drug Interactions: Changes in Pharmacokinetic
Parameters for Coadministered Drug in the Presence of Tenofovir
Alafenamide *
|
|
|
Coadministered Drug
|
Dose of Coadministered Drug
(mg)
|
Tenofovir Alafenamide (mg)
|
N
|
Geometric Mean Ratio of
Coadministered Drug Pharmacokinetic Parameters (90% CI) †;
No effect = 1.00
|
|
|
C max
|
AUC
|
C min
|
|
|
NC = not calculated
|
|
|
*
All interaction studies conducted in healthy subjects.
†
All no effect boundaries are 70%–143%.
‡
Study conducted with
emtricitabine/rilpivirine/tenofovir alafenamide.
§
The predominant circulating nucleoside metabolite of
sofosbuvir.
¶
A sensitive CYP3A4 substrate.
#
Study conducted with emtricitabine/tenofovir
alafenamide.
Þ
Study conducted
with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.
|
|
|
Ledipasvir
|
90 ledipasvir / 400 sofosbuvir once daily
|
25 once daily ‡
|
41
|
1.01
(0.97, 1.05)
|
1.02
(0.97, 1.06)
|
1.02
(0.98, 1.07)
|
|
|
Sofosbuvir
|
0.96
(0.89, 1.04)
|
1.05
(1.01, 1.09)
|
NC
|
|
|
GS-331007 §
|
1.08
(1.05, 1.11)
|
1.08
(1.06, 1.10)
|
1.10
(1.07, 1.12)
|
|
|
Midazolam ¶
|
2.5 once daily orally
|
25 once daily
|
18
|
1.02
(0.92, 1.13)
|
1.12
(1.03, 1.22)
|
NC
|
|
|
1 once daily IV
|
0.99
(0.89, 1.11)
|
1.08
(1.04, 1.14)
|
NC
|
|
|
Norgestromin
|
norgestimate 0.180/0.215/0.250 once daily / ethinyl
estradiol 0.025 once daily
|
25 once daily #
|
29
|
1.17
(1.07, 1.26)
|
1.12
(1.07, 1.17)
|
1.16
(1.08, 1.24)
|
|
|
Norgestrel
|
1.10
(1.02, 1.18)
|
1.09
(1.01, 1.18)
|
1.11
(1.03, 1.20)
|
|
|
Ethinyl estradiol
|
1.22
(1.15, 1.29)
|
1.11
(1.07, 1.16)
|
1.02
(0.93, 1.12)
|
|
|
Sertraline
|
50 single dose
|
10 once daily Þ
|
19
|
1.14
(0.94, 1.38)
|
1.09
(0.90, 1.32)
|
NC
|
|
|
|
|
|
|
|
|
|
|
|
Microbiology
Mechanism of
Action
Tenofovir
alafenamide is a phosphonamidate prodrug of tenofovir (2'-deoxyadenosine
monophosphate analog). Tenofovir alafenamide as a lipophilic cell-permeant
compound enters primary hepatocytes by passive diffusion and by the hepatic
uptake transporters OATP1B1 and OATP1B3. Tenofovir alafenamide is then
converted to tenofovir through hydrolysis primarily by carboxylesterase 1
(CES1) in primary hepatocytes. Intracellular tenofovir is subsequently
phosphorylated by cellular kinases to the pharmacologically active metabolite
tenofovir diphosphate. Tenofovir diphosphate inhibits HBV replication through
incorporation into viral DNA by the HBV reverse transcriptase, which results in
DNA chain-termination.
Tenofovir
diphosphate is a weak inhibitor of mammalian DNA polymerases that include
mitochondrial DNA polymerase γ and there is no evidence of toxicity to
mitochondria in cell culture.
Antiviral
Activity in Cell Culture
The antiviral
activity of tenofovir alafenamide was assessed in a transient transfection
assay using HepG2 cells against a panel of HBV clinical isolates representing
genotypes A-H. The EC 50 (50% effective concentration)
values for tenofovir alafenamide ranged from 34.7 to 134.4 nM, with an overall
mean EC 50 value of 86.6 nM. The CC 50 (50%
cytotoxicity concentration) values in HepG2 cells were greater than 44,400 nM.
In cell culture combination antiviral activity studies of tenofovir with the
HBV nucleoside reverse transcriptase inhibitors entecavir, lamivudine, and
telbivudine, no antagonistic activity was observed.
Resistance in
Clinical Trials
In a pooled
analysis of treatment-naïve and treatment-experienced subjects receiving
Vemlidy in Studies 108 and 110, genotypic resistance analysis was performed on
paired baseline and on-treatment HBV isolates for subjects who either
experienced virologic breakthrough (2 consecutive visits with HBV DNA greater
than or equal to 69 IU/mL [400 copies/mL] after having been less than 69 IU/mL,
or 1.0-log 10 or greater increase in HBV DNA from nadir) through
Week 48, or had HBV DNA greater than or equal to 69 IU/mL at early
discontinuation at or after Week 24. Treatment-emergent amino acid
substitutions in the HBV reverse transcriptase domain, all occurring at
polymorphic positions, were observed in some HBV isolates evaluated (5/20);
however, no specific substitutions occurred at a sufficient frequency to be
associated with resistance to Vemlidy.
Cross-Resistance
The antiviral
activity of tenofovir alafenamide was evaluated against a panel of isolates
containing substitutions associated with HBV nucleoside reverse transcriptase
inhibitor resistance in a transient transfection assay using HepG2 cells. HBV
isolates expressing the lamivudine resistance-associated substitutions
rtM204V/I (±rtL180M±rtV173L) and expressing the entecavir resistance-associated
substitutions rtT184G, rtS202G, or rtM250V in the presence of rtL180M and
rtM204V showed less than 2-fold reduced susceptibility (within the inter-assay
variability) to tenofovir alafenamide. HBV isolates expressing the rtA181T,
rtA181V, or rtN236T single substitutions associated with resistance to adefovir
also had less than 2-fold changes in EC 50 values;
however, the HBV isolate expressing the rtA181V plus rtN236T double
substitutions exhibited reduced susceptibility (3.7-fold) to tenofovir
alafenamide. The clinical relevance of these substitutions is not known.
Nonclinical
Toxicology
Carcinogenesis,
Mutagenesis, Impairment of Fertility
Since tenofovir
alafenamide is rapidly converted to tenofovir and a lower tenofovir exposure in
rats and mice was observed after tenofovir alafenamide administration compared
to tenofovir disoproxil fumarate administration, carcinogenicity studies were
conducted only with tenofovir disoproxil fumarate. Long-term oral
carcinogenicity studies of tenofovir disoproxil fumarate in mice and rats were
carried out at exposures up to approximately 10 times (mice) and 4 times (rats)
those observed in humans at the 300 mg therapeutic dose of tenofovir disoproxil
fumarate for chronic hepatitis B. The tenofovir exposure in these studies was
approximately 151 times (mice) and 50 times (rat) those observed in humans
after administration of Vemlidy treatment. At the high dose in female mice,
liver adenomas were increased at tenofovir exposures approximately 151 times
those observed after Vemlidy administration in humans. In rats, the study was
negative for carcinogenic findings.
Tenofovir
alafenamide was not genotoxic in the reverse mutation bacterial test (Ames
test), mouse lymphoma or rat micronucleus assays.
There were no
effects on fertility, mating performance or early embryonic development when
tenofovir alafenamide was administered to male rats at a dose equivalent to 155
times the human dose based on body surface area comparisons for 28 days prior
to mating and to female rats for 14 days prior to mating through Day 7 of
gestation.
Animal
Toxicology and/or Pharmacology
Minimal to
slight infiltration of mononuclear cells in the posterior uvea was observed in
dogs with similar severity after three- and nine-month administration of
tenofovir alafenamide; reversibility was seen after a three month recovery
period. At the NOAEL for eye toxicity, the systemic exposure in dogs was 5
(tenofovir alafenamide) and 14 (tenofovir) times the exposure seen in humans at
the recommended daily Vemlidy dosage.
Clinical Studies
Clinical Trials
in Adults with Chronic Hepatitis B Virus Infection and Compensated Liver
Disease
The efficacy and
safety of Vemlidy in the treatment of adults with chronic hepatitis B virus
infection with compensated liver disease are based on 48-week data from two
randomized, double-blind, active-controlled studies, Study 108 (N=425) and
Study 110 (N=873). In both studies, besides study treatment, patients were not
allowed to receive other nucleosides, nucleotides, or interferon.
In Study 108,
HBeAg-negative treatment-naïve and treatment-experienced subjects with
compensated liver disease (no evidence of ascites, hepatic encephalopathy,
variceal bleeding, INR <1.5× ULN, total bilirubin <2.5× ULN, and albumin
>3.0 mg/dL) were randomized in a 2:1 ratio to receive Vemlidy 25 mg (N=285)
once daily or tenofovir disoproxil fumarate 300 mg (N=140) once daily for 48
weeks. The mean age was 46 years, 61% were male, 72% were Asian, 25% were
White, 2% were Black, and 1% were other races. 24%, 38%, and 31% had HBV
genotype B, C, and D, respectively. 21% were treatment experienced [previous
treatment with oral antivirals, including entecavir (N=41), lamivudine (N=42),
tenofovir disoproxil fumarate (N=21), or other (N=18)]. At baseline, mean
plasma HBV DNA was 5.8 log 10 IU/mL, mean serum ALT was 94 U/L,
and 9% of subjects had a history of cirrhosis.
In Study 110,
HBeAg-positive treatment-naïve and treatment-experienced subjects with
compensated liver disease were randomized in a 2:1 ratio to receive Vemlidy 25
mg (N=581) once daily or tenofovir disoproxil fumarate 300 mg (N=292) once
daily for 48 weeks. The mean age was 38 years, 64% were male, 82% were Asian,
17% were White, and 1% were Black or other races. 17%, 52%, and 23% had HBV
genotype B, C, and D, respectively. 26% were treatment experienced [previous
treatment with oral antivirals, including adefovir (N=42), entecavir (N=117),
lamivudine (N=84), telbivudine (N=25), tenofovir disoproxil fumarate (N=70), or
other (n=17)]. At baseline, mean plasma HBV DNA was 7.6 log 10 IU/mL,
mean serum ALT was 120 U/L, and 7% of subjects had a history of cirrhosis.
In both studies,
randomization was stratified on prior treatment history (nucleoside naïve or
experienced) and baseline HBV DNA (<7, ≥7 to <8, and ≥8 log 10 IU/mL in
Study 108; and <8 and ≥8 log 10 IU/mL in Study 110). The efficacy
endpoint in both trials was the proportion of subjects with plasma HBV DNA
levels below 29 IU/mL at Week 48. Additional efficacy endpoints include the
proportion of subjects with ALT normalization, HBsAg loss and seroconversion,
and HBeAg loss and seroconversion in Study 110.
Treatment
outcomes of Studies 108 and 110 at Week 48 are presented in Table 9 and Table
10.
Table 9 Studies 108 and 110: HBV DNA Virologic Outcome
at Week 48 * in Patients with Chronic HBV Infection and Compensated Liver
Disease
|
|
|
Study 108 (HBeAg-Negative)
|
Study 110 (HBeAg-Positive)
|
|
|
Vemlidy
(N=285)
|
Tenofovir Disoproxil Fumarate
(N=140)
|
Vemlidy
(N=581)
|
Tenofovir Disoproxil Fumarate
(N=292)
|
|
*
Missing = failure analysis
†
Adjusted by baseline plasma HBV DNA categories and oral
antiviral treatment status strata.
‡
Treatment-naïve subjects received <12 weeks of oral
antiviral treatment with any nucleoside or nucleotide analog including TDF or
Vemlidy.
§
Includes
subjects who discontinued due to lack of efficacy, adverse event or death,
for reasons other than an AE, death or lack or loss of efficacy, e.g.,
withdrew consent, loss to follow-up, etc., or missing data during Week 48
window but still on study drug.
|
|
HBV DNA <29 IU/mL
|
94%
|
93%
|
64%
|
67%
|
|
Treatment Difference †
|
1.8% (95% CI = -3.6% to 7.2%)
|
-3.6% (95% CI = -9.8% to 2.6%)
|
|
HBV DNA ≥ 29 IU/mL
|
2%
|
3%
|
31%
|
30%
|
|
Baseline HBV DNA
<7 log 10 IU/mL
≥7 log 10 IU/mL
|
96% (221/230)
85% (47/55)
|
92% (107/116)
96% (23/24)
|
N/A
|
N/A
|
|
Baseline HBV DNA
<8 log 10 IU/mL
≥8 log 10 IU/mL
|
N/A
|
N/A
|
82% (254/309)
43% (117/272)
|
82% (123/150)
51% (72/142)
|
|
Nucleoside Naïve ‡
Nucleoside Experienced
|
94% (212/225)
93% (56/60)
|
93% (102/110)
93% (28/30)
|
68% (302/444)
50% (69/137)
|
70% (156/223)
57% (39/69)
|
|
No Virologic Data at Week 48 §
|
4%
|
4%
|
5%
|
3%
|
In Study 108,
the proportion of subjects with cirrhosis who achieved HBV DNA <29 IU/mL at
Week 48 was 92% (22/24) in the Vemlidy group and 93% (13/14) in the TDF group.
The corresponding proportions in Study 110 were 63% (26/41) and 67% (16/24) in
the Vemlidy and TDF groups, respectively.
Table 10 Additional Efficacy Parameters at Week
48 *
|
|
|
Study 108 (HBeAg-Negative)
|
Study 110 (HBeAg-Positive)
|
|
|
Vemlidy
(N=285)
|
Tenofovir Disoproxil Fumarate
(N=140)
|
Vemlidy
(N=581)
|
Tenofovir Disoproxil Fumarate
(N=292)
|
|
N/A = not applicable
|
|
*
Missing = failure analysis
†
The population used for analysis of ALT normalization
included only subjects with ALT above upper limit of normal (ULN) of the
central laboratory range (>43 U/L for males aged 18 to <69 years and
>35 U/L for males ≥69 years; >34 U/L for females 18 to <69 years and
>32 U/L for females ≥69 years) at baseline.
‡
The population used for analysis of ALT normalization
included only subjects with ALT above ULN of the American Association of the
Study of Liver Diseases (AASLD) criteria (>30 U/L males and >19 U/L
females) at baseline.
§
The population
used for serology analysis included only subjects with antigen (HBeAg)
positive and anti-body (HBeAb) negative or missing at baseline.
|
|
ALT
Normalized ALT (Central Lab) †
|
83%
|
75%
|
72%
|
67%
|
|
Normalized ALT (AASLD) ‡
|
50%
|
32%
|
45%
|
36%
|
|
Serology
HBeAg Loss / Seroconversion §
|
N/A
|
N/A
|
14% / 10%
|
12% / 8%
|
|
HBsAg Loss / Seroconversion
|
0 / 0
|
0 / 0
|
1% / 1%
|
<1% / 0
|
How
Supplied/Storage and Handling
Vemlidy tablets
containing 25 mg of tenofovir alafenamide are yellow, round, film-coated,
debossed with "GSI" on one side and "25" on the other side.
Each bottle contains 30 tablets (NDC 61958-2301-1), a silica gel desiccant,
polyester coil, and is closed with a child-resistant closure.
Store below 30
°C (86 °F).
Keep
container tightly closed.Dispense
only in original container.
Patient
Counseling Information
Advise the
patient to read the FDA-approved patient labeling (Patient Information).
Severe Acute
Exacerbation of Hepatitis after Discontinuation of Treatment
Inform patients
that discontinuation of anti-hepatitis B therapy, including Vemlidy, may result
in severe acute exacerbations of hepatitis B . Advise the
patient to not discontinue Vemlidy without first informing their healthcare
provider [see Warnings and Precautions (5.1)] .
Risk of
Development of HIV-1 Resistance in Patients with HIV-1 Coinfection
Inform patients
that if they have or develop HIV infection and are not receiving effective HIV
treatment, Vemlidy may increase the risk of development of resistance to HIV
medication [see Dosage and Administration (2.1) and Warnings and
Precautions (5.2)] .
New Onset or
Worsening Renal Impairment
Advise patients
that renal impairment, including cases of acute renal failure, has been
reported in association with the use of tenofovir prodrugs [see Warnings and
Precautions (5.3)].
Lactic Acidosis
and Severe Hepatomegaly
Lactic acidosis
and severe hepatomegaly with steatosis, including fatal cases, have been
reported with use of drugs similar to Vemlidy. Advise patients to contact their
healthcare provider immediately and stop Vemlidy if they develop clinical
symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and
Precautions (5.4)].
Drug
Interactions
Advise patients
to report to their healthcare provider the use of any other prescription or
non-prescription medication or herbal products including St. John's wort, as
Vemlidy may interact with other drugs [see Drug
Interactions (7)] .
Missed Dosage
Inform patients
that it is important to take Vemlidy on a regular dosing schedule with food and
to avoid missing doses, as it can result in development of resistance [see Dosage and
Administration (2.2)] .
Pregnancy
Registry
Inform patients
that there is an antiretroviral pregnancy registry to monitor fetal outcomes of
pregnant women exposed to Vemlidy [see Use in Specific
Populations (8.1)].
Manufactured and
distributed by: Gilead Sciences, Inc. Foster City, CA 94404
© 2017 Gilead
Sciences, Inc. All rights reserved.
|
This Patient Information has been approved by the U.S.
Food and Drug Administration
|
Revised: 04/2017
|
|
Patient Information
Vemlidy ® (VEM-lih-dee)
(tenofovir alafenamide)
tablets
|
|
Read this Patient Information before you start taking
Vemlidy and each time you get a refill. There may be new information. This
information does not take the place of talking with your healthcare provider
about your medical condition or treatment.
|
|
What is the most important
information I should know about Vemlidy?
Vemlidy can cause serious side effects, including:
|
|
· Worsening of hepatitis B infection. Your hepatitis B (HBV) infection may become worse (flare-up) if
you take Vemlidy and then stop taking it. A "flare-up" is when your
HBV infection suddenly returns in a worse way than before.
o Do not run out of Vemlidy. Refill your prescription or
talk to your healthcare provider before your Vemlidy is all gone.
o Do not stop taking Vemlidy without first talking to your
healthcare provider.
o If you stop taking Vemlidy, your healthcare provider
will need to check your health often and do blood tests regularly for several
months to check your HBV infection. Tell your healthcare provider about any
new or unusual symptoms you may have after you stop taking Vemlidy.
|
|
For more information about
side effects, see the section " What are the possible side effects of Vemlidy?"
|
|
What is Vemlidy?
Vemlidy is a prescription medicine used to treat chronic (long-lasting)
hepatitis B virus (HBV) in adults with stable (compensated) liver disease.
Vemlidy may lower the amount of HBV in your
body.Vemlidy may improve the condition of your liver.
It is not known if Vemlidy is safe and effective in
children under 18 years of age.
|
|
What should I tell my
healthcare provider before taking Vemlidy?
Before you take
Vemlidy, tell your healthcare provider about all of your medical conditions,
including if you:
have HIV-1 infection. Your healthcare provider
may test you for HIV infection before starting Vemlidy. If you have HIV
and take Vemlidy, the HIV virus may develop resistance and become harder
to treat.have end stage renal disease (ESRD).are pregnant or plan to become pregnant. It is
not known if Vemlidy will harm your unborn baby. Tell your healthcare
provider if you become pregnant during treatment with Vemlidy.
Pregnancy
Registry: There is a
pregnancy registry for women who take antiviral medicines during pregnancy.
The purpose of this registry is to collect information about the health
of you and your baby. Talk with your healthcare provider about how you
can take part in this registry.are breastfeeding or plan to breastfeed. It is
not known if Vemlidy passes into your breast milk. Talk with your
healthcare provider about the best way to feed your baby.
Tell your healthcare
provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins,
and herbal supplements.
Some medicines may affect how Vemlidy works.
Keep a list of your medicines and show it to
your healthcare provider and pharmacist when you get a new medicine. You
can ask your healthcare provider or pharmacist for a list of medicines
that interact with Vemlidy.Do not start a new
medicine without telling your healthcare provider. Your healthcare provider can tell you if
it is safe to take Vemlidy with other medicines.
|
|
How should I take Vemlidy?
Take Vemlidy exactly as your healthcare
provider tells you to take it.Take Vemlidy 1 time each day.Take Vemlidy with food.Do not change your dose or stop taking Vemlidy
without first talking with your healthcare provider. Stay under a
healthcare provider's care when taking Vemlidy.Do not miss a dose of Vemlidy.If you take too much Vemlidy, call your
healthcare provider or go to the nearest hospital emergency room right
away.When your Vemlidy supply starts to run low, get
more from your healthcare provider or pharmacy. This is very important
because your HBV infection may get worse (flare-up) if you stop taking
Vemlidy.
|
|
What are the possible side
effects of Vemlidy?
Vemlidy may
cause serious side effects, including:
See " What is the most important information I should
know about Vemlidy?"New or worse kidney
problems, including kidney failure. Your healthcare provider may do blood and
urine tests to check your kidneys before you start and while you are
taking Vemlidy. Your healthcare provider may tell you to stop taking
Vemlidy if you develop new or worse kidney problems.Too much lactic acid in
your blood (lactic acidosis). Too
much lactic acid is a serious but rare medical emergency that can lead
to death. Tell your healthcare provider right away if you get these
symptoms: weakness or being more tired than usual, unusual muscle pain,
being short of breath or fast breathing, stomach pain with nausea and
vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a
fast or abnormal heartbeat.Severe liver problems. In rare cases, severe liver problems can
happen that can lead to death. Tell your healthcare provider right away
if you get these symptoms: skin or the white part of your eyes turns
yellow, dark "tea-colored" urine, light-colored stools, loss
of appetite for several days or longer, nausea, or stomach-area pain.
The most common side effects of Vemlidy are:
|
|
· headache
· stomach pain
|
· tiredness
· cough
|
· nausea
· back pain
|
|
Tell your healthcare provider if you have any side
effect that bothers you or that does not go away.
These are not all the possible side effects of Vemlidy. For more information,
ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
|
|
How should I store Vemlidy?
Store Vemlidy below 86 °F (30 °C).Keep Vemlidy in its original container.Keep the container tightly closed.
Keep Vemlidy and all
medicines out of reach of children.
|
|
General information about
the safe and effective use of Vemlidy.
Medicines are sometimes prescribed for purposes other than those listed in a
Patient Information leaflet. Do not use Vemlidy for a condition for which it
was not prescribed. Do not give Vemlidy to other people, even if they have
the same symptoms you have. It may harm them. If you would like more
information, talk with your healthcare provider. You can ask your healthcare
provider or pharmacist for information about Vemlidy that is written for
health professionals.
|
|
What are the ingredients in
Vemlidy?
Active
ingredients: tenofovir alafenamide
Inactive
ingredients: croscarmellose sodium,
lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The
tablets are film-coated with a coating material containing: iron oxide
yellow, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
Manufactured and distributed by: Gilead Sciences, Inc. Foster City, CA 94404
Vemlidy is a trademark of Gilead Sciences, Inc., or its related companies. ©
2017 Gilead Sciences, Inc. All rights reserved.
208464-GS-001
For more information, call 1-800-445-3235 or go to www.Vemlidy.com.
|
|
|
|
|
PRINCIPAL
DISPLAY PANEL - 25 mg Tablet Bottle Label
NDC 61958- 2301-1
30 tablets
Vemlidy®
(tenofovir alafenamide)
tablets, 25 mg
Note to
pharmacist:
Do not cover ALERT box with pharmacy label.
ALERT: Find out
about medicines that
should NOT be taken with Vemlidy
|
Vemlidy tenofovir
alafenamide tablet
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:61958-2301
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
TENOFOVIR ALAFENAMIDE
FUMARATE (TENOFOVIR
ANHYDROUS)
|
TENOFOVIR ALAFENAMIDE
|
25 mg
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
LACTOSE MONOHYDRATE
|
|
|
MICROCRYSTALLINE CELLULOSE
|
|
|
CROSCARMELLOSE SODIUM
|
|
|
MAGNESIUM STEARATE
|
|
|
POLYVINYL ALCOHOL,
UNSPECIFIED
|
|
|
TITANIUM DIOXIDE
|
|
|
POLYETHYLENE GLYCOL 3350
|
|
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TALC
|
|
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FERRIC OXIDE YELLOW
|
|
|
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Product Characteristics
|
|
Color
|
yellow
|
Score
|
no score
|
|
Shape
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ROUND
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Size
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8mm
|
|
Flavor
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|
Imprint Code
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GSI;25
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Contains
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|
|
|
|
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Packaging
|
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#
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Item Code
|
Package Description
|
|
|
1
|
NDC:61958-2301-1
|
30 TABLET in 1 BOTTLE, PLASTIC
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|
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Marketing Information
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|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA208464
|
11/10/2016
|
|
|
|
Labeler - Gilead Sciences, Inc. (185049848)
|
Revised: 10/2017
Gilead Sciences,
Inc
