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Serious and sometimes fatal
hypersensitivity reactions have occurred with abacavir-containing
products
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Hypersensitivity to abacavir is
a multi-organ clinical syndrome
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Patients who carry the
HLA-B*5701 allele are at a higher risk of experiencing a
hypersensitivity reaction to abacavir, although hypersensitivity
reactions have occurred in patients who do not carry the HLA-B*5701
allele
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TRIUMEQ is contraindicated in
patients with a prior hypersensitivity reaction to abacavir and in
HLA-B*5701-positive patients. All patients should be screened for
the HLA-B*5701 allele prior to initiating therapy or reinitiation
of therapy with TRIUMEQ unless patients have a previously
documented HLA-B*5701 allele assessment
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Discontinue TRIUMEQ as soon as
hypersensitivity reaction is suspected. Regardless of HLA-B*5701
status, permanently discontinue TRIUMEQ if hypersensitivity cannot
be ruled out, even when other diagnoses are
possible
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Following a hypersensitivity
reaction to TRIUMEQ, NEVER restart TRIUMEQ or any other
abacavir-containing produc
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Severe acute exacerbations of
HBV have been reported in patients who are co-infected with HBV and
HIV-1 and have discontinued lamivudine, a component of TRIUMEQ.
Monitor hepatic function closely in these patients and, if
appropriate, initiate anti-hepatitis B
treatment
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Do not use TRIUMEQ in patients who have the
HLA-B*5701 allele
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Do not use TRIUMEQ in patients with previous
hypersensitivity reaction to abacavir, dolutegravir, or
lamivudine
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Do not use TRIUMEQ in patients receiving
dofetilide
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Do not use TRIUMEQ in patients with moderate or
severe hepatic impairment
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Hypersensitivity reactions have been reported with
dolutegravir and were characterized by rash, constitutional
findings, and sometimes organ dysfunction, including liver
injury
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Clinically, it is not possible to determine
whether a hypersensitivity reaction with TRIUMEQ would be caused by
abacavir or dolutegra
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Discontinue TRIUMEQ immediately if signs or
symptoms of hypersensitivity reactions develop, as a delay in
stopping treatment may result in a life-threatening reaction.
Clinical status, including liver aminotransferases, should be
monitored and appropriate therapy
initiated
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Hepatic adverse events have been reported,
including cases of hepatic toxicity (elevated serum liver
biochemistries, hepatitis, and acute liver failure), in patients
receiving a dolutegravir-containing regimen without pre-existing
hepatic disease or other identifiable risk
factors
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Patients with underlying hepatitis B or C or
marked elevations in transaminases prior to treatment may be at
increased risk for worsening or development of transaminase
elevations with use of TRIUMEQ. In some cases, the elevations in
transaminases were consistent with immune reconstitution syndrome
or hepatitis B reactivation, particularly in the setting where
anti-hepatitis therapy was withdrawn
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Drug-induced liver injury leading to liver
transplant has been reported with
TRIUMEQ
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Monitoring for hepatotoxicity is
recommended
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Avoid use of dolutegravir, a component of TRIUMEQ,
at the time of conception through the first trimester due to the
risk of neural tube defects
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Perform pregnancy testing before use of
dolutegravir and advise that consistent use of effective
contraception is recommended while using dolutegravir in
adolescents and adults of childbearing
potential
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Several observational studies have reported an
association with the use of abacavir and the risk of MI;
meta-analyses of randomized controlled clinical trials did not show
increased risk. To date, there is no established biological
mechanism to explain a potential increase in risk. In totality, the
available data show inconsistency; therefore, evidence for a causal
relationship between abacavir and the risk of MI is
inconclusive
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The underlying risk of coronary heart disease
should be considered when prescribing antiretroviral therapies,
including abacavir, and action taken to minimize all modifiable
risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus,
smoking)
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Coadministration of TRIUMEQ with drugs that induce
or inhibit UGT1A1 and/or CYP3A may affect plasma
concentrations
|
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Administer TRIUMEQ 2 hours before or 6 hours
after taking antacids, polyvalent cation-containing products or
laxatives, sucralfate, oral supplements containing iron or calcium,
or buffered medications Alternatively, TRIUMEQ and supplements
containing calcium and iron can be taken with a
meal
|
|
●
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Consult the full Prescribing Information for
TRIUMEQ for more information on potentially significant drug
interactions, including clinical
comments
|
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Pregnancy: There are insufficient human data on the use
of TRIUMEQ during pregnancy to definitively assess a
drug-associated risk for birth defects and miscarriage. An
Antiretroviral Pregnancy Registry has been established. Avoid use
of dolutegravir, a component of TRIUMEQ, at the time of conception
through the first trimester of pregnancy. If planning a pregnancy
or if pregnancy is confirmed while taking dolutegravir during the
first trimester, if possible, switch to an alternative
regimen
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●
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Lactation: Breastfeeding is not recommended due to the
potential for HIV-1 transmission, developing viral resistance in
HIV-positive infants, and adverse reactions in a breastfed
infant
|
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Females and Males of
Reproductive Potential: Perform pregnancy testing before initiation of
dolutegravir. Advise adolescents and adults of childbearing
potential to consistently use effective contraception while taking
dolutegravir
|
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Patients with Impaired Renal
Function: TRIUMEQ is not
recommended in patients with creatinine clearance <50
mL/min
|
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●
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Patients with Impaired Hepatic
Function: If a dose
reduction of abacavir is required for patients with mild hepatic
impairment, then the individual components of TRIUMEQ should be
used
|
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More EDURANT®-treated
subjects with HIV-1 RNA greater than 100,000 copies/mL at the start
of therapy experienced virologic failure (HIV-1 RNA ≥50
copies/mL) compared to EDURANT®-treated
subjects with HIV-1 RNA less than or equal to 100,000
copies/mL
|
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●
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Coadministration of EDURANT® with
the following drugs is contraindicated because significant
decreases in rilpivirine plasma concentrations may occur due to
CYP3A enzyme induction or gastric pH increase, which may result in
loss of virologic response and possible resistance and
cross-resistance: carbamazepine, oxcarbazepine, phenobarbital,
phenytoin, rifampin, rifapentine, proton pump inhibitors such as
esomeprazole, lansoprazole, omeprazole, pantoprazole, and
rabeprazole, systemic dexamethasone (more than single dose), and
products containing St. John's wort (Hypericum
perforatum)
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●
|
Skin and Hypersensitivity
Reactions: Severe skin and
hypersensitivity reactions have been reported during the
postmarketing experience, including cases of Drug Reaction with
Eosinophilia and Systemic Symptoms (DRESS), with
rilpivirine-containing regimens. While some skin reactions were
accompanied by constitutional symptoms such as fever, other skin
reactions were associated with organ dysfunctions, including
elevations in hepatic serum biochemistries.
EDURANT® should
be discontinued immediately if signs or symptoms of severe skin or
hypersensitivity reactions develop, including but not limited to,
severe rash or rash accompanied by fever, blisters, mucosal
involvement, conjunctivitis, facial edema, angioedema, hepatitis or
eosinophilia. Clinical status including laboratory parameters
should be monitored and appropriate therapy should be
initiated
|
|
●
|
Hepatotoxicity: Hepatic
adverse events were reported. Patients with underlying hepatic
disease, including hepatitis B or C, or marked elevations in
transaminases before treatment may be at increased risk for
worsening or development of transaminase elevations. Monitor liver
function tests (LFTs) before and during treatment. A few
hepatotoxicity cases occurred in patients with no pre-existing
hepatic disease or other identifiable risk factors; therefore,
monitoring of LFTs should be considered in all
patients
|
|
●
|
Depressive Disorders:
Severe depressive disorders, defined
as depressed mood, depression, dysphoria, major depression, mood
altered, negative thoughts, suicide attempt, and suicidal ideation,
have been reported with EDURANT®.
Immediate medical evaluation is recommended for severe depressive
symptoms
|
|
●
|
Fat
Redistribution: Redistribution and/or accumulation of body fat
have been observed in patients receiving ARV therapy. The causal
relationship, mechanism, and long-term consequences of these events
have not been established
|
|
●
|
Immune Reconstitution
Syndrome has been reported
in patients treated with combination ARV therapy, including
EDURANT®.
Autoimmune disorders (such as Graves disease, polymyositis, and
Guillain-Barré syndrome) have also been reported to occur in
the setting of immune reconstitution; however, the time to onset is
more variable and can occur many months after initiation of
treatment
|
|
●
|
EDURANT® should
be used with caution when coadministered with drugs that may reduce
the exposure of rilpivirine, such as antacids and
H2-receptor
antagonists
|
|
●
|
Concomitant use of EDURANT® with
rifabutin may cause a decrease in the plasma concentrations of
rilpivirine. Please read the Dosage and Administration Section of
the Prescribing Information for more details regarding the
concomitant use of EDURANT® and
rifabutin
|
|
●
|
EDURANT® should
be used with caution when coadministered with a drug with a known
risk of Torsade de Pointes
|
|
●
|
EDURANT® should
not be used in combination with NNRTIs
|
|
●
|
Hepatic Impairment: EDURANT® should be used with caution in patients with severe hepatic impairment (Child-Pugh Class C) as pharmacokinetics of EDURANT® have not been evaluated in these patients |
|
●
|
Pregnancy: In a clinical trial, total rilpivirine
exposures were generally lower during pregnancy compared to the
postpartum period
|
|
●
|
Lactation: Women infected with HIV should be instructed
not to breastfeed due to the potential for HIV
transmission
|
|
●
|
The most common adverse drug reactions reported
(incidence >2%) of at least moderate intensity (≥ Grade 2)
in patients taking EDURANT® through
96 weeks were depressive disorders (5%), headache (3%), insomnia
(3%), and rash (3%)
|
|
ViiV
Healthcare Media enquiries:
|
Melinda
Stubbee
|
+1 919
491 0831
|
|
|
Audrey
Abernathy
|
+1 919
605 4521
|
|
|
|
|
|
GSK
Global Media enquiries:
|
Simon
Steel
|
+44 (0)
20 8047 5502
|
|
|
Sarah
Spencer
|
+1 215
751 3335
|
|
Analyst/Investor
enquiries:
|
Sarah
Elton-Farr
|
+44 (0)
20 8047 5194
|
|
|
Mel
Foster-Hawes
|
+44 (0)
20 8047 0674
|
|
|
Danielle
Smith
James
Dodwell
|
+44 (0)
20 8047 7562
+44 (0)
20 8047 2406
|
|
|
Jeff
McLaughlin
|
+1 215
751 7002
|
|
|
GlaxoSmithKline plc
|
|
|
(Registrant)
|
|
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|
|
Date: October
30, 2018
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By: VICTORIA
WHYTE
--------------------------
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|
Victoria Whyte
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|
|
Authorised
Signatory for and on
|
|
|
behalf
of GlaxoSmithKline plc
|