Upload
others
View
4
Download
0
Embed Size (px)
Citation preview
Non-Inferior Efficacy of Dolutegravir▼(DTG) plusLamivudine (3TC) vs DTG plus Tenofovir/Emtricitabine (TDF/FTC) Fixed-Dose Combination in Antiretroviral Treatment–Naive Adults with HIV-1 Infection
Week 48 Results from the GEMINI-1 & GEMINI-2 Studies
UK/DTG3TC /0019/18(1) November 2018
Prescribing information can be found at the end of this presentation
Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Why investigate a 2-drug regimen?
No one should take more medicine than they need
A 20-year old starting a 3-drug regimen (3DR) may be on therapy for nearly 6
decades, which translates to more that 60,000 doses of individual medications.1
Managing comorbidities, DDIs and potential long-term effects of treatment are
important considerations
1. The Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort
studies. Lancet HIV. 2017;4(8):e349-e356
2. Marcotullio S, et al. EACS 2017, poster PE25/9
ARV, antiretroviral; PLHIV, people living with HIV
The Positive Perspectives Survey highlighted that 72% (n=783/1085) of
PLHIV worry about the long-term impact of their medicines on their bodies2
The potential benefits associated with 2-drug regimens (2DRs) include
reduced ARV exposure and potential for toxicities, drug preservation for
future treatment options and increased treatment access
3DRs achieve viral suppression by targeting two different intracellular viral
replication processes; 2DRs can be expected to achieve the same as they also
target two distinct viral replication processes
• The requirement for lifelong ART for HIV infection has highlighted interest in
2DRs to minimize cumulative drug exposure1
• Lower ARV exposure may translate to less long-term drug toxicity
• The potency, safety and high resistance barrier of DTG make it an optimal core
agent for 2DRs
• The safety, tolerability and efficacy of 3TC make it a reliable partner for initial
HIV-1 treatment
• Previous pilot studies have evaluated DTG + 3TC as a complete 2DR in
treatment-naive participants
– PADDLE: 90% (18/20) had VL <50 c/mL at Week 482
– ACTG A5353: 90% (108/120) had VL <50 c/mL at Week 243
• DTG + 3TC was evaluated vs a 3-drug regimen (3DR) DTG + TDF/FTC for
treatment-naive patients with HIV-1 infection through 48 weeks
Introduction
1. Kelly et al. Drugs. 2016;76(5):523-531.
2. Cahn et al. J Int AIDS Soc. 2017;20(1):21678.
3. Taiwo et al. Clin Infect Dis. 2018;66(11):1689-1697.
ART, antiretroviral therapy
a−10% noninferiority margin for individual studies.
GEMINI-1 and -2 Phase III Study Design
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
DTG + 3TC (N=716)
Day
1
Screening
(28 d)
Identically designed, randomized, double-blind, parallel-group,
multicenter, noninferiority studies
DTG + TDF/FTC (N=717)
DTG + 3TC
Week
48
Primary endpoint
at Week 48:
participants with
HIV-1 RNA <50 c/mL
(ITT-E snapshot)a
Double-blind
phase
Open-label
phase
Continuation
phase
CountriesArgentina Australia Belgium
Canada France Germany
Italy Republic of Korea Mexico
Netherlands Peru Poland
Portugal Romania Russian Federation
South Africa Spain Switzerland
Taiwan United Kingdom United States
China
Week
144
Week
24
Week
96
• ART-naive adults
• VL 1000-500,000 c/mL
1:1
Eligibility criteria• ≤10 days of prior ART
• No evidence of pre-existing viral resistance
based on presence of any major resistance-
associated mutation
• No HBV infection or need for HCV therapy
Baseline stratification factors: plasma HIV-1 RNA (≤100,000 c/mL vs >100,000 c/mL) CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3).
Demographic and Baseline Characteristics
for the Pooled GEMINI-1 and -2 Population
Characteristic
DTG + 3TC
(N=716)
DTG + TDF/FTC
(N=717)
Age, median (range), y
≥50 y, n (%)
32.0 (18-72)
65 (9)
33.0 (18-70)
80 (11)
Female, n (%) 113 (16) 98 (14)
Race, n (%)
African American/African heritage
Asian
White
Other
Ethnicity, n (%)
Hispanic or Latino
Not Hispanic or Latino
99 (14)
71 (10)
480 (67)
66 (9)
215 (30)
501 (70)
76 (11)
72 (10)
497 (69)
72 (10)
232 (32)
485 (68)
HIV-1 RNA, median (range), log10 c/mL
≤100,000
>100,000a
4.43 (1.59-6.27)
576 (80)
140 (20)
4.46 (2.11-6.37)
564 (79)
153 (21)
CD4+ cell count, median (range), cells/mm3
>200
≤200
427.0 (19-1399)
653 (91)
63 (9)
438.0 (19-1497)
662 (92)
55 (8)
a2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL and were included in the ITT-E analysis.
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
-10 -8 -6 -4 -2 0 2 4 6 8 10
Snapshot Outcomes at Week 48for GEMINI-1
aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1
RNA (≤100,000 c/mL vs >100,000 c/mL) and CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3).
Virologic outcome Adjusted treatment difference (95% CI)a
Percentage-point difference
DTG + TDF/FTC
-6.7 1.5
GEMINI-1 -2.6
DTG + TDF/FTC DTG + 3TC
90
4 6
93
26
0
20
40
60
80
100
Virologicsuccess
Virologicnonresponse
No virologicdata
HIV
-1 R
NA
<50
c/m
L, %
GEMINI-1 DTG + 3TC (N=356) DTG + TDF/FTC (N=358)
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
-10 -8 -6 -4 -2 0 2 4 6 8 10
Snapshot Outcomes at Week 48for GEMINI-1 and -2
aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1
RNA (≤100,000 c/mL vs >100,000 c/mL) and CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3).
Virologic outcome Adjusted treatment difference (95% CI)a
Percentage-point difference
DTG + 3TC is non-inferior to DTG +
TDF/FTC with respect to proportion
<50 c/mL at Week 48 (snapshot, ITT-E
population) in both studies
DTG + TDF/FTC
-6.7 1.5
-4.3 2.9
GEMINI-1
GEMINI-2 -0.7
-2.6
DTG + TDF/FTC DTG + 3TC
90
4 6
93
26
93
25
94
2 4
0
20
40
60
80
100
Virologicsuccess
Virologicnonresponse
No virologicdata
HIV
-1 R
NA
<50
c/m
L, %
GEMINI-1 DTG + 3TC (N=356) DTG + TDF/FTC (N=358)
GEMINI-2 DTG + 3TC (N=360) DTG + TDF/FTC (N=359)
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Snapshot Analysis by Visit: Pooled ITT-E Population
0
70
85 89
90
93
91 93
72
87 89
88
93
9091
-20
0
20
40
60
80
100
-4 0 4 8 12 16 20 24 28 32 36 40 44 48
HIV
-1 R
NA
<50 c
/mL, %
a
Study visit (weeks)
DTG + 3TC (n=716)
DTG + TDF/FTC (n=717)
aCalculated from a repeated measures model adjusting for study, treatment, visit (repeated factor), baseline plasma HIV -1 RNA,
baseline CD4+ cell count, treatment and visit interaction, and baseline CD4+ cell count and visit interaction.
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Pooled Snapshot Outcomes at Week 48: ITT-E Population
aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1
RNA (≤100,000 c/mL vs >100,000 c/mL), CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3), and study (GEMINI-1 vs GEMINI-2).
Virologic outcome Adjusted treatment difference (95% CI)a
DTG + TDF/FTC DTG + 3TC
-10 -8 -6 -4 -2 0 2 4 6 8 10
-4.4 1.1
-1.7
Percentage-point difference
ITT-E
91
36
93
25
0
20
40
60
80
100
Virologicsuccess
Virologicnonresponse
No virologicdata
HIV
-1 R
NA
<50
c/m
L, %
ITT-E DTG + 3TC (N=716) DTG + TDF/FTC (N=717)
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Pooled Snapshot Outcomes at Week 48: ITT-E and Per Protocol Populations
aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1
RNA (≤100,000 c/mL vs >100,000 c/mL), CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3), and study (GEMINI-1 vs GEMINI-2). bPP, per protocol: population consisted of participants in the ITT-E population except for significant protocol violators, which could
potentially affect efficacy outcomes as determined by the medical monitor prior to database lock.
Virologic outcome Adjusted treatment difference (95% CI)a
DTG + TDF/FTC DTG + 3TC
-10 -8 -6 -4 -2 0 2 4 6 8 10
-4.4 1.1
-1.7
Percentage-point difference
DTG + 3TC is non-inferior to DTG +
TDF/FTC with respect to proportion
<50 c/mL at Week 48 (snapshot, ITT-E
population) in both studies
-1.3
-3.9 1.2
ITT-E
PP
91
36
93
25
93
25
94
14
0
20
40
60
80
100
Virologicsuccess
Virologicnonresponse
No virologicdata
HIV
-1 R
NA
<50
c/m
L, %
ITT-E DTG + 3TC (N=716) DTG + TDF/FTC (N=717)
PPb DTG + 3TC (N=694) DTG + TDF/FTC (N=693)
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Pooled Outcomes at Week 48 Stratified by Baseline HIV-1 RNA: ITT-E Analysis
91 9394 9392
79
9093
0
20
40
60
80
100
HIV
-1 R
NA
<5
0 c
/mL
, %
ITT-E Analysis
• 2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL
DTG + 3TC DTG + TDF/FTC
>100,000≤100,000 >200 ≤200
Baseline HIV-1
RNA, c/mL
Baseline CD4+
cell count, cell/mm3
526
576
531
564
129
140
138
153
605
653
618
662
50
67
51
55
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Pooled Outcomes at Week 48 Stratified by Baseline HIV-1 RNA and CD4+ Cell Count: ITT-E Analysis
91 9394 9392
79
9093
0
20
40
60
80
100
HIV
-1 R
NA
<5
0 c
/mL
, %
ITT-E Analysis
• 2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL
DTG + 3TC DTG + TDF/FTC
>100,000≤100,000 >200 ≤200
Baseline HIV-1
RNA, c/mL
Baseline CD4+
cell count, cell/mm3
526
576
531
564
129
140
138
153
605
653
618
662
50
63
51
55
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
98 9898 9899 9897 100
0
20
40
60
80
100
Wit
ho
ut
TR
DF,
%
TRDF Analysis
566
576
>100,000≤100,000 >200 ≤200
Baseline HIV-1
RNA, c/mL
Baseline CD4+
cell count, cell/mm3
Pooled Outcomes at Week 48 Stratified by Baseline HIV-1 RNA
and CD4+ Cell Count: ITT-E and Pre-planned TRDF Analysis
91 9394 9392
79
9093
0
20
40
60
80
100
HIV
-1 R
NA
<5
0 c
/mL
, %
ITT-E Analysis
• 2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL
• Treatment related discontinuation = failure (TRDF) population accounts for confirmed virologic withdrawal (CVW), withdrawal
due to lack of efficacy, withdrawal due to treatment-related AE, and participants who met protocol-defined stopping criteria
• DTG + 3TC CD4 <200 Snapshot non-response: 1 CVW, 2 discontinued due to AE (TB, Chagas disease); 4 with VL >50 in
window, 3 of 4 re-suppressed; 2 protocol violations, 1 withdrew consent, 1 withdrew to start HCV treatment
DTG + 3TC DTG + TDF/FTC
>100,000≤100,000 >200 ≤200
Baseline HIV-1
RNA, c/mL
Baseline CD4+
cell count, cell/mm3
553
564
138
140
149
153
642
653
647
662
62
63
55
55
526
576
531
564
129
140
138
153
605
653
618
662
50
63
51
55
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Confirmed Virologic Withdrawals Through Week 48: ITT-E Population
GEMINI 1 GEMINI 2 Pooled
Variable, n (%)
DTG + 3TC
(N=356)
DTG +
TDF/FTC
(N=358)
DTG + 3TC
(N=360)
DTG +
TDF/FTC
(N=359)
DTG + 3TC
(N=716)
DTG +
TDF/FTC
(N=717)
CVW 4 (1) 2 (<1) 2 (<1) 2 (<1) 6 (<1) 4 (<1)
Treatment-emergent
resistance
0 0 0 0 0 0
• Low rates of virologic withdrawals were observed at Week 48
• No treatment-emergent INSTI mutations or NRTI mutations were
observed among participants who met CVW (confirmed virologic
failure) criteria
Confirmed virologic withdrawal criteria is defined as a second and consecutive HIV-1 RNA value meeting virologic non-response or rebound. Virologic non-response is defined as either a decrease in
plasma HIV-1 RNA of less than 1 log10 c/mL by Week 12 with subsequent confirmation unless plasma HIV-1 RNA is <200 c/mL, or confirmed plasma HIV-1 RNA levels ≥200 c/mL on or after Week 24.
Virologic rebound is defined as confirmed rebound in plasma HIV-1 RNA levels to ≥200 c/mL after prior confirmed suppression to <200 c/mL.
.Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Adverse Events: Pooled ITT-E Population
n (%)
DTG +
3TC
(N=716)
DTG +
TDF/FTC
(N=717)
Any AE 543 (76) 579 (81)
AE occurring in ≥5% of participants in either group
Headache
Diarrhea
Nasopharyngitis
Upper respiratory tract infection
Nausea
Insomnia
Pharyngitis
Back pain
71 (10)
68 (9)
55 (8)
56 (8)
27 (4)
27 (4)
36 (5)
35 (5)
75 (10)
77 (11)
78 (11)
44 (6)
53 (7)
45 (6)
32 (4)
31 (4)
Drug-related AE
Grade 2-4 AE occurring in ≥1% of participants
Headache
126 (18)
42 (6)
8 (1)
169 (24)
47 (7)
8 (1)
AE leading to withdrawal from the study
Neuropsychiatric AEs leading to withdrawal
15 (2)
6 (<1)
16 (2)
4 (<1)
Any serious AEa 50 (7) 55 (8)
a2 deaths (acute myocardial infarction, n=1; Burkitt’s lymphoma, n=1) in the GEMINI-2 study; both were in the DTG + 3TC group and were
considered unrelated to the study drug regimen.
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Adverse Events Leading to Withdrawal:
Pooled ITT-E Population
Cahn et al. AIDS 2018; Amsterdam, the Netherlands. Slides TUAB0106LB.
n (%)
DTG + 3TC
(N=716)
DTG + TDF/FTC
(N=717)
Participants with AEs leading to withdrawal from the study 15 (2) 16 (2)
All events leading to withdrawal (participant may report >1 AE)Hepatitis AAlcoholic hepatitisAcute hepatitis CHepatoxicityDrug-induced liver injuryHepatitis CRenal impairmentCreatinine renal clearance decreasedGlomerular filtration rate decreasedAnxietyDepressionSuicide attemptSuicidal ideationInsomniaSleep disorderPsychotic disorderSubstance-induced psychotic disorderOverdoseAlcoholic psychosisAcute myocardial infarctionBurkitt’s lymphoma Non-Hodgkin’s lymphomaB-cell lymphomaPulmonary tuberculosisTuberculous pleurisyOsteoporosisRhabdomyolysis
2 (<1)1 (<1)1 (<1)1 (<1)
00
1 (<1)00
1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)
00
1 (<1)1 (<1)
00
1 (<1)1 (<1)
00
1 (<1)1 (<1)1 (<1)
01 (<1)1 (<1)2 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)
0000
1 (<1)1 (<1)
00
1 (<1)1 (<1)
00
1 (<1)1 (<1)
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Change in Renal Biomarkers at Week 48: Pooled ITT-E Population
6,3
10,4
-12,1
4,1
13,5
-15,5
-20
-15
-10
-5
0
5
10
15
Ad
jus
ted
me
an
ch
an
ge f
rom
ba
se
lin
ea
eGFR from
cystatin C,
CKD-EPI
(mL/min/
1.73 m2)
eGFR from
creatinine,
CKD-EPI
(mL/min/1.73 m2)
Creatinine
(µmol/L)
aEstimated mean change from baseline at Week 48 in each arm calculated from ANCOVA model adjusting for: study, treatment, baseline
plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, and baseline
biomarker value. Multiple imputed dataset (missing at random). bEstimated from geometric mean ratio for baseline and Week 48.
Plasma/Serum markers
-13,1
-7,4 -7,7
2,9
11,4
31,2
-20
-10
0
10
20
30
40
Ch
an
ge f
rom
ba
se
lin
e, %
b
Urine markers
Protein/
Creatinine
(g/mol)
Retinol-binding
protein/
Creatinine
(µg/mmol)
Beta-2
microglobulin/
Creatinine
(mg/mmol)
DTG + 3TC (n=716) DTG + TDF/FTC (n=717)
*
*
*
*
*
*
*p<0.001a
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Change in Bone Markers at Week 48: Pooled ITT-E Population
1,220,60 0,40 0,14
4,07
6,17
13,10
0,330
5
10
15
Serum bone specificalkaline phosphatase
Serumosteocalcin
Serum procollagen 1N-terminal propeptide
Serum type 1 collagenC-telopeptide
Ad
jus
ted
me
an
ch
an
ge
fro
m
baseli
ne (
µg
/L)a
aEstimated mean change from baseline at Week 48 in each arm calculated from ANCOVA model adjusting for study, treatment, baseline
plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, BMI, smoking status, current vitamin D use, and baseline biomarker value.
Multiple imputed dataset (missing at random).
DTG + 3TC (n=716)
DTG + TDF/FTC (n=717)
*
*
*
*
*p<0.001
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
Change in Serum Lipids at Week 48: Pooled ITT-E Population
0
1
2
3
4
5
Ad
jus
ted
me
an
va
lue
a
Total
cholesterol
(mmol/L)
LDL
cholesterol
(mmol/L)
Total cholesterol/
HDL cholesterol
ratio
HDL
cholesterol
(mmol/L)
Triglycerides
(mmol/L)
DTG + 3TC (n=716)
DTG + TDF/FTC (n=717)
0.320.15
0.15
0.17
0.03
0.12
0.14
0.08
0.24
0.02
****p<0.001
**
**
*
*
*p<0.05
aThe adjusted mean is the estimated mean change from baseline in each fasting lipid at Week 48 in each arm calculated from an ANCOVA model adjusting for the
following covariates/factors: study treatment, baseline plasma HIV-1 RNA, baseline CD4+ cell count, age and fasting lipids at baseline. Multiple imputed dataset
(missing at random). Absolute values based on summaries. Baseline values are represented by the main legend colors, with changes at Week 48 represented by
shaded areas (increases) or dashed lines (decreases).
Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
• GEMINI-1 and GEMINI-2 results demonstrate non-inferior virologic efficacy for
the 2DR DTG + 3TC vs a 3DR DTG + TDF/FTC at Week 48
• Both DTG + 3TC and DTG + TDF/FTC were associated with low rates of
confirmed virologic withdrawals through Week 48
– No treatment-emergent INSTI or NRTI mutations were observed among participants
who met CVW criteria
• Overall safety and tolerability profile at Week 48 was comparable between the
2 regimens
– Fewer drug-related AEs with DTG + 3TC
– Statistically significant change in renal and bone biomarkers from baseline favours
DTG + 3TC vs DTG + TDF/FTC
• GEMINI-1 and GEMINI-2 data support DTG + 3TC as a 2DR for the treatment of
HIV-1 infection in treatment-naïve HBV-negative patients with viral loads up to
500,000 copies/mL
Conclusions
Prescribing Information
Tivicay▼ dolutegravir 10mg, 25mg and 50mg tablets See Summary of Product Characteristics before prescribing
Indication: HIV in >6 years and >15kg as part of combination therapy. Dosing: Adults & adolescents >40kg: 50mg once daily with or without food if no proven/ suspected integrase resistance. Children 6 to <12 years: dose according to bodyweight: 15-<20kg: 20mg once daily (2x10mg); 20-<30kg: 25mg once daily; 30-<40kg: 35mg once daily (1 x 25mg + 1 x 10mg); When co-administered with efavirenz, nevirapine, tipranavir/ritonavir, etravirine (without boosted PI), carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John’s Wort or rifampicin, Tivicay 50mg twice daily in adults/adolescents or the weight-based once daily dose twice daily in paediatric patients. Adults with proven or suspected integrase resistance: 50mg twice daily preferably with food. Limited data in paediatric patients with proven/suspected integrase resistance. Elderly: Limited data in 65+ yrs. Caution in severe hepatic impairment. Contraindications: Hypersensitivity to any ingredient. Co-administration with dofetilide. Warnings/precautions: Risk of hypersensitivity reactions. Discontinue dolutegravir and other suspect agents immediately if suspected. The two-drug regimen of dolutegravir and lamivudine is only suitable for the treatment of HIV-1 infection where there is no known or suspected resistance to the integrase inhibitor class, or to lamivudine. Risks of osteonecrosis, immune reactivation syndrome. Monitor LFTs in Hepatitis B/C co-infection and ensure
effective Hepatitis B therapy. Caution with metformin: monitor renal function and consider metformin dose adjustment. Use with etravirine requires boosted PI or increased dose of dolutegravir. Use with Mg/Al-containing antacids, calcium, multivitamins or iron requires dosage separation. Pregnancy/ lactation: Not recommended. Avoid breast-feeding. Side effects: See SmPC for full details. Headache, GI disturbance, insomnia, abnormal dreams, depression, anxiety, dizziness, rash, pruritus, fatigue, elevations of ALT, AST and CPK, arthralgia, myalgia, hypersensitivity, suicidal ideation or suicide attempt, acute hepatic failure. Basic NHS costs: £498.75 for 30 x 50mg tablets EU/1/13/892/001. £99.75 for 30 x 10mg tablets (EU/1/13/892/003). £249.38 for 30 x 25mg tablets (EU/1/13/892/005). MA holder: ViiV Healthcare BV, Huis terHeideweg 62, 3705 LZ Zeist, Netherlands. Further information available from Customer Contact Centre, GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex UB11 1BT.
Trade marks are owned by or licensed to the ViiV Healthcare group of companies.
Date of approval: November 2018. Zinc code: UK/DLG/0055/13(15)
Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or
search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GlaxoSmithKline on
0800 221441.
Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, PharmacovigilanceSection, Health Products Regulatory Authority, Earlsfort Terrace, Dublin 2, Tel: +353 1 676 4971, [email protected]. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.
POM S1A
Prescribing Information
Epivir - Lamivudine 300mg tabletsSee Summary of Product Characteristics (SmPC) before prescribing
Indications: HIV in adults, adolescents and children weighing at least 25 kg as part of combination therapy. Dose: Adults: one 300mg tablet daily with or without food. See SmPC for dosage in children and adolescents. Additional formulations available: 150mg tablets and Oral Solution (10mg/mL) – see SmPCs. Elderly: No specific data. Renal impairment: Creatinine clearance <50ml/min: see SmPC for dosage adjustment. Hepatic impairment: no dose adjustment required. Contraindications: Hypersensitivity to any ingredient. Warnings/precautions: High risk of virologicalfailure (when used in a triple nucleoside regimen), immune reactivation syndrome, osteonecrosis, increased weight, lipids, glucose. Monitor LFTs in Hepatitis B/C co-infection. Use with cladribine, emtricitabine or high doses of co-trimoxazole not recommended. When possible, avoid chronic co-administration of sorbitol or other osmotic acting alcohols (see SmPC section 4.5). If unavoidable, consider more frequent viral load monitoring.
Pregnancy/lactation: Not recommended. Avoid breast-feeding. Side effects: See SmPC for full details. Headache, GI disturbance, insomnia, cough, nasal symptoms, rash, alopecia, arthralgia, muscle disorders, fatigue, malaise, fever, blood dyscrasias, pancreatitis, hepatitis, angioedema, rhabdomyolysis, lactic acidosis, peripheral neuropathy. Transient increases in liver enzymes. Basic NHS costs: 30 tablets: £157.51 EU/1/04/298/002. MA holder: ViiV Healthcare UK Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS. Further information is available from Customer Contact Centre, GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex UB11 1BT.
Trade marks are owned by or licensed to the ViiV Healthcare group of companies.
Date of approval: June 2018. Zinc code: UK/3TC/0001/18
Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or
search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GSK on 0800 221441.
Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, PharmacovigilanceSection, Health Products Regulatory Authority, Earlsfort Terrace, Dublin 2, Tel: +353 1 676 4971, [email protected]. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.
POM S1A