triumeq * (dtg/abc/3tc): bioequivalence data · triumeq® * (dtg/abc/3tc): bioequivalence data...

TRIUMEQ®* (DTG/ABC/3TC):

BIOEQUIVALENCE DATA

UK/TRIM/0048/14(2)

Date of preparation: March2017

Prescribing information is available at the end of this presentation

*In studies supporting TRIUMEQ, DTG 50 mg + ABC 600 mg/3TC 300 mg were used.

Bioequivalence has been demonstrated.

DTG, dolutegravir; ABC, abacavir; 3TC, lamivudine

DECLARATION OF INTEREST

In studies supporting TRIUMEQ, DTG 50 mg + ABC 600 mg/3TC 300 mg were used

Bioequivalence was demonstrated between the TRIUMEQ as a single-pill and the

separate co-administered tablet formulations of DTG + ABC/3TC

INTRODUCTION: TRIUMEQ AND DTG + ABC/3TC –

BIOEQUIVALENCE

TRIUMEQ Summary of Product Characteristics, January 2017; Weller S et al. JAIDS 2014;66:393-8

KEY STUDIES

† DTG 50mg + ABC 600mg/3TC 300mg were

used. Bioequivalence has been

demonstrated.13

* BR - background regimen

** OBR - optimised background regimen

1. Clotet B et al. Lancet. 2014;383(9936):2222-2231. 2. Orrell C et al. Presented at 21st International AIDS Conference, 18th-22nd July, 2016; Durban, South Africa.

Abstract THAB0205LB. 3. Walmsley S et al. N Engl J Med. 2013;369(19):1807-1818. 4. Walmsley S et al. J Acquir Immune Defic Syndr. 2015;70:515-519. 5. Molina

J-M et al. Lancet HIV.2015;2(4):e127-e136. January 2017. 6. Raffi F et al. Lancet Infect Dis. 2013;13:927–935 7. Raffi F et al. Lancet. 2013; 381: 735–743. 8. Cahn P

et al. Lancet. 2013; 382: 700–708. 9. Trottier B et al. Presented at 55th Interscience Conference on Antimicrobial Agents and Chemotherapy, 17th-21st September,

2015; San Diego, CA. LB3271. 10 Lake JE et al. Presented at 21st International AIDS Conference, 18th-22nd July, 2016; Durban, South Africa. Abstract THAB0203.

11. Castagna A et al. J Infect Dis. 2014; 210:354-362.

AT

RIP

LA

®

SINGLE Treatment-naïve patients

TRIUMEQ® † QD vs Atripla® QD (N=833)

SUPERIOR EFFICACY

vs Atripla®

at weeks 48 (primary endpoint),

96 and 144

BO

OS

TE

D P

ls

FLAMINGO Treatment-naïve patients

DTG + 2 NRTIs QD vs DRV/r + 2 NRTIs QD (N=484)

SUPERIOR EFFICACY

vs darunavir/r

at weeks 48 (primary endpoint)

and 96

ARIA Treatment-naïve women

TRIUMEQ QD vs ATV/r + TDF/FTC QD (N=495)

SUPERIOR EFFICACY

vs atazanavir/r

at week 48 (primary endpoint)

INIs

SPRING-2 Treatment-naïve patients

DTG + 2 NRTIs QD vs RAL + 2 NRTIs BID (N=822)

NON-INFERIOR EFFICACY

vs raltegravir

at weeks 48 (primary endpoint) and 96

SAILING Treatment-experienced,

INI-naïve patients

DTG QD + BR* vs RAL BID + BR* (N=719)

SUPERIOR EFFICACY

vs raltegravir

at week 48 (primary endpoint)

Co

nti

nu

ing

AR

T

STRIIVING Treatment-experienced,

stable-switch patients

TRIUMEQ QD vs continuing ARV regimen (N=551)

NON-INFERIOR EFFICACY

up to weeks 24 (primary endpoint)

and 48

Hea

vily

Trea

tmen

t-

Exp

erie

nce

d

VIKING-3

Heavily treatment experienced

patients with RAL and/or EVG

resistant HIV-1

DTG 50mg BD + OBR** (N=183)-single-arm study

SUSTAINED EFFICACY

up to weeks 24 (primary endpoint)

and 48

BIOEQUIVALENCE

FDCs have greatly simplified the treatment of patients with HIV

DTG is a booster-free INI approved for treatment of HIV-1 infection in combination

with other antiretroviral agents

ABC and 3TC are NRTIs available as a single pill (Kivexa®)

The combination of DTG, ABC and 3TC as a single pill would have several potential

advantages over other FDCs, including fewer drug interactions, once daily dosing,

no need for boosting and no time-of-day or food restrictions

DTG, ABC and 3TC as a single pill is suitable for HLA-B*5701-negative patients

TRIUMEQ (DTG/ABC/3TC) SINGLE PILL

REGIMEN BIOEQUIVALENCE: INTRODUCTION

TRIUMEQ Summary of Product Characteristics, January 2017; Kivexa Summary of Product Characteristics, October 2016; Ramjan R et al. Trop Med Int Health

2014;19:501-13; Weller S et al. JAIDS 2014;66:393-8

Primary objective

Evaluate single-dose bioequivalence in the fasted state between the TRIUMEQ

(DTG/ABC/3TC; 50/600/300 mg) single-pill and DTG 50 mg given with separate

ABC/3TC (600/300 mg) to healthy volunteers (Part A)

Secondary objectives

Evaluate the effect of food on the bioavailability of single-dose TRIUMEQ (Part B)

Assess the safety and tolerability of single-dose administration of DTG, ABC and 3TC

in healthy volunteers either fasted or with food

TRIUMEQ SINGLE PILL REGIMEN

BIOEQUIVALENCE: OBJECTIVES

Weller S et al. JAIDS 2014;66:393-8

Single-dose, open-label, randomised, two-period crossover study

Part A: Bioequivalence

Part B: Food effect


BIOEQUIVALENCE: STUDY DESIGN

Pharmacokinetic study of TRIUMEQ vs component exposures and TRIUMEQ food effect

Randomisation

(N=65)

Single-dose

TRIUMEQ FDC

(fasted)

Single-dose

DTG + ABC/3TC

(fasted)

Washout

(≥7 days)

Washout

(≥7 days)

Single-dose

DTG + ABC/3TC

(fasted)

Single-dose

TRIUMEQ FDC

(fasted)

48-hour serial PK sampling 48-hour serial PK sampling

12 patients from

Part A

Single-dose TRIUMEQ

FDC + high-fat meal

Washout

(≥7 days)

48-hour serial PK sampling

Adapted from Weller S et al. JAIDS 2014;66:393-8

7 and 14 day

follow up

7 and 14 day

follow up


BIOEQUIVALENCE: STUDY DESIGN

Point estimates and their associated 90% confidence intervals (CIs) were constructed for the

differences, test treatment (A) – reference treatment (B), for bioequivalence assessment Adapted from Weller S et al. JAIDS 2014;66:393-8

• Serial blood samples were collected up to 48 hours after each treatment for determination of AUC and Cmax

for each of DTG, ABC and 3TC

Plasma parameters such as AUC and Cmax are used to determine the pharmacokinetics (PK) of a drug

There was a ≥7-day washout

period between the second dose

in part A and the dose in part B


BIOEQUIVALENCE: STUDY PROCEDURE


65 subjects randomised to either Group 1 or Group 2

Group 1 received a single dose of Triumeq FDC followed by DTG +

ABC/3TC

Group 2 received DTG + ABC/3TC followed by a single dose of TRIUMEQ

FDC

62 subjects completed the study


BIOEQUIVALENCE: STUDY POPULATION


BIOEQUIVALENCE: PATIENT DEMOGRAPHICS

Demographics

TRIUMEQ

fasted

(n=65)

DTG + ABC/3TC

fasted

(n=65)

TRIUMEQ

fed

(n=12)

Age, mean (SD), years 29.3 (9.59) 29.3 (9.55) 33.8 (11.06)

Sex, n (%)

Female 22 (34%) 22 (34%) 4 (33%)

Male 43 (66%) 43 (66%) 8 (67%)

BMI, mean (SD), kg/m2 25.03 (3.72) 25.16 (3.71) 26.48 (3.09)

Height, mean (SD), cm 172.55 (10.01) 172.58 (9.97) 175.86 (11.64)

Weight, mean (SD), kg 74.69 (13.72) 75.05 (13.48) 82.29 (14.75)

Race, n (%)

African American/African heritage 25 (38%) 25 (38%) 5 (42%)

White – White/Caucasian/European heritage 34 (52%) 34 (52%) 7 (58%)

Part A Part B

BMI, body mass index; SD, standard deviation


Mean plasma concentration–time plots (linear)

TRIUMEQ SINGLE PILL REGIMEN IS

BIOEQUIVALENT TO DTG + ABC/3TC (1)

Adapted from: ViiV Healthcare. Data on File: UK/DLG/0094/14; July 2016

Mean plasma DTG concentration-time Mean plasma ABC concentration-time Mean plasma 3TC concentration-time

Planned relative time (h)

Co

nce

ntr

atio

n (µ

g/m

L)

2.5

2.0

1.5

1.0

0.5

0 24 0 12 36 48

1.5

0.5

2.0

24 0 12 36 48

2.5

1

0

24 0 12 36 48

4

3

2

1

0

Co

nce

ntr

atio

n (µ

g/m

L)

Co

nce

ntr

atio

n (µ

g/m

L)


DTG + ABC/3TC fasted (n=65) TRIUMEQ FDC fasted (n=65)


Geometric mean ratios and 90% confidence intervals for TRIUMEQ single pill

vs DTG + ABC/3TC co-administration (n=65)



Adapted from: Weller S et al. JAIDS 2014;66:393-8

Zone of bioequivalence (0.8–1.25)

0.7 0.8 0.9 1.0 1.1 1.2 1.3

Dolutegravir

AUC0-

Cmax

AUC0-

Cmax

AUC0-

Cmax

Abacavir

Lamivudine

Bioequivalence was shown for all

3 TRIUMEQ components in the

single-pill formulation vs separate

administration of DTG and ABC/3TC

AUC, area under the curve; Cmax, maximum observed plasma concentration

90% confidence intervals for the geometric mean ratios of key exposure parameters between the FDC and

the separate tablets fell within the standard 0.8–1.25 range for all 3 components, confirming bioequivalence




Study part A: summary and statistical comparison of selected PK parameters for BE assessment

FDC fasted GLS

mean

(n=62)

DTG + ABC/3TC

fasted GLS mean

(n=62)

Ratio of GLS mean

(90% CI)

DTG PK parameters

AUC0–, µg·h/mL 44.73 47.36 0.945 [0.889, 1.00]

AUC0–t, µg·h/mL 40.86 43.34 0.943 [0.888, 1.00]

Cmax, µg/mL 2.44 2.54 0.961 [0.906, 1.02]

ABC PK parameters

AUC0–, µg·h/mL 13.92 14.51 0.960 [0.939, 0.980]

AUC0–t, µg·h/mL 13.90 14.48 0.960 [0.939, 0.980]

Cmax, µg/mL 4.03 4.38 0.920 [0.867, 0.977]

3TC PK parameters

AUC0–, µg·h/mL 12.75 13.12 0.972 [0.940, 1.01]

AUC0–t, µg·h/mL 12.30 12.81 0.960 [0.928, 0.994]

Cmax, µg/mL 2.11 2.28 0.926 [0.885, 0.968]

CI, confidence interval; GLS, geometric least squares; PK, pharmacokinetic

CHANGES IN DTG, ABC AND 3TC EXPOSURE

AND Cmax WITH FOOD

Study part B: statistical comparison of selected PK parameters for food effect assessment

Ratio of GLS mean [90% CI]

TRIUMEQ fed vs TRIUMEQ fasted

DTG PK parameters

AUC0– 1.48 [1.36, 1.62]

AUC0–t 1.47 [1.35, 1.60]

Cmax 1.37 [1.26, 1.48]

ABC PK parameters

AUC0– 0.926 [0.899, 0.953]

AUC0–t 0.924 [0.898, 0.952]

Cmax 0.774 [0.662, 0.905]

3TC PK parameters

AUC0– 1.04 [0.971, 1.12]

AUC0–t 1.05 [0.963, 1.14]

Cmax 0.960 [0.879, 1.05]


DTG plasma exposures with a high-fat meal

Approximately 48% higher for AUC and 37% higher for Cmax than in the fasted condition

Indicate that TRIUMEQ can be taken with or without food

ABC and 3TC plasma exposures with a high-fat meal

Generally similar to fasted exposures

Cmax for ABC was 23% lower with food

Consistent with prior results for ABC/3TC, which may be taken with or without food

TRIUMEQ AND FOOD

Weller S et al. JAIDS 2014;66:393-8; TRIUMEQ Summary of Product Characteristics, January 2017

Study Part A Only (no events for Part B)


BIOEQUIVALENCE:

SUMMARY OF DRUG-RELATED AEs

Preferred term TRIUMEQ fasted

(n=65)

DTG + ABC/3TC fasted

(n=65)

Patients with any drug-related AE, n (%) 12 (18%) 18 (28%)

Nausea 10 (15%) 18 (28%)

Headache 2 (3%) 4 (6%)

Abdominal pain 0 1 (2%)

Vomiting 1 (2%) 0

Dizziness 1 (2%) 0

Feeling hot 0 1 (2%)


Bioequivalence was demonstrated between TRIUMEQ as a single pill and the

separate co-administered tablet formulations of DTG + ABC/3TC

TRIUMEQ may be taken with or without food

Tolerability results (single-dose, healthy volunteers)

Part A: numerically fewer drug-related AEs with TRIUMEQ compared with separate

DTG + ABC/3TC (18% vs 28%, respectively)

Part B: no adverse events were reported


BIOEQUIVALENCE: CONCLUSIONS

Weller S et al. JAIDS 2014;66:393-8; TRIUMEQ Summary of Product Characteristics. January 2017

TRIUMEQ is indicated for the treatment of HIV-infected adults and adolescents who:

are above 12 years of age, and

weigh at least 40 kg

TRIUMEQ is not recommended for use in patients with:

HLA-B*5701 allele

a creatinine clearance below 50 ml/min, or

moderate or severe hepatic impairment

TRIUMEQ is contraindicated:

in patients with hypersensitivity to dolutegravir, abacavir, lamivudine or to any of the

tablet excipients

for use with dofetilide* co-administration

TRIUMEQ INDICATION

TRIUMEQ Summary of Product Characteristics, January 2017

*Dofetilide is not licensed in the UK or Ireland

HLA / HYPERSENSITIVITY CONSIDERATIONS

Hypersensitivity reactions have been observed more commonly with abacavir, some of

which have been life-threatening, and in rare cases fatal, when not managed

appropriately. The risk for abacavir HSR to occur is high for patients who test positive for

the HLA‐B*5701 allele. However, abacavir HSRs have been reported at a low frequency

in patients who do not carry this allele.

Before initiating treatment with TRIUMEQ▼, screening for carriage of the HLA-B*5701

allele should be performed in any HIV-infected patient, irrespective of racial origin

TRIUMEQ should never be initiated in patients with a positive HLA-B*5701 status, nor in

patients with a negative HLA-B*5701 status who had a suspected abacavir HSR on a

previous abacavir-containing regimen


TRIUMEQ▼: SPECIAL WARNINGS AND

PRECAUTIONS FOR USE

Liver disease

Patients with chronic hepatitis B or C

Immune Reactivation Syndrome

Mitochondrial dysfunction

Myocardial infarction

Weight and metabolic parameters

Osteonecrosis

Opportunistic infections

Drug resistance

Drug interactions


3TC, lamivudine

ABC, abacavir

AE, adverse event

AUC, area under the curve

BE, bioequivalence

BID, twice daily

BMI, body mass index

CI, confidence interval

CL/F, Apparent total clearance of the drug

from plasma after oral administration

Cmax, maximum observed plasma

concentration

CNS, central nervous system

DRV, darunavir

DRV/r, darunavir/ritonavir

ABBREVIATIONS

DTG, dolutegravir

EFV, efavirenz

EVG, elvitegravir

FDC, fixed-dose combination

FTC, emtricitabine

GLS, geometric least squares

HIV, human immunodeficiency virus

INI, integrase inhibitor

NRTI, nucleoside reverse transcriptase inhibitor

PK, pharmacokinetic

QD, once daily

RAL, raltegravir

SD, standard deviation

TDF, tenofovir disoproxil fumarate

PRESCRIBING INFORMATION TRIUMEQ® ▼ (DOLUTEGRAVIR 50MG/ABACAVIR 600MG/LAMIVUDINE 300MG TABLETS)

(SEE SUMMARY OF PRODUCT CHARACTERISTICS BEFORE PRESCRIBING)

Indication: HIV in over 12 years and > 40kg. Screen for HLA-B*5701

prior to use. Do not use if HLA-B*5701 positive. Dose: one tablet once

daily with or without food. Elderly: Limited data in 65+ yrs. Creatinine

clearance <50ml/min or moderate/severe hepatic impairment: Not

recommended. Monitor closely in mild hepatic impairment.

Contraindications: Hypersensitivity to any ingredient. Co-administration

with dofetilide. Warnings/precautions: Both abacavir and dolutegravir

are associated with risk of hypersensitivity reactions (HSR). Do not

initiate in HLA-B*5701+ or previous suspected abacavir HSR. Stop

Triumeq without delay if HSR suspected. Never reintroduce any

dolutegravir- or abacavir-containing product after suspected HSR. Risks

of immune reactivation syndrome, osteonecrosis, increased weight,

lipids, glucose. Monitor LFTs in Hepatitis B/C co-infection. Inconclusive

data on relationship between abacavir and MI; minimise all modifiable CV

risk factors (e.g. smoking, hypertension, hyperlipidaemia). Not

recommended if dolutegravir required b.d. (with etravirine [without

boosted PI], efavirenz, nevirapine, rifampicin, boosted tipranavir,

carbamazepine, oxcarbazepine, phenytoin, phenobarbital and St John’s

Wort). Use with cladribine not recommended. Use

with Mg/Al-containing antacids, calcium, multivitamins or iron requires

dosage separation. Caution with metformin: monitor renal function and

consider metformin dose adjustment. Pregnancy/lactation: Not

recommended. Avoid breast-feeding. Side effects: See SPC for details.

Headache, insomnia, sleep/dream disorders, GI disturbance, fatigue,

hypersensitivity, anorexia, depression, dizziness, somnolence, lethargy,

malaise, cough, nasal symptoms, rash, pruritus, alopecia, arthralgia,

myalgia, asthenia, fever, elevations of ALT, AST and CPK, blood

dyscrasias, suicidal ideation or suicide attempt, rhabdomyolysis, lactic

acidosis, erythema multiforme, Stevens-Johnson syndrome, toxic

epidermal necrolysis. Basic NHS costs: 30 tablets: £798.16

EU/1/14/940/001. 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.

S1A

Triumeq is a registered trademark of the ViiV Healthcare Group of

Companies.

Date of approval: January 2017 Zinc code: UK/TRIM/0037/14(7)

POM

Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should

also be reported to GlaxoSmithKline on 0800 221 441.

Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, Pharmacovigilance Section, 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.

http://www.mhra.gov.uk/yellowcard

mailto:[email protected]

PRESCRIBING INFORMATION TIVICAY® ▼ (DOLUTEGRAVIR 50MG TABLETS)


Indication: HIV in >12 years and >40kg as part of combination

therapy. Dosing: 50mg once daily with or without food if no proven/

suspected integrase resistance. 50mg twice daily with efavirenz,

nevirapine, tipranavir/ritonavir, etravirine (without boosted PI),

carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John’s

Wort or rifampicin. Adults with proven/ suspected integrase resistance:

50mg twice daily preferably with food. 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. 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 SPC for full details. Headache, GI disturbance, insomnia,

abnormal dreams, depression, dizziness, rash, pruritus, fatigue,

elevations of ALT, AST and CPK, arthralgia, myalgia, hypersensitivity,

suicidal ideation or suicide attempt. Basic NHS costs: 30 tablets

£498.75 EU/1/13/892/001. MA holder: ViiV Healthcare UK Ltd, 980

Great West Road, Brentford, Middlesex TW8 9GS. Further information

available from Customer Contact Centre, GlaxoSmithKline UK Ltd,

Stockley Park West, Uxbridge, Middlesex UB11 1BT.

Tivicay is a registered trademark of the ViiV Healthcare Group of

Companies

Date of approval: January 2017. Zinc code: UK/DLG/0055/13(9)

POM

Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events

should also be reported to GlaxoSmithKline on 0800 221 441.

Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, Pharmacovigilance Section,

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.

S1A



PRESCRIBING INFORMATION

KIVEXA ® (ABACAVIR 600MG/LAMIVUDINE 300MG TABLETS)


Indications: HIV in adults, adolescents and children weighing at

least 25 kg as part of combination therapy. Screen for HLA-

B*5701 prior to use. Dose: one tablet daily with or without food.

Elderly: No pharmacokinetic data in 65+ yrs. Renal impairment:

Creatinine clearance <50ml/min: not recommended. Hepatic

impairment: not recommended in moderate or severe hepatic

impairment. Monitor closely in mild hepatic impairment.

Contraindications: Hypersensitivity to any ingredient.

Warnings/precautions: Risk of hypersensitivity reactions (HSR).

Do not initiate in HLA-B*5701+ or previous suspected abacavir

HSR. Stop Kivexa without delay if HSR suspected. Never re-

introduce any abacavir-containing product after suspected HSR.

Risks of virological failure, immune reactivation syndrome,

osteonecrosis, increased weight, lipids, glucose. Monitor LFTs in

Hepatitis B/C co-infection. Inconclusive data on relationship

between abacavir and MI; minimise modifiable CV risk factors

(e.g. smoking, hypertension, hyperlipidaemia). Use with cladribine,

emtricitabine or high doses of co-trimoxazole

not recommended. Pregnancy/lactation: Not recommended. Avoid

breast-feeding. Side effects: See SPC for full details.

Hypersensitivity, GI disturbance, headache, anorexia, insomnia,

rash, fever, lethargy, fatigue, malaise, arthralgia, muscle disorders,

nasal symptoms, cough, alopecia, blood dyscrasias,

rhabdomyolysis, lactic acidosis, erythema multiforme, Stevens-

Johnson syndrome and toxic epidermal necrolysis. Basic NHS

costs: 30 tablets: £299.41 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.

Kivexa is a registered trademark of the ViiV Healthcare Group of

Companies

Date of approval: October 2016 Zinc code: UK/ABC3TC/0008/13(9)

POM

Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events

should also be reported to GlaxoSmithKline on 0800 221 441.

Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, Pharmacovigilance Section,

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.

S1A



triumeq * (dtg/abc/3tc): bioequivalence data · triumeq® * (dtg/abc/3tc): bioequivalence data...

Documents