Celsentri

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ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 



 
 
 

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1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 25 mg film-coated tablets 
CELSENTRI 75 mg film-coated tablets 
CELSENTRI 150 mg film-coated tablets 
CELSENTRI 300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
CELSENTRI 25 mg film-coated tablets 
 
Each film-coated tablet contains 25 mg of maraviroc. 
Excipient with known effect: each 25 mg film-coated tablet contains 0.14 mg of soya lecithin. 
 
CELSENTRI 75 mg film-coated tablets  
 
Each film-coated tablet contains 75 mg of maraviroc.  
Excipient with known effect: each 75 mg film-coated tablet contains 0.42 mg of soya lecithin. 
 
CELSENTRI 150 mg film-coated tablets 
 
Each film-coated tablet contains 150 mg of maraviroc.  
Excipient with known effect: each 150 mg film-coated tablet contains 0.84 mg of soya lecithin. 
 
CELSENTRI 300 mg film-coated tablets 
 
Each film-coated tablet contains 300 mg of maraviroc. 
Excipient with known effect: each 300 mg film-coated tablet contains 1.68 mg of soya lecithin.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet.  
 
CELSENTRI 25 mg film-coated tablets 
 
Blue, biconvex, oval film-coated tablets, approximate dimensions 4.6 mm x 8.0 mm and debossed 
with “MVC 25”. 
 
CELSENTRI 75 mg film-coated tablets 
 
Blue, biconvex, oval film-coated tablets, approximate dimensions 6.74 mm x 12.2 mm and 
debossed with “MVC 75”. 
 
CELSENTRI 150 mg film-coated tablets 
 
Blue, biconvex, oval film-coated tablets, approximate dimensions 8.56 mm x 15.5 mm and 
debossed with “MVC 150”. 
 
CELSENTRI 300 mg film-coated tablets 
 
Blue, biconvex, oval film-coated tablets, approximate dimensions 10.5 mm x 19.0 mm and 
debossed with “MVC 300”. 



 
 
 

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4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
CELSENTRI, in combination with other antiretroviral medicinal products, is indicated for 
treatment-experienced adults, adolescents and children of 2 years of age, and older and weighing at 
least 10 kg infected with only CCR5-tropic HIV-1 detectable (see sections 4.2 and 5.1). 
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
Before taking CELSENTRI it has to be confirmed that only CCR5-tropic HIV-1 is detectable (i.e. 
CXCR4 or dual/mixed tropic virus not detected) using an adequately validated and sensitive 
detection method on a newly drawn blood sample. The Monogram Trofile assay was used in the 
clinical studies of CELSENTRI (see sections 4.4 and 5.1). The viral tropism cannot be safely 
predicted by treatment history and assessment of stored samples. 
 
There are currently no data regarding the reuse of CELSENTRI in patients that currently have only 
CCR5-tropic HIV-1 detectable, but have a history of failure on CELSENTRI (or other CCR5 
antagonists) with a CXCR4 or dual/mixed tropic virus. There are no data regarding the switch from 
a medicinal product of a different antiretroviral class to CELSENTRI in virologically suppressed 
patients. Alternative treatment options should be considered.   
 
Adults 
The recommended dose of CELSENTRI is 150 mg (with potent CYP3A inhibitor with or without a 
potent CYP3A inducer), 300 mg (without potent CYP3A inhibitors or inducers) or 600 mg twice 
daily (with potent CYP3A inducer without a potent CYP3A inhibitor) depending on interactions 
with concomitant antiretroviral therapy and other medicinal products (see section 4.5).  
 
Children from 2 years of age and weighing at least 10kg 
The recommended dose of CELSENTRI should be based on body weight (kg) and should not 
exceed the recommended adult dose. If a child is unable to reliably swallow CELSENTRI tablets, 
the oral solution (20 mg per mL) should be prescribed (refer to Summary of Product Characteristics 
for CELSENTRI oral solution). 
 
The recommended dose of CELSENTRI differs depending on interactions with concomitant 
antiretroviral therapy and other medicinal products. Refer to section 4.5 for corresponding adult 
dosage.  
 
Many medicines have profound effects on maraviroc exposure due to drug-drug interactions. Prior 
to deciding the dose of CELSENTRI by weight, please refer to Table 2 in section 4.5 to carefully 
determine the corresponding adult dose. The corresponding paediatric dose can then be obtained 
from Table 1 below. If uncertainty still exists, contact a pharmacist for advice. 
 



 
 
 

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Table 1 Recommended dosing regimen in children aged 2 years and above and weighing at 
least 10 kg 
 

Adult 
dosage* 

Concomitant 
Medications 

Dose of CELSENTRI in children based on weight 

10 to 
less than 20 kg 

20 to 
less than 

30 kg 

30 to 
less than  

40 kg 

at least 
40 kg 

150 mg twice 
daily 

CELSENTRI 
with products 
that are potent 
CYP3A 
inhibitors (with 
or without a 
CYP3A inducer) 

50 mg 
twice daily 

75 mg 
twice daily 

100 mg 
twice daily 

150 mg 
twice daily 

300 mg twice 
daily 

CELSENTRI 
with products 
that are not 
potent CYP3A 
inhibitors or 
potent CYP3A 
inducers 

 
 Data to support these doses are 

lacking. 

300 mg 
twice daily 

300 mg 
twice daily 

600 mg twice 
daily 

CELSENTRI 
with products 
that are CYP3A 
inducers (without 
a potent CYP3A 
inhibitor) 

Data to support these doses are lacking and CELSENTRI is not 
recommended in children taking concomitant interacting 
medicinal products that in adults would require a 600 mg twice 
daily dose. 

 

* Based on drug-drug Interactions (refer to section 4.5) 
 
Special populations 
 
Elderly  
There is limited experience in patients >65 years of age (see section 5.2), therefore CELSENTRI 
should be used with caution in this population. 
 
Renal impairment  
In adult patients with a creatinine clearance of <80 mL/min, who are also receiving potent CYP3A4 
inhibitors, the dose interval of maraviroc should be adjusted to 150 mg once daily (see sections 4.4 
and 4.5).   
 
Examples of agents/regimens with such potent CYP3A4-inhibiting activity are: 
 

• ritonavir-boosted protease inhibitors (with the exception of tipranavir/ritonavir),  
• cobicistat,  
• itraconazole, voriconazole, clarithromycin and telithromycin, 
• telaprevir and boceprevir. 

 
CELSENTRI should be used with caution in adult patients with severe renal impairment  
(CLcr <30 mL/min) who are receiving potent CYP3A4 inhibitors (see sections 4.4 and 5.2). 
 
There are no data available to recommend a specific dose in paediatric patients with renal 
impairment. Therefore, CELSENTRI should be used with caution in this population. 
 



 
 
 

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Hepatic impairment  
Limited data are available in adult patients with hepatic impairment and no data are available to 
recommend a specific dose for paediatric patients.  Therefore, CELSENTRI should be used with 
caution in patients with hepatic impairment (see sections 4.4 and 5.2).  
 
Paediatric patients (children younger than 2 years of age or weighing less than 10 kg) 
The safety and efficacy of CELSENTRI in children younger than 2 years of age or weighing less 
than 10 kg has not been established (see section 5.2). No data are available.  
 
Method of administration 
 
Oral use. 
CELSENTRI can be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to peanut or soya or to any of the excipients listed in 
section 6.1. 
 
4.4 Special warnings and precautions for use 
 
General 
 
While effective viral suppression with antiretroviral therapy has been proven to substantially 
reduce the risk of sexual transmission, a residual risk cannot be excluded.  Precautions to prevent 
transmission should be taken in accordance with national guidelines. 
 
Hepatic disease  
 
The safety and efficacy of maraviroc have not been specifically studied in patients with significant 
underlying liver disorders.  
 
Cases of hepatotoxicity and hepatic failure with allergic features have been reported in association 
with maraviroc. In addition, an increase in hepatic adverse reactions with maraviroc was observed 
during studies of treatment-experienced subjects with HIV infection, although there was no overall 
increase in ACTG Grade 3/4 liver function test abnormalities (see section 4.8). Hepatobiliary 
disorders reported in treatment-naïve patients were uncommon and balanced between treatment 
groups (see section 4.8). Patients with pre-existing liver dysfunction, including chronic active 
hepatitis, can have an increased frequency of liver function abnormalities during combination 
antiretroviral therapy and should be monitored according to standard practice. 
 
Discontinuation of maraviroc should be strongly considered in any patient with signs or symptoms 
of acute hepatitis, in particular if drug-related hypersensitivity is suspected or with increased liver 
transaminases combined with rash or other systemic symptoms of potential hypersensitivity (e.g. 
pruritic rash, eosinophilia or elevated IgE). 
 
There are limited data in patients with hepatitis B and/or C virus co-infection (see section 5.1). 
Caution should be exercised when treating these patients. In case of concomitant antiviral therapy 
for hepatitis B and/or C, please refer to the relevant product information for these medicinal 
products. 
 
There is limited experience in patients with reduced hepatic function, therefore maraviroc should 
be used with caution in this population (see sections 4.2 and 5.2). 
 



 
 
 

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Severe skin and hypersensitivity reactions 
 
Hypersensitivity reactions including severe and potentially life threatening events have been 
reported in patients taking maraviroc, in most cases concomitantly with other medicinal products 
associated with these reactions. These reactions included rash, fever, and sometimes organ 
dysfunction and hepatic failure. Discontinue maraviroc and other suspect agents immediately if 
signs or symptoms of severe skin or hypersensitivity reactions develop. Clinical status and relevant 
blood chemistry should be monitored and appropriate symptomatic therapy initiated. 
 
Cardiovascular safety 
 
Limited data exist with the use of maraviroc in patients with severe cardiovascular disease, 
therefore special caution should be exercised when treating these patients with maraviroc. In the 
pivotal studies of treatment-experienced patients coronary heart disease events were more common 
in patients treated with maraviroc than with placebo (11 during 609 PY vs 0 during 111 PY of 
follow-up). In treatment-naïve patients such events occurred at a similarly low rate with maraviroc 
and control (efavirenz). 
 
Postural hypotension 
 
When maraviroc was administered in studies with healthy volunteers at doses higher than the 
recommended dose, cases of symptomatic postural hypotension were seen at a greater frequency 
than with placebo.   Caution should be used when administering maraviroc in patients on 
concomitant medicinal products known to lower blood pressure.  Maraviroc should also be used 
with caution in patients with severe renal insufficiency and in patients who have risk factors for, or 
have a history of postural hypotension.  Patients with cardiovascular co-morbidities could be at 
increased risk of cardiovascular adverse reactions triggered by postural hypotension. 
 
Renal impairment 
 
An increased risk of postural hypotension may occur in patients with severe renal insufficiency 
who are treated with potent CYP3A inhibitors or boosted protease inhibitors (PIs) and maraviroc. 
This risk is due to potential increases in maraviroc maximum concentrations when maraviroc is 
co-administered with potent CYP3A inhibitors or boosted PIs in these patients.  
 
Immune reconstitution syndrome 
 
In HIV infected patients with severe immune deficiency at the time of institution of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of CART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, 
and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii). Any 
inflammatory symptoms should be evaluated and treatment initiated when necessary. Autoimmune 
disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in 
the setting of immune reactivation; however, the reported time to onset is more variable and these 
events can occur many months after initiation of treatment. 
 
Tropism 
 
 
Maraviroc should only be used when only CCR5-tropic HIV-1 is detectable (i.e. CXCR4 or 
dual/mixed tropic virus not detected) as determined by an adequately validated and sensitive 
detection method (see sections 4.1, 4.2 and 5.1). The Monogram Trofile assay was used in the 
clinical studies of maraviroc. The viral tropism cannot be predicted by treatment history or 
assessment of stored samples.  



 
 
 

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Changes in viral tropism occur over time in HIV-1 infected patients. Therefore there is a need to 
start therapy shortly after a tropism test. 
 
Background resistance to other classes of antiretrovirals have been shown to be similar in previously 
undetected CXCR4-tropic virus of the minor viral population, as that found in CCR5-tropic virus. 
 
Maraviroc is not recommended to be used in treatment-naïve patients based on the results of a 
clinical study in this population (see section 5.1). 
 
Dose adjustment 
 
Physicians should ensure that appropriate dose adjustment of maraviroc is made when maraviroc is 
co-administered with potent CYP3A4 inhibitors and/or inducers since maraviroc concentrations 
and its therapeutic effects may be affected (see sections 4.2 and 4.5). Please also refer to the 
respective Summary of Product Characteristics of the other antiretroviral medicinal products used 
in the combination.  
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have 
been reported particularly in patients with advanced HIV-disease and/or long-term exposure to 
combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if 
they experience joint aches and pain, joint stiffness or difficulty in movement. 
 
Potential effect on immunity 
 
CCR5 antagonists could potentially impair the immune response to certain infections. This should 
be taken into consideration when treating infections such as active tuberculosis and invasive fungal 
infections. The incidence of AIDS-defining infections was similar between maraviroc and placebo 
arms in the pivotal studies.  
 
Soya lecithin 
 
CELSENTRI contains soya lecithin.  
If a patient is hypersensitive to peanut or soya, CELSENTRI should not be used. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Maraviroc is metabolised by cytochrome P450 CYP3A4 and CYP3A5. Co-administration of 
maraviroc with medicinal products that induce CYP3A4 may decrease maraviroc concentrations 
and reduce its therapeutic effects. Co-administration of maraviroc with medicinal products that 
inhibit CYP3A4 may increase maraviroc plasma concentrations. Dose adjustment of maraviroc is 
recommended when maraviroc is co-administered with potent CYP3A4 inhibitors and/or inducers. 
Further details for concomitantly administered medicinal products are provided below (see Table 
2).  
 
Maraviroc is a substrate for the transporters P-glycoprotein and OATP1B1, but the effect of these 
transporters on the exposure to maraviroc is not known. 
 
Based on the in vitro and clinical data, the potential for maraviroc to affect the pharmacokinetics of 
co-administered medicinal products is low.  In vitro studies have shown that maraviroc does not 
inhibit OATP1B1, MRP2 or any of the major P450 enzymes at clinically relevant concentrations 
(CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4). Maraviroc had no 
clinically relevant effect on the pharmacokinetics of midazolam, the oral contraceptives 



 
 
 

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ethinylestradiol and levonorgestrel, or urinary 6β-hydroxycortisol/cortisol ratio, suggesting no 
inhibition or induction of CYP3A4 in vivo. At higher exposure of maraviroc a potential inhibition 
of CYP2D6 cannot be excluded.  
 
Renal clearance accounts for approximately 23% of total clearance of maraviroc when maraviroc is 
administered without CYP3A4 inhibitors. In vitro studies have shown that maraviroc does not 
inhibit any of the major renal uptake transporters at clinically relevant concentrations (OAT1, 
OAT3, OCT2, OCTN1, and OCTN2). Additionally, co-administration of maraviroc with tenofovir 
(substrate for renal elimination) and cotrimoxazole (contains trimethoprim, a renal cation transport 
inhibitor), showed no effect on the pharmacokinetics of maraviroc. In addition, co-administration 
of maraviroc with lamivudine/zidovudine showed no effect of maraviroc on lamivudine (primarily 
renally cleared) or zidovudine (non-P450 metabolism and renal clearance) pharmacokinetics.  
Maraviroc inhibits P-glycoprotein in vitro (IC50 is 183 μM). However, maraviroc does not 
significantly affect the pharmacokinetics of digoxin in vivo.  It may not be excluded that maraviroc 
can increase the exposure to the P-glycoprotein substrate dabigatran etexilate. 
 
Table 2: Interactions and adulta dose recommendations with other medicinal products 
 

Medicinal product by 
therapeutic areas 
(dose of CELSENTRI 
used in study) 

Effects on active substance levels 
Geometric mean change if not 
stated otherwise 

Recommendations 
concerning co-
administration in adults 

ANTI-INFECTIVES   
Antiretrovirals   
Pharmacokinetic Enhancers 
Cobicistat Interaction not studied. 

 
Cobicistat is a potent CYP3A 
inhibitor. 

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when co-
administered with 
cobicistat containing 
regimen. 

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) 
Lamivudine 150 mg BID 
(maraviroc 300 mg BID) 

Lamivudine AUC12: ↔ 1.13  
Lamivudine Cmax: ↔ 1.16  
Maraviroc concentrations not 
measured, no effect is expected. 

No significant interaction 
seen/expected. 
CELSENTRI 300 mg 
twice daily and NRTIs can 
be co-administered 
without dose adjustment. 

Tenofovir 300 mg QD 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↔ 1.03  
Maraviroc Cmax: ↔ 1.03  
Tenofovir concentrations not 
measured, no effect is expected. 

Zidovudine 300 mg BID 
(maraviroc 300 mg BID) 

Zidovudine AUC12: ↔ 0.98  
Zidovudine Cmax: ↔ 0.92  
Maraviroc concentrations not 
measured, no effect is expected. 

Integrase Inhibitors   



 
 
 

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Elvitegravir/ritonavir 
150/100mg QD 
(maraviroc 150 mg BID) 

Maraviroc AUC12: ↑ 2.86 (2.33-3.51) 
Maraviroc Cmax: ↑ 2.15 (1.71-2.69) 
Maraviroc C12: ↑ 4.23 (3.47-5.16) 
 
Elvitegravir AUC24: ↔ 1.07 
(0.96-1.18) 
Elvitegravir Cmax: ↔ 1.01 
(0.89-1.15) 
Elvitegravir C24: ↔ 1.09 (0.95-1.26) 
 

Elvitegravir as a single 
agent is indicated only in 
combination with certain 
ritonavir boosted PIs.  
 
Elvitegravir per se is not 
expected to affect 
maraviroc exposure to a 
clinically relevant degree 
and the observed effect is 
attributed to ritonavir.  
 
Thus, CELSENTRI dose 
should be modified in line 
with the recommendation 
for co-administration with 
respective PI/ritonavir 
combination (see 
‘Protease Inhibitors’). 

Raltegravir 400 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↓ 0.86 
Maraviroc Cmax: ↓ 0.79 
 
Raltegravir AUC12: ↓ 0.63  
Raltegravir Cmax: ↓ 0.67  
Raltegravir C12: ↓ 0.72 
 

No clinically significant 
interaction seen. 
CELSENTRI 300 mg 
twice daily and raltegravir 
can be co-administered 
without dose adjustment. 

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 
Efavirenz 600 mg QD 
(maraviroc 100 mg BID) 

Maraviroc AUC12: ↓ 0.55  
Maraviroc Cmax: ↓ 0.49 
Efavirenz concentrations not 
measured, no effect is expected. 

CELSENTRI dose should 
be increased to 600 mg 
twice daily when 
co-administered with 
efavirenz in the absence of 
a potent CYP3A4 
inhibitor. For combination 
with efavirenz + PI, see 
separate recommendations 
below. 

Etravirine 200 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↓ 0.47  
Maraviroc Cmax: ↓ 0.40  
 
Etravirine AUC12: ↔ 1.06 
Etravirine Cmax: ↔ 1.05 
Etravirine C12: ↔ 1.08 

Etravirine is only 
approved for use with 
boosted protease 
inhibitors. For 
combination with 
etravirine + PI, see below. 

Nevirapine 200 mg BID 
(maraviroc 300 mg Single 
Dose) 

Maraviroc AUC12: ↔ compared to 
historical controls 
Maraviroc Cmax: ↑ compared to 
historical controls 
Nevirapine concentrations not 
measured, no effect is expected. 

Comparison to exposure 
in historical controls 
suggests that 
CELSENTRI 300 mg 
twice daily and nevirapine 
can be co-administered 
without dose adjustment.  

Protease Inhibitors (PIs) 
Atazanavir 400 mg QD 
(maraviroc 300 mg BID) 

Maraviroc AUC12 ↑ 3.57  
Maraviroc Cmax: ↑ 2.09  
Atazanavir concentrations not 
measured, no effect is expected. 

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when 
co-administered with a PI; 



 
 
 

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Atazanavir/ritonavir 
300 mg/100 mg QD 
(maraviroc 300 mg BID) 

Maraviroc AUC12 ↑ 4.88 
Maraviroc Cmax: ↑ 2.67  
Atazanavir/ritonavir concentrations 
not measured, no effect is expected. 

except in combination with 
tipranavir/ritonavir where 
the CELSENTRI dose 
should be 300 mg BID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Lopinavir/ritonavir 
400 mg/100 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12 ↑ 3.95  
Maraviroc Cmax: ↑ 1.97 
Lopinavir/ritonavir concentrations 
not measured, no effect is expected. 

Saquinavir/ritonavir 
1000 mg/100 mg BID 
(maraviroc 100 mg BID) 

Maraviroc AUC12 ↑ 9.77 
Maraviroc Cmax: ↑ 4.78  
Saquinavir/ritonavir concentrations 
not measured, no effect is expected. 

Darunavir/ritonavir 
600 mg/100 mg BID 
(maraviroc 150 mg BID) 

Maraviroc AUC12 ↑ 4.05 
Maraviroc Cmax: ↑ 2.29  
Darunavir/ritonavir concentrations 
were consistent with historical data. 

Nelfinavir 
 

Limited data are available for co-
administration with nelfinavir. 
Nelfinavir is a potent CYP3A4 
inhibitor and would be expected to 
increase maraviroc concentrations. 

Indinavir 
 

Limited data are available for co-
administration with indinavir. 
Indinavir is a potent CYP3A4 
inhibitor. Population PK analysis in 
phase 3 studies suggests dose 
reduction of maraviroc when 
co-administered with indinavir gives 
appropriate maraviroc exposure. 

Tipranavir/ritonavir 
500 mg/200 mg BID 
(maraviroc 150 mg BID) 
 
 
 
 
 
 
 
 
 
 

Maraviroc AUC12 ↔ 1.02  
Maraviroc Cmax: ↔ 0.86  
Tipranavir/ritonavir concentrations 
were consistent with historical data. 



 
 
 

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Fosamprenavir/ritonavir 
700 mg/100 mg BID 
(maraviroc 300 mg BID) 
 
 
 
 
 
 
 
 
 
 

Maraviroc AUC12: ↑ 2.49  
Maraviroc Cmax: ↑ 1.52  
Maraviroc C12: ↑ 4.74  
 
Amprenavir AUC12: ↓ 0.65  
Amprenavir Cmax: ↓ 0.66  
Amprenavir C12: ↓ 0.64  
 
Ritonavir AUC12: ↓ 0.66  
Ritonavir Cmax: ↓ 0.61  
Ritonavir C12: ↔ 0.86  
 
 

Concomitant use is not 
recommended. Significant 
reductions in amprenavir 
Cmin observed may result 
in virological failure in 
patients 
 
 

NNRTI + PI   
Efavirenz 600 mg QD + 
lopinavir/ritonavir 
400mg/100 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↑ 2.53 
Maraviroc Cmax: ↑ 1.25  
Efavirenz, lopinavir/ritonavir 
concentrations not measured, no 
effect expected. 

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when 
co-administered with 
efavirenz and a PI (except 
tipranavir/ritonavir where 
the dose should be 600 mg 
twice daily). 
 
Concomitant use of 
CELSENTRI and 
fosamprenavir/ritonavir is 
not recommended. 

Efavirenz 600 mg QD + 
saquinavir/ritonavir 
1000 mg/100 mg BID 
(maraviroc 100 mg BID) 

Maraviroc AUC12: ↑ 5.00  
Maraviroc Cmax: ↑ 2.26 
Efavirenz, saquinavir/ritonavir 
concentrations not measured, no 
effect expected. 

Efavirenz and 
atazanavir/ritonavir or 
darunavir/ritonavir 

Not studied. Based on the extent of 
inhibition by atazanavir/ritonavir or 
darunavir/ritonavir in the absence of 
efavirenz, an increased exposure is 
expected.  

Etravirine and 
darunavir/ritonavir 
(maraviroc 150 mg BID) 
 
 
 
 
 
 
 
 
 
 
 

Maraviroc AUC12: ↑ 3.10  
Maraviroc Cmax: ↑ 1.77  
 
Etravirine AUC12: ↔ 1.00 
Etravirine Cmax: ↔ 1.08  
Etravirine C12: ↓ 0.81  
 
Darunavir AUC12: ↓ 0.86  
Darunavir Cmax: ↔ 0.96  
Darunavir C12: ↓ 0.77  
 
Ritonavir AUC12: ↔ 0.93 
Ritonavir Cmax: ↔ 1.02 
Ritonavir C12: ↓ 0.74  

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when 
co-administered with 
etravirine and a PI. 
 
Concomitant use of 
CELSENTRI and 
fosamprenavir/ritonavir is 
not recommended. 
 
 
 
 
 
 
 
 
 
 

Etravirine and 
lopinavir/ritonavir, 
saquinavir/ritonavir or 
atazanavir/ritonavir 

Not studied. Based on the extent of 
inhibition by lopinavir/ritonavir, 
saquinavir/ritonavir or 
atazanavir/ritonavir in the absence of 
etravirine, an increased exposure is 
expected.  

ANTIBIOTICS 



 
 
 

12 
 

Sulphamethoxazole/ 
Trimethoprim 
800 mg/160 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↔ 1.11  
Maraviroc Cmax: ↔ 1.19  
Sulphamethoxazole/trimethoprim 
concentrations not measured, no 
effect expected. 

CELSENTRI 300 mg 
twice daily and 
sulphamethoxazole/ 
trimethoprim can be 
co-administered without 
dose adjustment. 

Rifampicin 600 mg QD 
(maraviroc 100 mg BID) 
 
 
 
 
 
 
 
 

Maraviroc AUC: ↓ 0.37  
Maraviroc Cmax: ↓ 0.34  
Rifampicin concentrations not 
measured, no effect expected. 

CELSENTRI dose should 
be increased to 600 mg 
twice daily when 
co-administered with 
rifampicin in the absence 
of a potent CYP3A4 
inhibitor. This dose 
adjustment has not been 
studied in HIV patients. 
See also section 4.4.  

Rifampicin + efavirenz Combination with two inducers has 
not been studied. There may be a risk 
of suboptimal levels with risk of loss 
of virologic response and resistance 
development. 

Concomitant use of 
CELSENTRI and 
rifampicin + efavirenz is 
not recommended. 

Rifabutin + PI 
 
 
 
 
 
 
 
 
 
 
 
 
 

Not studied. Rifabutin is considered 
to be a weaker inducer than 
rifampicin. When combining 
rifabutin with protease inhibitors that 
are potent inhibitors of CYP3A4 a 
net inhibitory effect on maraviroc is 
expected. 

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when 
co-administered with 
rifabutin and a PI (except 
tipranavir/ritonavir where 
the dose should be 300 mg 
twice daily). See also 
section 4.4. 
 
Concomitant use of 
CELSENTRI and 
fosamprenavir/ritonavir is 
not recommended. 

Clarithromycin, 
Telithromycin 

Not studied, but both are potent 
CYP3A4 inhibitors and would be 
expected to increase maraviroc 
concentrations. 

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when 
co-administered with 
clarithromycin and 
telithromycin. 

ANTICONVULSANTS 
Carbamezepine, 
Phenobarbital, 
Phenytoin 

Not studied, but these are potent 
CYP3A4 inducers and would be 
expected to decrease maraviroc 
concentrations. 

CELSENTRI dose should 
be increased to 600 mg 
twice daily when co-
administered with 
carbamazepine, 
phenobarbital or 
phenytoin in the absence 
of a potent CYP3A4 
inhibitor. 

ANTIFUNGALS 



 
 
 

13 
 

Ketoconazole 400 mg QD 
(maraviroc 100 mg BID) 

Maraviroc AUCtau: ↑ 5.00  
Maraviroc Cmax: ↑ 3.38  
Ketoconazole concentrations not 
measured, no effect is expected. 

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when 
co-administered with 
ketoconazole. 

Itraconazole  Not studied. Itraconazole, is a potent 
CYP3A4 inhibitor and would be 
expected to increase the exposure of 
maraviroc. 

CELSENTRI dose should 
be decreased to 150 mg 
twice daily when 
co-administered with 
itraconazole. 

Fluconazole Fluconazole is considered to be a 
moderate CYP3A4 inhibitor. 
Population PK studies suggest that a 
dose adjustment of maraviroc is not 
required. 

CELSENTRI 300 mg 
twice daily should be 
administered with caution 
when co-administered 
with fluconazole. 

ANTIVIRALS 
Anti-HBV 
Pegylated interferon Pegylated interferon has not been 

studied, no interaction is expected. 
CELSENTRI 300 mg 
twice daily and pegylated 
interferon can be 
co-administered without 
dose adjustment. 

Anti-HCV 
Ribavirin Ribavirin has not been studied, no 

interaction is expected. 
CELSENTRI 300 mg 
twice daily and ribavirin 
can be co-administered 
without dose adjustment. 

DRUG ABUSE 
Methadone Not studied, no interaction expected. CELSENTRI 300 mg 

twice daily and methadone 
can be co-administered 
without dose adjustment.  

Buprenorphine Not studied, no interaction expected. CELSENTRI 300 mg 
twice daily and 
buprenorphine can be 
co-administered without 
dose adjustment.  

LIPID LOWERING  
MEDICINAL PRODUCTS 
Statins Not studied, no interaction expected. CELSENTRI 300 mg 

twice daily and statins can 
be co-administered 
without dose adjustment.  

ANTIARRHYTHMICS 
Digoxin 0.25 mg 
Single Dose 
(maraviroc 300 mg BID) 

Digoxin. AUCt: ↔ 1.00 
Digoxin. Cmax: ↔ 1.04  
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg 
twice daily and digoxin 
can be co-administered 
without dose adjustment. 
 
The effect of maraviroc on 
digoxin at the dose of 600 
mg BID has not been 
studied. 

ORAL CONTRACEPTIVES 



 
 
 

14 
 

Ethinylestradiol 30 mcg QD 
(maraviroc 100 mg BID) 

Ethinylestradiol. AUCt: ↔ 1.00 
Ethinylestradiol. Cmax: ↔ 0.99  
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg 
twice daily. and 
ethinylestradiol can be 
co-administered without 
dose adjustment. 

Levonorgestrel 150 mcg 
QD 
(maraviroc 100 mg BID) 

Levonorgestrel. AUC12: ↔ 0.98 
Levonorgestrel. Cmax: ↔ 1.01  
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg 
twice daily and 
levonorgestrel can be 
co-administered without 
dose adjustment. 

SEDATIVES 
Benzodiazepines   
Midazolam 7.5 mg Single 
Dose 
(maraviroc 300 mg BID) 

Midazolam. AUC: ↔ 1.18  
Midazolam. Cmax: ↔ 1.21 
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg 
twice daily and 
midazolam can be 
co-administered without 
dose adjustment. 

HERBAL PRODUCTS 
St. John’s Wort 
(Hypericum Perforatum) 

Co-administration of maraviroc with 
St. John's Wort is expected to 
substantially decrease maraviroc 
concentrations and may result in 
suboptimal levels and lead to loss of 
virologic response and possible 
resistance to maraviroc. 

Concomitant use of 
maraviroc and St. John's 
Wort or products 
containing St. John's Wort 
is not recommended. 

a Refer to Table 1 for maraviroc paediatric dosing recommendations when co-administered with antiretroviral therapy and other 
medicinal products. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are limited data from the use of maraviroc in pregnant women. The effect of maraviroc on 
human pregnancy is unknown. Studies in animals showed reproductive toxicity at high exposures. 
Primary pharmacological activity (CCR5 receptor affinity) was limited in the species studied (see 
section 5.3). Maraviroc should be used during pregnancy only if the expected benefit justifies the 
potential risk to the foetus. 
 
Breast-feeding 
 
It is unknown whether maraviroc is excreted in human milk. Available toxicological data in 
animals has shown extensive excretion of maraviroc in milk. Primary pharmacological activity 
(CCR5 receptor affinity) was limited in the species studied (see section 5.3). A risk to the 
newborn/infants cannot be excluded. 
 
It is recommended that mothers infected by HIV do not breast-feed their infants under any 
circumstances in order to avoid transmission of HIV. 
 
Fertility 
 
There is no data on the effects of maraviroc on human fertility. In rats, there were no adverse 
effects on male or female fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 



 
 
 

15 
 

Maraviroc may have a minor influence on the ability to drive and use machines. Patients should be 
informed that dizziness has been reported during treatment with maraviroc. The clinical status of 
the patient and the adverse reaction profile of maraviroc should be borne in mind when considering 
the patient's ability to drive, cycle or operate machinery.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Adults 
Assessment of treatment related adverse reactions is based on pooled data from two Phase 2b/3 
studies in treatment-experienced adult patients (MOTIVATE 1 and MOTIVATE 2) and one study 
in treatment-naïve adult patients (MERIT) infected with CCR5-tropic HIV-1 (see sections 4.4 and 
5.1).  
 
The most frequently reported adverse reactions occurring in the Phase 2b/3 studies were nausea, 
diarrhoea, fatigue and headache. These adverse reactions were common (≥ 1/100 to < 1/10).  
 
Tabulated list of adverse reactions 
 
The adverse reactions are listed by system organ class (SOC) and frequency. Within each 
frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon 
(≥1/1000 to <1/100), rare (≥1/10,000 to <1/1,000) , not known (cannot be estimated from the 
available data).  The adverse reactions and laboratory abnormalities presented below are not 
exposure adjusted. 
 
 
 
 
Table 3: Adverse reactions observed in clinical trials or post-marketing 

System Organ Class Adverse reaction Frequency 
Infections and infestations Pneumonia, oesophageal candidiasis uncommon 
Neoplasm benign, malignant and 
unspecified (including cysts and 
polyps) 

Bile duct cancer, diffuse large B-cell 
lymphoma, Hodgkin’s disease, 
metastases to bone, metastases to 
liver, metastases to peritoneum, 
nasopharyngeal cancer, oesophageal 
carcinoma 

rare 

Blood and lymphatic system 
disorders 

Anaemia common 
Pancytopenia, granulocytopenia rare 

Metabolism and nutrition disorders Anorexia common 
Psychiatric disorders Depression, insomnia common 
Nervous system disorders Seizures and seizure disorders uncommon 
Cardiac disorders Angina pectoris rare 
Vascular disorders Postural hypotension (see section 4.4) uncommon 
Gastrointestinal disorders Abdominal pain, flatulence, nausea  common 
Hepatobiliary disorders Alanine aminotransferase increased, 

aspartate aminotransferase increased 
common 

Hyperbilirubinaemia, gamma-
glutamyltransferase increased 

uncommon 

Hepatitis toxic, hepatic failure, 
hepatic cirrhosis, blood alkaline 
phosphatase increased 

rare 



 
 
 

16 
 

 
General disorders and 
administration site conditions 

Asthenia common 

 
 
Description of selected adverse reactions 
 
Delayed type hypersensitivity reactions, typically occurring within 2-6 weeks after start of therapy 
and including rash, fever, eosinophilia and liver reactions have been reported (see also section 4.4). 
Skin and liver reactions can occur as single events, or in combination. 
 
In HIV infected patients with severe immune deficiency at the time of initiation of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
infections may arise.  Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) 
have also been reported; however, the reported time to onset is more variable and these events can 
occur many months after initiation of treatment (see section 4.4). 
 
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged 
risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy 
(CART). The frequency of this is unknown (see section 4.4). 
 
Cases of syncope caused by postural hypotension have been reported. 
 
Laboratory abnormalities 
 
Table 4 shows the incidence ≥1% of Grade 3-4 Abnormalities (ACTG Criteria) based on the 
maximum shift in laboratory test values without regard to baseline values. 
 
Table 4: Incidence ≥1% of grade 3-4 abnormalities (ACTG criteria) based on maximum shift 
in laboratory test values without regard to baseline studies MOTIVATE 1 and MOTIVATE 2 
(pooled analysis, up to 48 weeks) 
 

Hepatic failure with allergic features very rare 
Skin and subcutaneous tissue 
disorders 

Rash common 
Stevens-Johnson syndrome / Toxic 
epidermal necrolysis 

rare / not known 

Musculoskeletal and connective 
tissue disorders 
 

Myositis, blood creatine 
phosphokinase increased 

uncommon 

Muscle atrophy rare 
Renal and urinary disorders Renal failure, proteinuria uncommon 



 
 
 

17 
 

 
Laboratory parameter 

 
 

 
Limit 

Maraviroc 300 mg 
twice daily  

+ OBT 
N =421* 

(%) 

Placebo + OBT  
 

N =207* 
(%) 

Hepatobiliary disorders    
Aspartate aminotransferase >5.0x ULN 4.8 2.9 
Alanine aminotransferase >5.0x ULN 2.6 3.4 
Total bilirubin >5.0x ULN 5.5 5.3 
Gastrointestinal disorders    
Amylase >2.0x ULN 5.7 5.8 
Lipase >2.0x ULN 4.9 6.3 
Blood and lymphatic system disorders   
Absolute neutrophil count <750/mm3 4.3 1.9 

ULN: Upper Limit of Normal 
OBT: Optimised Background Therapy 
* Percentages based on total patients evaluated for each laboratory parameter 
 
The MOTIVATE studies were extended beyond 96 weeks, with an observational phase extended to 
5 years in order to assess the long term safety of maraviroc. The Long Term Safety/Selected 
Endpoints (LTS/SE) included death, AIDS-defining events, hepatic failure, Myocardial 
infarction/cardiac ischaemia, malignancies, rhabdomyolysis and other serious infectious events 
with maraviroc treatment.  The incidence of these selected endpoints for subjects on maraviroc in 
this observational phase was consistent with the incidence seen at earlier timepoints in the studies. 
 
In treatment-naïve patients, the incidence of grade 3 and 4 laboratory abnormalities using ACTG 
criteria was similar among the maraviroc and efavirenz treatment groups. 
 
Paediatric population 
 
The adverse reaction profile in paediatric patients is based on 48 Week safety data from study 
A4001031 in which 103 HIV-1 infected, treatment-experienced patients aged 2 to <18 years 
received maraviroc twice-daily with optimised background therapy (OBT). Overall, the safety 
profile in paediatric patients was similar to that observed in adult clinical studies. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms 
 
The highest dose administered in clinical studies was 1,200 mg. The dose limiting adverse reaction 
was postural hypotension.  
 
Prolongation of the QT interval was seen in dogs and monkeys at plasma concentrations 6 and 12 
times, respectively, those expected in humans at the maximum recommended dose of 300 mg twice 
daily. However, no clinically significant QT prolongation compared to placebo + OBT was seen in 
the Phase 3 clinical studies using the recommended dose of maraviroc or in a specific 
pharmacokinetic study to evaluate the potential of maraviroc to prolong the QT interval.  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 
 
 

18 
 

Management 
 
There is no specific antidote for overdose with maraviroc. Treatment of overdose should consist of 
general supportive measures including keeping the patient in a supine position, careful assessment 
of patient vital signs, blood pressure and ECG. 
 
If indicated, elimination of unabsorbed active maraviroc should be achieved by emesis or gastric 
lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed 
active substance. Since maraviroc is moderately protein bound, dialysis may be beneficial in 
removal of this medicine. Further management should be as recommended by the national poisons 
centre, where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, other antivirals, ATC code: J05AX09 
 
Mechanism of action 
 
Maraviroc is a member of a therapeutic class called CCR5 antagonists. Maraviroc selectively binds 
to the human chemokine receptor CCR5, preventing CCR5-tropic HIV-1 from entering cells. 
 
Antiviral activity in vitro 
 
Maraviroc has no antiviral activity in vitro against viruses which can use CXCR4 as their entry co-
receptor (dual-tropic or CXCR4-tropic viruses, collectively termed ‘CXCR4-using’ virus below). 
The serum adjusted EC90 value in 43 primary HIV-1 clinical isolates was 0.57 (0.06 – 10.7) ng/mL 
without significant changes between different subtypes tested. The antiviral activity of maraviroc 
against HIV-2 has not been evaluated. For details please refer to the pharmacology section of the 
CELSENTRI European Public Assessment Report (EPAR) on the European Medicines Agency 
(EMA) website.  
 
When used with other antiretroviral medicinal products in cell culture, the combination of 
maraviroc was not antagonistic with a range of NRTIs, NNRTIs, PIs or the HIV fusion inhibitor 
enfuvirtide.  
 
Virologic Escape 
 
Virologic escape from maraviroc can occur via 2 routes: the emergence of pre-existing virus which 
can use CXCR4 as its entry co-receptor (CXCR4-using virus) or the selection of virus that 
continues to use exclusively drug-bound CCR5 (CCR5-tropic virus).  
 
In vitro 
 
HIV-1 variants with reduced susceptibility to maraviroc have been selected in vitro, following 
serial passage of two CCR5-tropic viruses (0 laboratory strains, 2 clinical isolates). The maraviroc-
resistant viruses remained CCR5-tropic and there was no conversion from a CCR5-tropic virus to a 
CXCR4-using virus.  
 
Phenotypic resistance 
 
Concentration response curves for the maraviroc-resistant viruses were characterized 
phenotypically by curves that did not reach 100% inhibition in assays using serial dilutions of 
maraviroc (<100% maximal percentage inhibition (MPI)). Traditional IC50/IC90 fold-change was 



 
 
 

19 
 

not a useful parameter to measure phenotypic resistance, as those values were sometimes 
unchanged despite significantly reduced sensitivity. 
 
Genotypic resistance  
 
Mutations were found to accumulate in the gp120 envelope glycoprotein (the viral protein that 
binds to the CCR5 co-receptor). The position of these mutations was not consistent between 
different isolates. Hence, the relevance of these mutations to maraviroc susceptibility in other 
viruses is not known. 
 
Cross-resistance in vitro  
 
HIV-1 clinical isolates resistant to NRTIs, NNRTIs, PIs and enfuvirtide were all susceptible to 
maraviroc in cell culture. Maraviroc-resistant viruses that emerged in vitro remained sensitive to 
the fusion inhibitor enfuvirtide and the PI, saquinavir. 
 
In vivo 
Treatment-Experienced Adult Patients 
 
In the pivotal studies (MOTIVATE 1 and MOTIVATE 2), 7.6% of patients had a change in 
tropism result from CCR5-tropic to CXCR4-tropic or dual/mixed-tropic between screening and 
baseline (a period of 4-6 weeks).  
 
Failure with CXCR4-using virus 
 
CXCR4-using virus was detected at failure in approximately 60% of subjects who failed treatment 
on maraviroc, as compared to 6% of subjects who experienced treatment failure in the placebo + 
OBT arm. To investigate the likely origin of the on-treatment CXCR4-using virus, a detailed clonal 
analysis was conducted on virus from 20 representative subjects (16 subjects from the maraviroc 
arms and 4 subjects from the placebo + OBT arm) in whom CXCR4-using virus was detected at 
treatment failure. This analysis indicated that CXCR4-using virus emerged from a pre-existing 
CXCR4-using reservoir not detected at baseline, rather than from mutation of CCR5-tropic virus 
present at baseline. An analysis of tropism following failure of maraviroc therapy with CXCR4-
using virus in patients with CCR5 virus at baseline, demonstrated that the virus population reverted 
back to CCR5 tropism in 33 of 36 patients with more than 35 days of follow-up.  
 
At the time of failure with CXCR4-using virus, the resistance pattern to other antiretrovirals 
appears similar to that of the CCR5-tropic population at baseline, based on available data. Hence, 
in the selection of a treatment regimen, it should be assumed that viruses forming part of the 
previously undetected CXCR4 -using population (i.e. minor viral population) harbours the same 
resistance pattern as the CCR5-tropic population.  
 
Failure with CCR5-tropic virus 
 
Phenotypic resistance  
 
In patients with CCR5-tropic virus at time of treatment failure with maraviroc, 22 out of 58 
patients had virus with reduced sensitivity to maraviroc. In the remaining 36 patients, there was no 
evidence of virus with reduced sensitivity as identified by exploratory virology analyses on a 
representative group. The latter group had markers correlating to low compliance (low and variable 
drug levels and often a calculated high residual sensitivity score of the OBT). In patients failing 
therapy with CCR5-tropic virus only, maraviroc might be considered still active if the MPI value is 
≥95% (PhenoSense Entry assay). Residual activity in vivo for viruses with MPI-values <95% has 
not been determined. 
 
Genotypic resistance 



 
 
 

20 
 

A relatively small number of individuals receiving maraviroc-containing therapy have failed with 
phenotypic resistance (i.e. the ability to use drug-bound CCR5 with MPI <95%).   To date, no 
signature mutation(s) have been identified.  The gp120 amino acid substitutions identified so far 
are context dependent and inherently unpredictable with regards to maraviroc susceptibility.   
Treatment-Experienced Paediatric Patients  
 
In the Week 48 analysis (N=103), non-CCR5 tropic-virus was detected in 5/23 (22%) subjects at 
virologic failure. One additional subject had CCR5 tropic-virus with reduced susceptibility to 
maraviroc at virologic failure, although this was not retained at the end of treatment.  Subjects with 
virologic failure generally appeared to have low compliance to both maraviroc and the background 
antiretroviral elements of their regimens. Overall, the mechanisms of resistance to maraviroc 
observed in this treatment-experienced paediatric population were similar to those observed in 
adult populations. 
 
Clinical results 
 
Studies in Treatment-Experienced Adult Patients Infected with CCR5-tropic Virus 
 
The clinical efficacy of maraviroc (in combination with other antiretroviral medicinal products) on 
plasma HIV RNA levels and CD4+ cell counts have been investigated in two pivotal randomized, 
double blind, multicentre studies (MOTIVATE 1 and MOTIVATE 2, n=1076) in patients infected 
with CCR5 tropic HIV-1 as determined by the Monogram Trofile Assay. 
 
Patients who were eligible for these studies had prior exposure to at least 3 antiretroviral medicinal 
product classes [≥1 NRTIs, ≥1 NNRTIs, ≥2 PIs, and/or enfurvirtide] or documented resistance to at 
least one member of each class. Patients were randomised in a 2:2:1 ratio to maraviroc 300 mg 
(dose equivalence) once daily, twice daily or placebo in combination with an optimized 
background consisting of 3 to 6 antiretroviral medicinal products (excluding low-dose ritonavir). 
The OBT was selected on the basis of the subject’s prior treatment history and baseline genotypic 
and phenotypic viral resistance measurements.  
 
Table 5: Demographic and baseline characteristics of patients (pooled studies MOTIVATE 1 
and MOTIVATE 2) 
 

 
Demographic and Baseline Characteristics 

Maraviroc 300 mg 
twice daily 

+ OBT 
 

N = 426 

Placebo + OBT  
 
 

N = 209 

Age (years) 
(Range, years) 

46.3 
21-73 

45.7 
29-72 

Male Sex 89.7% 88.5% 
Race (White/Black/Other) 85.2% / 12% / 2.8% 85.2% / 12.4% / 2.4% 
Mean Baseline HIV-1 RNA (log10 copies/mL) 4.85 4.86 
Median Baseline CD4+ Cell Count (cells/mm3)  
(range, cells/mm3) 

166.8 
(2.0-820.0) 

171.3 
(1.0-675.0) 

Screening Viral Load >100,000 copies/mL 179 (42.0%) 84 (40.2%) 
Baseline CD4+ Cell Count ≤200 cells/mm3 250 (58.7%) 118 (56.5%) 
Number (Percentage) of patients with GSS score1: 
 0 
 1 
 2 
 ≥3 

 
102 (23.9%) 
138 (32.4%) 
80 (18.8%) 

104 (24.4%) 

 
51 (24.4%) 
53 (25.4%) 
41 (19.6%) 
59 (28.2%) 

1Based on GeneSeq resistance assay.  
 



 
 
 

21 
 

Limited numbers of patients from ethnicities other than Caucasian were included in the pivotal 
clinical studies, therefore very limited data are available in these patient populations. 
 
The mean increase in CD4+ cell count from baseline in patients who failed with a change in 
tropism result to dual/mixed tropic or CXCR4, in the maraviroc 300 mg twice daily + OBT 
(+56 cells/mm3) group was greater than that seen in patients failing placebo + OBT 
(+13.8 cells/mm3) regardless of tropism. 
 
Table 6: Efficacy Outcomes at week 48 (pooled studies MOTIVATE 1 and MOTIVATE 2) 
 

Outcomes Maraviroc 300 mg 
twice daily 

+ OBT 
   N=426 

Placebo + 
OBT  

 
N=209 

Difference1 
 (Confidence 

Interval2) 

HIV-1 RNA 
Mean change from baseline 
(log copies/mL) 

 
-1.837 

 

 
-0.785 

 
-1.055 

(-1.327, -0.783) 
Percentage of patients with 
HIV-1 RNA <400 copies/mL 

56.1% 
 

22.5% Odds ratio: 4.76 
(3.24, 7.00) 

Percentage of patients with 
HIV-1 RNA <50 copies/mL 

45.5% 
 

16.7% Odds ratio: 4.49 
(2.96, 6.83) 

CD4+ cell count 
Mean change from baseline 
(cells/µL) 

 
122.78 

 

 
59.17 

 

 
63.13 

(44.28, 81.99)2 
1 p-values < 0.0001 
2 For all efficacy endpoints the confidence intervals were 95%, except for HIV-1 RNA Change 
from baseline, which was 97.5% 
 
In a retrospective analysis of the MOTIVATE studies with a more sensitive assay for screening of 
tropism (Trofile ES), the response rates (<50 copies/mL at week 48) in patients with only CCR5-
tropic virus detected at baseline was 48.2% in those treated with maraviroc + OBT (n=328), and 
16.3% in those treated with placebo + OBT (n=178). 
 
Maraviroc 300 mg twice daily + OBT was superior to placebo + OBT across all subgroups of 
patients analysed (see Table 7). Patients with very low CD4+ count at baseline (i.e. <50 cells/µL) 
had a less favourable outcome. This subgroup had a high degree of bad prognostic markers, i.e. 
extensive resistance and high baseline viral loads. However, a significant treatment benefit for 
maraviroc compared to placebo + OBT was still demonstrated (see Table 7). 
 
Table 7: Proportion of patients achieving <50 copies/mL at Week 48 by subgroup (pooled 
Studies MOTIVATE 1 and MOTIVATE 2) 
 

 
 

Subgroups 

HIV-1 RNA <50 copies/mL 
Maraviroc 300 mg 
twice daily + OBT 

N=426 

Placebo + OBT 
 

N=209 
Screening HIV-1 RNA (copies /mL):  

<100,000 
≥100,000 

  
58.4% 
 34.7% 

 
 26.0% 
9.5% 

Baseline CD4+ (cells/µL):   
 <50 
50-100 
101-200 
201-350 
≥ 350 

 
16.5% 
36.4% 
56.7% 
57.8% 
72.9% 

 
2.6% 

12.0% 
21.8% 
21.0% 
38.5% 



 
 
 

22 
 

Number of active ARVs in OBT1: 
0  
1  
2  
≥3  

 
32.7% 
 44.5% 
 58.2% 
 62% 

 
2.0% 
7.4% 

31.7% 
38.6% 

1Based on GSS. 
 
Studies in Treatment-Experienced Adult Patients Infected with Non-CCR5-tropic Virus 
 
Study A4001029 was an exploratory study in patients infected with dual/mixed or CXCR4 tropic 
HIV-1 with a similar design as the studies MOTIVATE 1 and MOTIVATE 2. Use of maraviroc 
was not associated with a significant decrease in HIV 1 RNA compared with placebo in these 
subjects and no adverse effect on CD4+ cell count was noted.   
 
Studies in Treatment-Naïve Adult Patients Infected with CCR5-tropic Virus 
 
A randomised, double-blinded study (MERIT), explored maraviroc versus efavirenz, both in 
combination with zidovudine/lamivudine (n=721, 1:1). After 48 weeks of treatment, maraviroc did 
not reach non-inferiority to efavirenz for the endpoint of HIV-1 RNA < 50 copies/mL (65.3 vs. 
69.3 % respectively, lower confidence bound -11.9%). More patients treated with maraviroc 
discontinued due to lack of efficacy (43 vs.15) and among patients with lack of efficacy, the 
proportion acquiring NRTI resistance (mainly lamivudine) was higher in the maraviroc arm. Fewer 
patients discontinued maraviroc due to adverse events (15 vs. 49). 
 
Studies in Adult Patients Co-infected with Hepatitis B and/or Hepatitis C virus  
 
The hepatic safety of maraviroc in combination with other antiretroviral agents in CCR5-tropic 
HIV-1-infected subjects with HIV RNA <50 copies/mL, co-infected with Hepatitis C and/or 
Hepatitis B Virus was evaluated in a multicentre, randomized, double blinded, placebo-controlled 
study. 70 subjects (Child-Pugh Class A, n=64; Child-Pugh Class B, n=6) were randomized to the 
maraviroc group and 67 subjects (Child-Pugh Class A, n=59; Child-Pugh Class B, n=8) were 
randomized to the placebo group.  
 
The primary objective assessed the incidence of Grade 3 and 4 ALT abnormalities (>5x upper limit 
of normal (ULN) if baseline ALT ≤ ULN; or >3.5x baseline if baseline ALT > ULN) at Week 48. 
One subject in each treatment arm met the primary endpoint by Week 48 (at Week 8 for placebo 
and Week 36 for the maraviroc arm).   
 
Studies in Treatment-Experienced Paediatric Patients Infected with CCR5-tropic Virus 
 
Study A4001031 is an open-label, multicenter trial in paediatric patients (aged 2 years to less than 
18 years) infected with CCR5-tropic HIV-1, determined by the enhanced-sensitivity Trofile assay.  
Subjects were required to have HIV-1 RNA greater than 1,000 copies per mL at Screening.  
 
All subjects (n = 103) received maraviroc twice daily and OBT.  Maraviroc dosing was based on 
body surface area and doses were adjusted based on whether the subject was receiving potent 
CYP3A inhibitors and/or inducers.  
 
In paediatric patients with a successful tropism test, dual mixed/CXCR4-tropic virus was detected 
in around 40% of screening samples (8/27, 30% in 2-6 year-olds, 31/81, 38% in 6-12 year-olds and 
41/90, 46% in 12-18 year-olds), underscoring the importance of tropism testing also in the 
paediatric population. 
 

The population was 52% female and 69% black, with mean age of 10 years (range: 2 years to 
17 years). At baseline, mean plasma HIV-1 RNA was 4.3 log10 copies/mL (range 2.4 to 6.2 log10 



 
 
 

23 
 

copies per mL), mean CD4+ cell count was 551 cells/mm3 (range 1 to 1654 cells/mm3) and mean 
CD4+ % was 21% (range 0% to 42%).  
 
At 48 weeks, using a missing, switch or discontinuation equals failure analysis, 48% of subjects 
treated with maraviroc and OBT achieved plasma HIV-1 RNA less than 48 copies/mL and 65% of 
subjects achieved plasma HIV-1 RNA less than 400 copies per mL. The mean CD4+ cell count 
(percent) increase from baseline to Week 48 was 247 cells/mm3 (5%). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The absorption of maraviroc is variable with multiple peaks. Median peak maraviroc plasma 
concentrations are attained at 2 hours (range 0.5-4 hours) following single oral doses of 300 mg 
commercial tablet administered to healthy volunteers. The pharmacokinetics of oral maraviroc are 
not dose proportional over the dose range. The absolute bioavailability of a 100 mg dose is 23% 
and is predicted to be 33% at 300 mg. Maraviroc is a substrate for the efflux transporter P-
glycoprotein. 

 
Co-administration of a 300 mg tablet with a high fat breakfast reduced maraviroc Cmax and AUC by 
33% and co-administration of 75 mg of oral solution with a high fat breakfast reduced maraviroc 
AUC by 73% in adult healthy volunteers. Studies with the tablets demonstrated a reduced food-
effect at higher doses.  
 
There were no food restrictions in the adult studies (using tablet formulations) or in the paediatric 
study (using both tablet and oral solution formulations). The results did not indicate any relevant 
efficacy or safety concern related to either fed or fasted dosing conditions. Therefore, maraviroc 
tablets and oral solution can be taken with or without food at the recommended doses in adults, 
adolescents and children aged 2 years and older and weighing at least 10 kg (see section 4.2). 
 
Distribution  
 
Maraviroc is bound (approximately 76%) to human plasma proteins, and shows moderate affinity 
for albumin and alpha-1 acid glycoprotein. The volume of distribution of maraviroc is 
approximately 194 L.  
 
Biotransformation  
 
Studies in humans and in vitro studies using human liver microsomes and expressed enzymes have 
demonstrated that maraviroc is principally metabolized by the cytochrome P450 system to 
metabolites that are essentially inactive against HIV-1. In vitro studies indicate that CYP3A4 is the 
major enzyme responsible for maraviroc metabolism. In vitro studies also indicate that 
polymorphic enzymes CYP2C9, CYP2D6 and CYP2C19 do not contribute significantly to the 
metabolism of maraviroc.  
 
Maraviroc is the major circulating component (approximately 42% radioactivity) following a single 
oral dose of 300 mg. The most significant circulating metabolite in humans is a secondary amine 
(approximately 22% radioactivity) formed by N-dealkylation. This polar metabolite has no 
significant pharmacological activity. Other metabolites are products of mono-oxidation and are 
only minor components of plasma radioactivity. 
 
Elimination 
 
A mass balance/excretion study was conducted using a single 300 mg dose of 14C-labeled 
maraviroc. Approximately 20% of the radiolabel was recovered in the urine and 76% was 
recovered in the faeces over 168 hours. Maraviroc was the major component present in urine (mean 



 
 
 

24 
 

of 8% dose) and faeces (mean of 25% dose). The remainder was excreted as metabolites. After 
intravenous administration (30 mg), the half-life of maraviroc was 13.2 h, 22% of the dose was 
excreted unchanged in the urine and the values of total clearance and renal clearance were 44.0 L/h 
and 10.17 L/h respectively. 
 
Special patient populations: 
 
Paediatric population 
 
Intensive pharmacokinetics of maraviroc were evaluated in 50 treatment-experienced, CCR5-
tropic, HIV-1 infected paediatric patients aged 2 to 18 years (weight 10.0 to 57.6 kg) in the dose-
finding stage of clinical trial A4001031. Doses were given with food on intensive pharmacokinetic 
evaluation days and optimised to achieve an average concentration over the dosing interval (Cavg) 
of greater than 100 ng/mL; otherwise, maraviroc was given with or without food. The initial dose 
of maraviroc was scaled from adult doses using a body surface area (BSA) of 1.73 m2 to children 
and adolescent BSA (m2)-based bands. In addition, dosing was based on whether subjects were 
receiving potent CYP3A inhibitors (38/50), potent CYP3A inducers (2/50) or other concomitant 
medicinal products that are not potent CYP3A inhibitors or potent CYP3A inducers (10/50) as part 
of OBT. Sparse pharmacokinetics were evaluated in all subjects including the additional 47 
subjects receiving potent CYP3A inhibitors that did not take part in the dose-finding stage. The 
impact of potent CYP3A inhibitors and/or inducers on maraviroc pharmacokinetic parameters in 
paediatric patients was similar to that observed in adults. 
 
BSA (m2)-based bands have been modified to weight (kg)-based bands to simplify dosing and 
reduce dosing errors (see section 4.2). Use of weight (kg)-based doses in treatment-experienced 
HIV-1-infected children and adolescents results in maraviroc exposures similar to those observed 
in treatment-experienced adults receiving recommended doses with concomitant medications. The 
pharmacokinetics of maraviroc in paediatric patients below 2 years of age have not been 
established (see section 4.2). 
 
Elderly  
 
Population analysis of the Phase 1/2a and Phase 3 studies (16-65 years of age) has been conducted 
and no effect of age have been observed (see section 4.2). 
  
Renal impairment 
 
 A study compared the pharmacokinetics of a single 300 mg dose of maraviroc in subjects with 
severe renal impairment (CLcr < 30 mL/min, n=6) and end stage renal disease (ESRD) to healthy 
volunteers (n=6). The geometric mean AUCinf (CV%) for maraviroc was as follows: healthy 
volunteers (normal renal function) 1348.4 ng·h/mL (61%); severe renal impairment 4367.7 
ng·h/mL (52%); ESRD (dosing after dialysis) 2677.4 ng·h/mL (40%); and ESRD (dosing before 
dialysis) 2805.5 ng·h/mL (45%). The C max (CV%) was 335.6 ng/mL (87%) in healthy volunteers 
(normal renal function); 801.2 ng/mL (56%) in severe renal impairment; 576.7 ng/mL (51%) in 
ESRD (dosing after dialysis) and 478.5 ng/mL (38%) in ESRD (dosing before dialysis). Dialysis 
had a minimal effect on exposure in subjects with ESRD. Exposures observed in subjects with 
severe renal impairment and ESRD were within the range observed in single maraviroc 300 mg 
dose studies in healthy volunteers with normal renal function. Therefore, no dose adjustment is 
necessary in patients with renal impairment receiving maraviroc without a potent CYP3A4 
inhibitor (see sections 4.2, 4.4 and 4.5).  
 
In addition, the study compared the pharmacokinetics of multiple dose maraviroc in combination 
with saquinavir/ritonavir 1000/100 mg BID (a potent CYP3A4 inhibitor) for 7 days in subjects with 
mild renal impairment (CLcr >50 and ≤80 mL/min, n=6) and moderate renal impairment (CLcr 
≥30 and ≤50 mL/min, n=6) to healthy volunteers (n=6). Subjects received 150 mg of maraviroc at 



 
 
 

25 
 

different dose frequencies (healthy volunteers – every 12 hours; mild renal impairment – every 24 
hours; moderate renal impairment – every 48 hours). The average concentration (Cavg) of 
maraviroc over 24 hours was 445.1 ng/mL, 338.3 ng/mL, and 223.7 ng/mL for subjects with 
normal renal function, mild renal impairment, and moderate renal impairment, respectively. The 
Cavg of maraviroc from 24-48 hours for subjects with moderate renal impairment was low (Cavg: 
32.8 ng/mL). Therefore, dosing frequencies of longer than 24 hours in subjects with renal 
impairment may result in inadequate exposures between 24-48 hours.  
 
Dose adjustment is necessary in patients with renal impairment receiving maraviroc with potent 
CYP3A4 inhibitors (see sections 4.2 and 4.4 and 4.5). 
 
Hepatic impairment 
 
Maraviroc is primarily metabolized and eliminated by the liver. A study compared the 
pharmacokinetics of a single 300 mg dose of maraviroc in patients with mild (Child-Pugh Class A, 
n=8), and moderate (Child-Pugh Class B, n=8) hepatic impairment compared to healthy subjects 
(n=8). Geometric mean ratios for Cmax and AUClast were 11% and 25% higher respectively for 
subjects with mild hepatic impairment, and 32% and 46% higher respectively for subjects with 
moderate hepatic impairment compared to subjects with normal hepatic function. The effects of 
moderate hepatic impairment may be underestimated due to limited data in patients with decreased 
metabolic capacity and higher renal clearance in these subjects. The results should therefore be 
interpreted with caution. The pharmacokinetics of maraviroc has not been studied in subjects with 
severe hepatic impairment (see sections 4.2 and 4.4).  
  
Race  
 
No relevant difference between Caucasian, Asian and Black subjects has been observed. The 
pharmacokinetics in other races has not been evaluated. 
 
Gender  
 
No relevant differences in pharmacokinetics have been observed. 
 
 
Pharmacogenomics 
 
The pharmacokinetics of maraviroc is dependent on CYP3A5 activity and expression level, which 
can be modulated by genetic variation. Subjects with a functional CYP3A5 (CYP3A5*1 allele) 
have been shown to have a reduced exposure to maraviroc compared to subjects with defect 
CYP3A5 activity (e.g., CYP3A5*3, CYP3A5*6, and CYP3A5*7). The CYP3A5 allelic frequency 
depends on ethnicity: the majority of Caucasians (~90%) are poor metabolisers of CYP3A5 
substrates (i.e., subjects with no copy of functional CYP3A5 alleles) while approximately 40% of 
African-Americans and 70% of Sub-Saharan Africans are extensive metabolisers (i.e., subjects 
with two copies of functional CYP3A5 alleles). 
 
In a Phase 1 study conducted in healthy subjects, Blacks with a CYP3A5 genotype conferring 
extensive maraviroc metabolism (2 CYP3A5*1 alleles; n=12) had a 37% and 26% lower AUC 
when dosed with maraviroc 300 mg twice daily compared with Black (n=11) and Caucasian (n=12) 
subjects with CYP3A5 genotype conferring poor maraviroc metabolism (no CYP3A5*1 allele), 
respectively. The difference in maraviroc exposure between CYP3A5 extensive and poor 
metabolisers was reduced when maraviroc was administered together with a strong CYP3A 
inhibitor: extensive CYP3A5 metabolisers (n=12) had a 17% lower maraviroc AUC compared with 
poor CYP3A5 metabolisers (n=11) when dosed with maraviroc 150 mg once daily in the presence 
of darunavir/cobicistat (800/150 mg).  
 



 
 
 

26 
 

All subjects in the Phase 1 study achieved the Cavg concentrations that have been shown to be 
associated with near maximal virologic efficacy with maraviroc (75 ng/mL) in the Phase 3 study in 
treatment-naïve adult patients (MERIT).  Therefore, despite differences in CYP3A5 genotype 
prevalence by race, the effect of CYP3A5 genotype on maraviroc exposure is not considered 
clinically significant and no maraviroc dose adjustment according to CYP3A5 genotype, race or 
ethnicity is needed.  
 
5.3 Preclinical safety data 
 
Primary pharmacological activity (CCR5 receptor affinity) was present in the monkey (100% 
receptor occupancy) and limited in the mouse, rat, rabbit and dog. In mice and human beings that 
lack CCR5 receptors through genetic deletion, no significant adverse consequences have been 
reported. 
 
In vitro and in vivo studies showed that maraviroc has a potential to increase QTc interval at 
supratherapeutic doses with no evidence of arrhythmia.  
 
Repeated dose toxicity studies in rats identified the liver as the primary target organ for toxicity 
(increases in transaminases, bile duct hyperplasia, and necrosis). 
 
Maraviroc was evaluated for carcinogenic potential by a 6 month transgenic mouse study and a 24 
month study in rats. In mice, no statistically significant increase in the incidence of tumours was 
reported at systemic exposures from 7 to 39-times the human exposure (unbound AUC 0-24h 
measurement) at a dose of 300 mg twice daily. In rats, administration of maraviroc at a systemic 
exposure 21-times the expected human exposure produced thyroid adenomas associated with 
adaptive liver changes. These findings are considered of low human relevance. In addition, 
cholangiocarcinomas (2/60 males at 900 mg/kg) and cholangioma (1/60 females at 500 mg/kg) 
were reported in the rat study at a systemic exposure at least 15-times the expected free human 
exposure. 
 
Maraviroc was not mutagenic or genotoxic in a battery of in vitro and in vivo assays including 
bacterial reverse mutation, chromosome aberrations in human lymphocytes and mouse bone 
marrow micronucleus.  
 
Maraviroc did not impair mating or fertility of male or female rats, and did not affect sperm of 
treated male rats up to 1000 mg/kg. The exposure at this dose level corresponded to 39-fold the 
estimated free clinical AUC for a 300 mg twice daily dose.  
 
Embryofoetal development studies were conducted in rats and rabbits at doses up to 39- and 34-
fold the estimated free clinical AUC for a 300 mg twice daily dose. In rabbit, 7 foetuses had 
external anomalies at maternally toxic doses and 1 foetus at the mid dose of 75 mg/kg. 
 
Pre- and post-natal developmental studies were performed in rats at doses up to 27-fold the 
estimated free clinical AUC for a 300 mg twice daily dose. A slight increase in motor activity in 
high-dose male rats at both weaning and as adults was noted, while no effects were seen in females. 
Other developmental parameters of these offspring, including fertility and reproductive 
performance, were not affected by the maternal administration of maraviroc. 
 
6 PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
  
Cellulose, microcrystalline  
Calcium hydrogen phosphate, anhydrous  



 
 
 

27 
 

Sodium starch glycolate  
Magnesium stearate 
 
Film-coat  
 
Poly (vinyl alcohol) 
Titanium dioxide (E171) 
Macrogol 3350 
Talc 
Soya lecithin  
Indigo carmine aluminium lake (E132) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
5 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage condition. 
 
6.5 Nature and contents of container 
 
CELSENTRI 25 mg film-coated tablets 
 
High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an 
aluminium foil/polyethylene heat induction seal containing 120 film-coated tablets. 
  
CELSENTRI 75 mg film-coated tablets 
 
High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an 
aluminium foil/polyethylene heat induction seal containing 120 film-coated tablets. 
 
CELSENTRI 150 mg film-coated tablets 
 
High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an 
aluminium foil/polyethylene heat induction seal containing 180 film-coated tablets.  
 
Polyvinyl chloride (PVC) blisters with child-resistant (CR)  aluminium/polyethylene terephthalate 
(PET) lidding foil  in a carton containing 30, 60, 90 film-coated tablets and multipacks containing 
180 (2 packs of 90) film-coated tablets.  
 
CELSENTRI 300 mg film-coated tablets 
 
High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an 
aluminium foil/polyethylene heat induction seal containing 180 film-coated tablets. 
 
Polyvinyl chloride (PVC) blisters with child-resistant (CR)   aluminium/polyethylene terephthalate 
(PET) lidding foil in a carton containing 30, 60, 90 film-coated tablets and multipacks containing 
180 (2 packs of 90) film-coated tablets. 
 
Not all pack sizes may be marketed. 
 



 
 
 

28 
 

6.6 Special precautions for disposal  
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7 MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
CELSENTRI 25 mg film-coated tablets 
EU/1/07/418/011 
 
CELSENTRI 75 mg film-coated tablets 
EU/1/07/418/012 
 
CELSENTRI 150 mg film-coated tablets 
EU/1/07/418/001 (180 tablets) 
EU/1/07/418/002 (30 tablets) 
EU/1/07/418/003 (60 tablets) 
EU/1/07/418/004 (90 tablets)  
EU/1/07/418/005 (2 x 90 tablets - multipack) 
 
CELSENTRI 300 mg film-coated tablets 
EU/1/07/418/006 (180 tablets) 
EU/1/07/418/007 (30 tablets) 
EU/1/07/418/008 (60 tablets) 
EU/1/07/418/009 (90 tablets)  
EU/1/07/418/010 (2 x 90 tablets - multipack) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 18th September 2007 
Date of latest renewal: 20 July 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European 
Medicines Agency http://www.ema.europa.eu 



 
 
 

29 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 20 mg/ml oral solution 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of oral solution contains 20 mg maraviroc. 
  
For the full list of excipients, see section 6.1. 
 
3. PHARMACEUTICAL FORM 
 
Oral solution.  
 
Clear, colourless, oral solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
CELSENTRI, in combination with other antiretroviral medicinal products, is indicated for 
treatment-experienced adults, adolescents and children of 2 years of age, and older and weighing at 
least 10 kg infected with only CCR5-tropic HIV-1 detectable (see sections 4.2 and 5.1). 
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
Before taking CELSENTRI it has to be confirmed that only CCR5-tropic HIV-1 is detectable (i.e. 
CXCR4 or dual/mixed tropic virus not detected) using an adequately validated and sensitive 
detection method on a newly drawn blood sample. The Monogram Trofile assay was used in the 
clinical studies of CELSENTRI (see sections 4.4 and 5.1). The viral tropism cannot be safely 
predicted by treatment history and assessment of stored samples. 
 
There are currently no data regarding the reuse of CELSENTRI in patients that currently have only 
CCR5-tropic HIV-1 detectable, but have a history of failure on CELSENTRI (or other CCR5 
antagonists) with a CXCR4 or dual/mixed tropic virus. There are no data regarding the switch from 
a medicinal product of a different antiretroviral class to CELSENTRI in virologically suppressed 
patients. Alternative treatment options should be considered.  
 
Adults 
The recommended dose of CELSENTRI is 150 mg (with potent CYP3A inhibitor with or without a 
potent CYP3A inducer), 300 mg (without potent CYP3A inhibitors or inducers) or 600 mg twice 
daily (with potent CYP3A inducer without a potent CYP3A inhibitor) depending on interactions 
with concomitant antiretroviral therapy and other medicinal products (see section 4.5).  
 
Children from 2 years of age and weighing at least 10kg 
The recommended dose of CELSENTRI should be based on body weight (kg) and should not 
exceed the recommended adult dose. CELSENTRI oral solution (20 mg per mL) formulation 
should be prescribed if a child is unable to reliably swallow CELSENTRI tablets. 
 



 
 
 

30 
 

The recommended dose of CELSENTRI differs depending on interactions with concomitant 
antiretroviral therapy and other medicinal products. Refer to section 4.5 for corresponding adult 
dosage. 
 
Many medicines have profound effects on maraviroc exposure due to drug-drug interactions. Prior 
to deciding the dose of CELSENTRI by weight, please refer to Table 2 in section 4.5 to carefully 
determine the corresponding adult dose.  The corresponding paediatric dose can then be obtained 
from Table 1 below. If uncertainty still exists, contact a pharmacist for advice. 
 
Table 1. Recommended dosing regimen in children aged 2 years and above and weighing at 
least 10 kg 
 

Adult 
dosage* 

Concomitant 
Medications 

Dose of CELSENTRI in children based on weight 

10 to 
less than 20 kg 

20 to 
less than 

30 kg 

30 to 
less than  

40 kg 

at least 
40 kg 

150 mg twice 
daily 

CELSENTRI 
with products 
that are potent 
CYP3A 
inhibitors (with 
or without a 
CYP3A inducer) 

50 mg 
twice daily 

75 mg 
twice daily 

100 mg 
twice daily 

150 mg 
twice daily 

300 mg twice 
daily 

CELSENTRI 
with products 
that are not 
potent CYP3A 
inhibitors or 
potent CYP3A 
inducers 

  Data to support these doses are 
lacking. 

300 mg 
twice daily 

300 mg 
twice daily 

600 mg twice 
daily 

CELSENTRI 
with products 
that are CYP3A 
inducers (without 
a potent CYP3A 
inhibitor) 

Data to support these doses are lacking and CELSENTRI is not 
recommended in children taking concomitant interacting 
medicinal products that in adults would require a 600 mg twice 
daily dose. 

 

* Based on drug-drug interactions (refer to section 4.5) 
 
Special populations 
 
Elderly 
There is limited experience in patients >65 years of age (see section 5.2), therefore CELSENTRI 
should be used with caution in this population. 
 
Renal impairment  
In adult patients with a creatinine clearance of <80 mL/min, who are also receiving potent CYP3A4 
inhibitors, the dose interval of maraviroc should be adjusted to 150 mg once daily (see sections 4.4 
and 4.5).   
 
Examples of agents/regimens with such potent CYP3A4-inhibiting activity are: 
 

• ritonavir-boosted protease inhibitors (with the exception of tipranavir/ritonavir),  
• cobicistat,  
• itraconazole, voriconazole, clarithromycin and telithromycin, 



 
 
 

31 
 

• telaprevir and boceprevir. 
 
CELSENTRI should be used with caution in adult patients with severe renal impairment  
(CLcr <30 mL/min) who are receiving potent CYP3A4 inhibitors (see sections 4.4 and 5.2). 
 
There are no data available to recommend a specific dose in paediatric patients with renal 
impairment.  Therefore, CELSENTRI should be used with caution in this population. 
 
Hepatic impairment  
Limited data are available in adult patients with hepatic impairment and no data are available to 
recommend a specific dose for paediatric patients.  Therefore, CELSENTRI should be used with 
caution in patients with hepatic impairment (see sections 4.4 and 5.2).  
 
Paediatric patients (children younger than 2 years of age or weighing less than 10 kg) 
The safety and efficacy of CELSENTRI in children younger than 2 years of age or weighing less 
than 10 kg has not been established (see section 5.2). No data are available.  
 
Method of administration 
 
Oral use. 
CELSENTRI can be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
General 
 
While effective viral suppression with antiretroviral therapy has been proven to substantially 
reduce the risk of sexual transmission, a residual risk cannot be excluded.  Precautions to prevent 
transmission should be taken in accordance with national guidelines. 
 
Hepatic disease 
 
The safety and efficacy of maraviroc have not been specifically studied in patients with significant 
underlying liver disorders. 
 
Cases of hepatotoxicity and hepatic failure with allergic features have been reported in association 
with maraviroc. In addition, an increase in hepatic adverse reactions with maraviroc was observed 
during studies of treatment-experienced subjects with HIV infection, although there was no overall 
increase in ACTG Grade 3/4 liver function test abnormalities (see section 4.8). Hepatobiliary 
disorders reported in treatment-naïve patients were uncommon and balanced between treatment 
groups (see section 4.8). Patients with pre-existing liver dysfunction, including chronic active 
hepatitis, can have an increased frequency of liver function abnormalities during combination 
antiretroviral therapy and should be monitored according to standard practice. 
 
Discontinuation of maraviroc should be strongly considered in any patient with signs or symptoms 
of acute hepatitis, in particular if drug-related hypersensitivity is suspected or with increased liver 
transaminases combined with rash or other systemic symptoms of potential hypersensitivity (e.g. 
pruritic rash, eosinophilia or elevated IgE). 
 
There are limited data in patients with hepatitis B and/or C virus co-infection (see section 5.1). 
Caution should be exercised when treating these patients. In case of concomitant antiviral therapy 



 
 
 

32 
 

for hepatitis B and/or C, please refer to the relevant product information for these medicinal 
products. 
 
There is limited experience in patients with reduced hepatic function, therefore maraviroc should 
be used with caution in this population (see sections 4.2 and 5.2). 
 
Severe skin and hypersensitivity reactions 
 
Hypersensitivity reactions including severe and potentially life threatening events have been 
reported in patients taking maraviroc, in most cases concomitantly with other medicinal products 
associated with these reactions. These reactions included rash, fever, and sometimes organ 
dysfunction and hepatic failure. Discontinue maraviroc and other suspect agents immediately if 
signs or symptoms of severe skin or hypersensitivity reactions develop. Clinical status and relevant 
blood chemistry should be monitored and appropriate symptomatic therapy initiated. 
 
Cardiovascular safety 
 
Limited data exist with the use of maraviroc in patients with severe cardiovascular disease, 
therefore special caution should be exercised when treating these patients with maraviroc. In the 
pivotal studies of treatment-experienced patients coronary heart disease events were more common 
in patients treated with maraviroc than with placebo (11 during 609 PY vs 0 during 111 PY of 
follow-up). In treatment-naïve patients such events occurred at a similarly low rate with maraviroc 
and control (efavirenz). 
 
Postural hypotension 
 
When maraviroc was administered in studies with healthy volunteers at doses higher than the 
recommended dose, cases of symptomatic postural hypotension were seen at a greater frequency 
than with placebo. Caution should be used when administering maraviroc in patients on 
concomitant medicinal products known to lower blood pressure.  Maraviroc should also be used 
with caution in patients with severe renal insufficiency and in patients who have risk factors for, or 
have a history of postural hypotension.  Patients with cardiovascular co-morbidities could be at 
increased risk of cardiovascular adverse reactions triggered by postural hypotension. 
 
Renal impairment 
 
An increased risk of postural hypotension may occur in patients with severe renal insufficiency 
who are treated with potent CYP3A inhibitors or boosted protease inhibitors (PIs) and maraviroc. 
This risk is due to potential increases in maraviroc maximum concentrations when maraviroc is 
co-administered with potent CYP3A inhibitors or boosted PIs in these patients.  
 
Immune reconstitution syndrome 
 
In HIV infected patients with severe immune deficiency at the time of institution of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of CART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, 
and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii). Any 
inflammatory symptoms should be evaluated and treatment initiated when necessary. Autoimmune 
disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in 
the setting of immune reactivation; however, the reported time to onset is more variable and these 
events can occur many months after initiation of treatment. 
 



 
 
 

33 
 

Tropism 
 
Maraviroc should only be used when only CCR5-tropic HIV-1 is detectable (i.e. CXCR4 or 
dual/mixed tropic virus not detected) as determined by an adequately validated and sensitive 
detection method (see sections 4.1, 4.2 and 5.1). The Monogram Trofile assay was used in the 
clinical studies of maraviroc. The viral tropism cannot be predicted by treatment history or 
assessment of stored samples.  
 
Changes in viral tropism occur over time in HIV-1 infected patients. Therefore there is a need to 
start therapy shortly after a tropism test. 
 
Background resistance to other classes of antiretrovirals have been shown to be similar in previously 
undetected CXCR4-tropic virus of the minor viral population, as that found in CCR5-tropic virus. 
 
Maraviroc is not recommended to be used in treatment-naïve patients based on the results of a 
clinical study in this population (see section 5.1). 
 
Dose adjustment 
 
Physicians should ensure that appropriate dose adjustment of maraviroc is made when maraviroc is 
co-administered with potent CYP3A4 inhibitors and/or inducers since maraviroc concentrations 
and its therapeutic effects may be affected (see sections 4.2 and 4.5). Please also refer to the 
respective Summary of Product Characteristics of the other antiretroviral medicinal products used 
in the combination.  
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have 
been reported particularly in patients with advanced HIV-disease and/or long-term exposure to 
combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if 
they experience joint aches and pain, joint stiffness or difficulty in movement. 
 
Potential effect on immunity  
 
CCR5 antagonists could potentially impair the immune response to certain infections. This should 
be taken into consideration when treating infections such as active tuberculosis and invasive fungal 
infections. The incidence of AIDS-defining infections was similar between maraviroc and placebo 
arms in the pivotal studies.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Maraviroc is a metabolised by cytochrome P450 CYP3A4 and CYP3A5. Co-administration of 
maraviroc with medicinal products that induce CYP3A4 may decrease maraviroc concentrations 
and reduce its therapeutic effects. Co-administration of maraviroc with medicinal products that 
inhibit CYP3A4 may increase maraviroc plasma concentrations. Dose adjustment of maraviroc is 
recommended when maraviroc is co-administered with potent CYP3A4 inhibitors and/or inducers. 
Further details for concomitantly administered medicinal products are provided below (see Table 
2).  
 
Maraviroc is a substrate for the transporters P-glycoprotein and OATP1B1, but the effect of these 
transporters on the exposure to maraviroc is not known. 
   
Based on the in vitro and clinical data, the potential for maraviroc to affect the pharmacokinetics of 
co-administered medicinal products is low.  In vitro studies have shown that maraviroc does not 
inhibit OATP1B1, MRP2 or any of the major P450 enzymes at clinically relevant concentrations 



 
 
 

34 
 

(CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4). Maraviroc had no 
clinically relevant effect on the pharmacokinetics of midazolam, the oral contraceptives 
ethinylestradiol and levonorgestrel, or urinary 6β-hydroxycortisol/cortisol ratio, suggesting no 
inhibition or induction of CYP3A4 in vivo. At higher exposure of maraviroc a potential inhibition 
of CYP2D6 cannot be excluded.  
 
Renal clearance accounts for approximately 23% of total clearance of maraviroc when maraviroc is 
administered without CYP3A4 inhibitors. In vitro studies have shown that maraviroc does not 
inhibit any of the major renal uptake transporters at clinically relevant concentrations (OAT1, 
OAT3, OCT2, OCTN1, and OCTN2). Additionally, co-administration of maraviroc with tenofovir 
(substrate for renal elimination) and cotrimoxazole (contains trimethoprim, a renal cation transport 
inhibitor), showed no effect on the pharmacokinetics of maraviroc. In addition, co-administration 
of maraviroc with lamivudine/zidovudine showed no effect of maraviroc on lamivudine (primarily 
renally cleared) or zidovudine (non-P450 metabolism and renal clearance) pharmacokinetics.  
Maraviroc inhibits P-glycoprotein in vitro (IC50 is 183 μM). However, maraviroc does not 
significantly affect the pharmacokinetics of digoxin in vivo.  It may not be excluded that maraviroc 
can increase the exposure to the P-glycoprotein substrate dabigatran etexilate. 
 
Table 2: Interactions and adulta dose recommendations with other medicinal products 
 

Medicinal product by 
therapeutic areas 
(dose of CELSENTRI 
used in study) 

Effects on active substance levels 
Geometric mean change if not 
stated otherwise 

Recommendations 
concerning co-
administration in adults 

ANTI-INFECTIVES   
Antiretrovirals   
Pharmacokinetic Enhancers 
Cobicistat Interaction not studied. 

 
Cobicistat is a potent CYP3A 
inhibitor. 

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with cobicistat containing 
regimen. 

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) 
Lamivudine 150 mg BID 
(maraviroc 300 mg BID) 

Lamivudine AUC12: ↔ 1.13  
Lamivudine Cmax: ↔ 1.16  
Maraviroc concentrations not 
measured, no effect is expected. 

No significant interaction 
seen/expected. CELSENTRI 
300 mg twice daily and 
NRTIs can be 
co-administered without dose 
adjustment. 

Tenofovir 300 mg QD 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↔ 1.03 
Maraviroc Cmax: ↔ 1.03 
Tenofovir concentrations not 
measured, no effect is expected. 

Zidovudine 300 mg BID 
(maraviroc 300 mg BID) 

Zidovudine AUC12: ↔ 0.98  
Zidovudine Cmax: ↔ 0.92  
Maraviroc concentrations not 
measured, no effect is expected. 

Integrase Inhibitors   



 
 
 

35 
 

Elvitegravir/ritonavir 
150/100mg QD 
(maraviroc 150 mg BID) 

Maraviroc AUC12: ↑ 2.86 (2.33-3.51) 
Maraviroc Cmax: ↑ 2.15 (1.71-2.69) 
Maraviroc C12: ↑ 4.23 (3.47-5.16) 
 
Elvitegravir AUC24: ↔ 1.07 
(0.96-1.18) 
Elvitegravir Cmax: ↔ 1.01 (0.89-1.15) 
Elvitegravir C24: ↔ 1.09 (0.95-1.26) 
 

Elvitegravir as a single agent 
is indicated only in 
combination with certain 
ritonavir boosted PIs.  
 
Elvitegravir per se is not 
expected to affect maraviroc 
exposure to a clinically 
relevant degree and the 
observed effect is attributed to 
ritonavir.  
 
Thus, CELSENTRI dose 
should be modified in line 
with the recommendation for 
co-administration with 
respective PI/ritonavir 
combination (see ‘Protease 
Inhibitors’). 

Raltegravir 400 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↓ 0.86 
Maraviroc Cmax: ↓ 0.79  
 
Raltegravir AUC12: ↓ 0.63  
Raltegravir Cmax: ↓ 0.67  
Raltegravir C12: ↓ 0.72  
 

No clinically significant 
interaction seen. 
CELSENTRI 300 mg twice 
daily and raltegravir can be 
co-administered without dose 
adjustment. 

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 
Efavirenz 600 mg QD 
(maraviroc 100 mg BID) 

Maraviroc AUC12: ↓ 0.55  
Maraviroc Cmax: ↓ 0.49 
Efavirenz concentrations not 
measured, no effect is expected. 

CELSENTRI dose should be 
increased to 600 mg twice 
daily when co-administered 
with efavirenz in the absence 
of a potent CYP3A4 inhibitor. 
For combination with 
efavirenz + PI, see separate 
recommendations below. 

Etravirine 200 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↓ 0.47  
Maraviroc Cmax: ↓ 0.40  
 
Etravirine AUC12: ↔ 1.06  
Etravirine Cmax: ↔ 1.05 
Etravirine C12: ↔ 1.08 

Etravirine is only approved 
for use with boosted protease 
inhibitors. For combination 
with etravirine + PI, see 
below. 

Nevirapine 200 mg BID 
(maraviroc 300 mg Single 
Dose) 

Maraviroc AUC12: ↔ compared to 
historical controls 
Maraviroc Cmax: ↑ compared to 
historical controls 
Nevirapine concentrations not 
measured, no effect is expected. 

Comparison to exposure in 
historical controls suggests 
that CELSENTRI 300 mg 
twice daily and nevirapine 
can be co-administered 
without dose adjustment.  

Protease Inhibitors (PIs) 
Atazanavir 400 mg QD 
(maraviroc 300 mg BID) 

Maraviroc AUC12 ↑ 3.57  
Maraviroc Cmax: ↑ 2.09  
Atazanavir concentrations not 
measured, no effect is expected. 

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with a PI; except in 



 
 
 

36 
 

Atazanavir/ritonavir 
300 mg/100 mg QD 
(maraviroc 300 mg BID) 

Maraviroc AUC12 ↑ 4.88  
Maraviroc Cmax: ↑ 2.67  
Atazanavir/ritonavir concentrations 
not measured, no effect is expected. 

combination with 
tipranavir/ritonavir where the 
CELSENTRI dose should be 
300 mg BID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Lopinavir/ritonavir 
400 mg/100 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12 ↑ 3.95 
Maraviroc Cmax: ↑ 1.97 
Lopinavir/ritonavir concentrations not 
measured, no effect is expected. 

Saquinavir/ritonavir 
1000 mg/100 mg BID 
(maraviroc 100 mg BID) 

Maraviroc AUC12 ↑ 9.77  
Maraviroc Cmax: ↑ 4.78 
Saquinavir/ritonavir concentrations 
not measured, no effect is expected. 

Darunavir/ritonavir 
600 mg/100 mg BID 
(maraviroc 150 mg BID) 

Maraviroc AUC12 ↑ 4.05  
Maraviroc Cmax: ↑ 2.29  
Darunavir/ritonavir concentrations 
were consistent with historical data. 

Nelfinavir 
 

Limited data are available for co-
administration with nelfinavir. 
Nelfinavir is a potent CYP3A4 
inhibitor and would be expected to 
increase maraviroc concentrations. 

Indinavir 
 

Limited data are available for co-
administration with indinavir. 
Indinavir is a potent CYP3A4 
inhibitor. Population PK analysis in 
phase 3 studies suggests dose 
reduction of maraviroc when 
co-administered with indinavir gives 
appropriate maraviroc exposure. 

Tipranavir/ritonavir 
500 mg/200 mg BID 
(maraviroc 150 mg BID) 

Maraviroc AUC12 ↔ 1.02  
Maraviroc Cmax: ↔ 0.86  
Tipranavir/ritonavir concentrations 
were consistent with historical data. 

Fosamprenavir/ritonavir 
700 mg/100 mg BID 
(maraviroc 300 mg BID) 
 
 
 
 
 
 
 
 
 
 

Maraviroc AUC12: ↑ 2.49  
Maraviroc Cmax: ↑ 1.52  
Maraviroc C12: ↑ 4.74  
 
Amprenavir AUC12: ↓ 0.65  
Amprenavir Cmax: ↓ 0.66  
Amprenavir C12: ↓ 0.64  
 
Ritonavir AUC12: ↓ 0.66  
Ritonavir Cmax: ↓ 0.61  
Ritonavir C12: ↔ 0.86  
 
 
 

Concomitant use is not 
recommended. Significant 
reductions in amprenavir Cmin 
observed may result in 
virological failure in patients 
 

NNRTI + PI   
Efavirenz 600 mg QD + 
lopinavir/ritonavir 
400mg/100 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↑ 2.53 
Maraviroc Cmax: ↑ 1.25  
Efavirenz, lopinavir/ritonavir 
concentrations not measured, no 
effect expected. 

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with efavirenz and a PI 
(except tipranavir/ritonavir 



 
 
 

37 
 

Efavirenz 600 mg QD + 
saquinavir/ritonavir 
1000 mg/100 mg BID 
(maraviroc 100 mg BID) 

Maraviroc AUC12: ↑ 5.00  
Maraviroc Cmax: ↑ 2.26  
Efavirenz, saquinavir/ritonavir 
concentrations not measured, no 
effect expected. 

where the dose should be 600 
mg twice daily). 
Concomitant use of 
CELSENTRI and 
fosamprenavir/ritonavir is not 
recommended. Efavirenz and 

atazanavir/ritonavir or 
darunavir/ritonavir 

Not studied. Based on the extent of 
inhibition by atazanavir/ritonavir or 
darunavir/ritonavir in the absence of 
efavirenz, an increased exposure is 
expected.  

Etravirine and 
darunavir/ritonavir 
(maraviroc 150 mg BID) 

Maraviroc AUC12: ↑ 3.10  
Maraviroc Cmax: ↑ 1.77  
 
Etravirine AUC12: ↔ 1.00 
Etravirine Cmax: ↔ 1.08 
Etravirine C12: ↓ 0.81  
 
Darunavir AUC12: ↓ 0.86 
Darunavir Cmax: ↔ 0.96  
Darunavir C12: ↓ 0.77  
 
Ritonavir AUC12: ↔ 0.93  
Ritonavir Cmax: ↔ 1.02  
Ritonavir C12: ↓ 0.74  

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with etravirine and a PI. 
Concomitant use of 
CELSENTRI and 
fosamprenavir/ritonavir is not 
recommended. 

Etravirine and 
lopinavir/ritonavir, 
saquinavir/ritonavir or 
atazanavir/ritonavir 

Not studied. Based on the extent of 
inhibition by lopinavir/ritonavir, 
saquinavir/ritonavir or 
atazanavir/ritonavir in the absence of 
etravirine, an increased exposure is 
expected.  

ANTIBIOTICS 
Sulphamethoxazole/ 
Trimethoprim 
800 mg/160 mg BID 
(maraviroc 300 mg BID) 

Maraviroc AUC12: ↔ 1.11  
Maraviroc Cmax: ↔ 1.19  
Sulphamethoxazole/trimethoprim 
concentrations not measured, no 
effect expected. 

CELSENTRI 300 mg twice 
daily and sulphamethoxazole/ 
trimethoprim can be 
co-administered without dose 
adjustment. 

Rifampicin 600 mg QD 
(maraviroc 100 mg BID) 

Maraviroc AUC: ↓ 0.37  
Maraviroc Cmax: ↓ 0.34  
Rifampicin concentrations not 
measured, no effect expected. 

CELSENTRI dose should be 
increased to 600 mg twice 
daily when co-administered 
with rifampicin in the absence 
of a potent CYP3A4 inhibitor. 
This dose adjustment has not 
been studied in HIV patients. 
See also section 4.4.  

Rifampicin + efavirenz Combination with two inducers has 
not been studied. There may be a risk 
of suboptimal levels with risk of loss 
of virologic response and resistance 
development. 

Concomitant use of 
CELSENTRI and rifampicin 
+ efavirenz is not 
recommended. 



 
 
 

38 
 

Rifabutin + PI Not studied. Rifabutin is considered 
to be a weaker inducer than 
rifampicin. When combining rifabutin 
with protease inhibitors that are 
potent inhibitors of CYP3A4 a net 
inhibitory effect on maraviroc is 
expected. 

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with rifabutin and a PI 
(except tipranavir/ritonavir 
where the dose should be 300 
mg twice daily). See also 
section 4.4. 
Concomitant use of 
CELSENTRI and 
fosamprenavir/ritonavir is not 
recommended. 

Clarithromycin, 
Telithromycin 

Not studied, but both are potent 
CYP3A4 inhibitors and would be 
expected to increase maraviroc 
concentrations. 

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with clarithromycin and 
telithromycin. 

ANTICONVULSANTS 
Carbamezepine, 
Phenobarbital, 
Phenytoin 

Not studied, but these are potent 
CYP3A4 inducers and would be 
expected to decrease maraviroc 
concentrations. 

CELSENTRI dose should be 
increased to 600 mg twice 
daily when co-administered 
with carbamazepine, 
phenobarbital or phenytoin in 
the absence of a potent 
CYP3A4 inhibitor. 

ANTIFUNGALS 
Ketoconazole 400 mg QD 
(maraviroc 100 mg BID) 

Maraviroc AUCtau: ↑ 5.00 
Maraviroc Cmax: ↑ 3.38  
Ketoconazole concentrations not 
measured, no effect is expected. 

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with ketoconazole. 

Itraconazole  Not studied. Itraconazole, is a potent 
CYP3A4 inhibitor and would be 
expected to increase the exposure of 
maraviroc. 

CELSENTRI dose should be 
decreased to 150 mg twice 
daily when co-administered 
with itraconazole. 

Fluconazole Fluconazole is considered to be a 
moderate CYP3A4 inhibitor. 
Population PK studies suggest that a 
dose adjustment of maraviroc is not 
required. 

CELSENTRI 300 mg twice 
daily should be administered 
with caution when 
co-administered with 
fluconazole. 

ANTIVIRALS 
Anti-HBV 
Pegylated interferon Pegylated interferon has not been 

studied, no interaction is expected. 
CELSENTRI 300 mg twice 
daily and pegylated interferon 
can be co-administered 
without dose adjustment. 

Anti-HCV 
Ribavirin Ribavirin has not been studied, no 

interaction is expected. 
CELSENTRI 300 mg twice 
daily and ribavirin can be 
co-administered without dose 
adjustment. 

DRUG ABUSE 
Methadone Not studied, no interaction expected. CELSENTRI 300 mg twice 

daily and methadone can be 
co-administered without dose 
adjustment.  



 
 
 

39 
 

Buprenorphine Not studied, no interaction expected. CELSENTRI 300 mg twice 
daily and buprenorphine can 
be co-administered without 
dose adjustment.  

LIPID LOWERING  
MEDICINAL PRODUCTS 
Statins Not studied, no interaction expected. CELSENTRI 300 mg twice 

daily and statins can be 
co-administered without dose 
adjustment.  

ANTIARRHYTHMICS 
Digoxin 0.25 mg 
Single Dose 
(maraviroc 300 mg BID) 

Digoxin. AUCt: ↔ 1.00 
Digoxin. Cmax: ↔ 1.04  
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg twice 
daily and digoxin can be 
co-administered without dose 
adjustment. 
 
The effect of maraviroc on 
digoxin at the dose of 600 mg 
BID has not been studied. 

ORAL CONTRACEPTIVES 
Ethinylestradiol 30 mcg QD 
(maraviroc 100 mg BID) 

Ethinylestradiol. AUCt: ↔ 1.00  
Ethinylestradiol. Cmax: ↔ 0.99 
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg twice 
daily. and ethinylestradiol can 
be co-administered without 
dose adjustment. 

Levonorgestrel 150 mcg 
QD 
(maraviroc 100 mg BID) 

Levonorgestrel. AUC12: ↔ 0.98  
Levonorgestrel. Cmax: ↔ 1.01  
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg twice 
daily and levonorgestrel can 
be co-administered without 
dose adjustment. 

SEDATIVES 
Benzodiazepines   
Midazolam 7.5 mg Single 
Dose 
(maraviroc 300 mg BID) 

Midazolam. AUC: ↔ 1.18  
Midazolam. Cmax: ↔ 1.21  
Maraviroc concentrations not 
measured, no interaction expected. 

CELSENTRI 300 mg twice 
daily and midazolam can be 
co-administered without dose 
adjustment. 

HERBAL PRODUCTS 
St. John’s Wort 
(Hypericum Perforatum) 

Co-administration of maraviroc with 
St. John's Wort is expected to 
substantially decrease maraviroc 
concentrations and may result in 
suboptimal levels and lead to loss of 
virologic response and possible 
resistance to maraviroc. 

Concomitant use of maraviroc 
and St. John's Wort or 
products containing St. John's 
Wort is not recommended. 

a Refer to Table 1 for maraviroc paediatric dosing recommendations when co-administered with antiretroviral therapy and other 
medicinal products. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are limited data from the use of maraviroc in pregnant women. The effect of maraviroc on 
human pregnancy is unknown. Studies in animals showed reproductive toxicity at high exposures. 
Primary pharmacological activity (CCR5 receptor affinity) was limited in the species studied (see 
section 5.3). Maraviroc should be used during pregnancy only if the expected benefit justifies the 
potential risk to the foetus. 
 
Breast-feeding 



 
 
 

40 
 

 
It is unknown whether maraviroc is excreted in human milk. Available toxicological data in 
animals has shown extensive excretion of maraviroc in milk. Primary pharmacological activity 
(CCR5 receptor affinity) was limited in the species studied (see section 5.3). A risk to the 
newborn/infants cannot be excluded.  
 
It is recommended that mothers infected by HIV do not breast-feed their infants under any 
circumstances in order to avoid transmission of HIV. 
 
Fertility 
 
There is no data on the effects of maraviroc on human fertility. In rats, there were no adverse 
effects on male or female fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Maraviroc may have a minor influence on the ability to drive and use machines. Patients should be 
informed that dizziness has been reported during treatment with maraviroc. The clinical status of 
the patient and the adverse reaction profile of maraviroc should be borne in mind when considering 
the patient's ability to drive, cycle or operate machinery.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Adults 
Assessment of treatment related adverse reactions is based on pooled data from two Phase 2b/3 
studies in treatment-experienced adult patients (MOTIVATE 1 and MOTIVATE 2) and one study 
in treatment-naïve adult patients (MERIT) infected with CCR5-tropic HIV-1 (see sections 4.4 and 
5.1).  
 
The most frequently reported adverse reactions occurring in the Phase 2b/3 studies were nausea, 
diarrhoea, fatigue and headache. These adverse reactions were common (≥ 1/100 to < 1/10).  
 
Tabulated list of adverse reactions 
 
The adverse reactions are listed by system organ class (SOC) and frequency. Within each 
frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon 
(≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) , or not known (cannot be estimated from the 
available data).  The adverse reactions and laboratory abnormalities presented below are not 
exposure adjusted. 
 
Table 3: Adverse reactions observed in clinical trials or post-marketing  
 



 
 
 

41 
 

System Organ Class Adverse reaction Frequency 
Infections and infestations Pneumonia, oesophageal candidiasis uncommon 
Neoplasm benign, malignant and 
unspecified (including cysts and 
polyps) 

Bile duct cancer, diffuse large B-cell 
lymphoma, Hodgkin’s disease, 
metastases to bone, metastases to 
liver, metastases to peritoneum, 
nasopharyngeal cancer, oesophageal 
carcinoma 

rare 

Blood and lymphatic system 
disorders 

Anaemia common 
Pancytopenia, granulocytopenia rare 

Metabolism and nutrition disorders Anorexia common 
Psychiatric disorders Depression, insomnia common 
Nervous system disorders Seizures and seizure disorders uncommon 
Cardiac disorders Angina pectoris rare 
Vascular disorders Postural hypotension (see section 4.4) uncommon 
Gastrointestinal disorders Abdominal pain, flatulence, nausea  common 
Hepatobiliary disorders Alanine aminotransferase increased, 

aspartate aminotransferase increased 
common 

Hyperbilirubinaemia, gamma-
glutamyltransferase increased 

uncommon 

Hepatitis toxic, hepatic failure, 
hepatic cirrhosis, blood alkaline 
phosphatase increased 

rare 

Hepatic failure with allergic features very rare 
Skin and subcutaneous tissue 
disorders 

Rash common 
Stevens-Johnson syndrome / Toxic 
epidermal necrolysis 

rare / not known 

Musculoskeletal and connective 
tissue disorders 
 

Myositis, blood creatine 
phosphokinase increased 

uncommon 

Muscle atrophy rare 
Renal and urinary disorders Renal failure, proteinuria uncommon 
General disorders and 
administration site conditions 

Asthenia common 

 
 
Description of selected adverse reactions 
 
Delayed type hypersensitivity reactions, typically occurring within 2-6 weeks after start of therapy 
and including rash, fever, eosinophilia and liver reactions have been reported (see also section 4.4). 
Skin and liver reactions can occur as single events, or in combination. 
 
In HIV infected patients with severe immune deficiency at the time of initiation of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
infections may arise.  Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) 
have also been reported; however, the reported time to onset is more variable and these events can 
occur many months after initiation of treatment (see section 4.4). 
 
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged 
risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy 
(CART). The frequency of this is unknown (see section 4.4). 
 
Cases of syncope caused by postural hypotension have been reported. 
 
Laboratory abnormalities 



 
 
 

42 
 

 
Table 4 shows the incidence ≥1% of Grade 3-4 Abnormalities (ACTG Criteria) based on the 
maximum shift in laboratory test values without regard to baseline values. 
 
Table 4: Incidence ≥1% of grade 3-4 abnormalities (ACTG criteria) based on maximum shift 
in laboratory test values without regard to baseline studies MOTIVATE 1 and MOTIVATE 2 
(pooled analysis, up to 48 weeks) 
 

 
Laboratory parameter 

 
 

 
Limit 

Maraviroc 300 mg 
twice daily  

+ OBT 
N =421* 

(%) 

Placebo + OBT  
 

N =207* 
(%) 

Hepatobiliary disorders    
Aspartate aminotransferase >5.0x ULN 4.8 2.9 
Alanine aminotransferase >5.0x ULN 2.6 3.4 
Total bilirubin >5.0x ULN 5.5 5.3 
Gastrointestinal disorders    
Amylase >2.0x ULN 5.7 5.8 
Lipase >2.0x ULN 4.9 6.3 
Blood and lymphatic system disorders   
Absolute neutrophil count <750/mm3 4.3 1.9 

ULN: Upper Limit of Normal 
OBT: Optimised Background Therapy 
* Percentages based on total patients evaluated for each laboratory parameter 
 
The MOTIVATE studies were extended beyond 96 weeks, with an observational phase extended to 
5 years in order to assess the long term safety of maraviroc. The Long Term Safety/Selected 
Endpoints (LTS/SE) included death, AIDS-defining events, hepatic failure, Myocardial 
infarction/cardiac ischaemia, malignancies, rhabdomyolysis and other serious infectious events 
with maraviroc treatment.  The incidence of these selected endpoints for subjects on maraviroc in 
this observational phase was consistent with the incidence seen at earlier timepoints in the studies. 
 
In treatment-naïve patients, the incidence of grade 3 and 4 laboratory abnormalities using ACTG 
criteria was similar among the maraviroc and efavirenz treatment groups. 
 
Paediatric population 
 
The adverse reaction profile in paediatric patients is based on 48 Week safety data from study 
A4001031 in which 103 HIV-1 infected, treatment-experienced patients aged 2 to <18 years 
received maraviroc twice-daily with optimised background therapy (OBT).  Overall, the safety 
profile in paediatric patients was similar to that observed in adult clinical studies. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 
 
 

43 
 

The highest dose administered in clinical studies was 1,200 mg. The dose limiting adverse reaction 
was postural hypotension.  
 
Prolongation of the QT interval was seen in dogs and monkeys at plasma concentrations 6 and 12 
times, respectively, those expected in humans at the maximum recommended dose of 300 mg twice 
daily. However, no clinically significant QT prolongation compared to placebo + OBT was seen in 
the Phase 3 clinical studies using the recommended dose of maraviroc or in a specific 
pharmacokinetic study to evaluate the potential of maraviroc to prolong the QT interval.  
 
Management 
 
There is no specific antidote for overdose with maraviroc. Treatment of overdose should consist of 
general supportive measures including keeping the patient in a supine position, careful assessment 
of patient vital signs, blood pressure and ECG. 
 
If indicated, elimination of unabsorbed active maraviroc should be achieved by emesis or gastric 
lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed 
active substance. Since maraviroc is moderately protein bound, dialysis may be beneficial in 
removal of this medicine. Further management should be as recommended by the national poisons 
centre, where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, other antivirals, ATC code: J05AX09 
 
Mechanism of action 
 
Maraviroc is a member of a therapeutic class called CCR5 antagonists. Maraviroc selectively binds 
to the human chemokine receptor CCR5, preventing CCR5-tropic HIV-1 from entering cells. 
 
Antiviral activity in vitro 
 
Maraviroc has no antiviral activity in vitro against viruses which can use CXCR4 as their entry co-
receptor (dual-tropic or CXCR4-tropic viruses, collectively termed ‘CXCR4-using’ virus below). 
The serum adjusted EC90 value in 43 primary HIV-1 clinical isolates was 0.57 (0.06 – 10.7) ng/mL 
without significant changes between different subtypes tested. The antiviral activity of maraviroc 
against HIV-2 has not been evaluated. For details please refer to the pharmacology section of the 
CELSENTRI European Public Assessment Report (EPAR) on the European Medicines Agency 
(EMA) website. 
 
When used with other antiretroviral medicinal products in cell culture, the combination of 
maraviroc was not antagonistic with a range of NRTIs, NNRTIs, PIs or the HIV fusion inhibitor 
enfuvirtide.  
 
Virologic Escape 
 
Virologic escape from maraviroc can occur via 2 routes: the emergence of pre-existing virus which 
can use CXCR4 as its entry co-receptor (CXCR4-using virus) or the selection of virus that 
continues to use exclusively drug-bound CCR5 (CCR5-tropic virus).  
 
In vitro  
 



 
 
 

44 
 

HIV-1 variants with reduced susceptibility to maraviroc have been selected in vitro, following 
serial passage of two CCR5-tropic viruses (0 laboratory strains, 2 clinical isolates). The maraviroc-
resistant viruses remained CCR5-tropic and there was no conversion from a CCR5-tropic virus to a 
CXCR4-using virus.  
 
Phenotypic resistance 
 
Concentration response curves for the maraviroc-resistant viruses were characterized 
phenotypically by curves that did not reach 100% inhibition in assays using serial dilutions of 
maraviroc (<100% maximal percentage inhibition (MPI)). Traditional IC50/IC90 fold-change was 
not a useful parameter to measure phenotypic resistance, as those values were sometimes 
unchanged despite significantly reduced sensitivity. 
 
Genotypic resistance  
 
Mutations were found to accumulate in the gp120 envelope glycoprotein (the viral protein that 
binds to the CCR5 co-receptor). The position of these mutations was not consistent between 
different isolates. Hence, the relevance of these mutations to maraviroc susceptibility in other 
viruses is not known. 
 
Cross-resistance in vitro  
 
HIV-1 clinical isolates resistant to NRTIs, NNRTIs, PIs and enfuvirtide were all susceptible to 
maraviroc in cell culture. Maraviroc-resistant viruses that emerged in vitro remained sensitive to 
the fusion inhibitor enfuvirtide and the PI, saquinavir. 
 
In vivo 
 
Treatment-Experienced Adult Patients 
 
In the pivotal studies (MOTIVATE 1 and MOTIVATE 2), 7.6% of patients had a change in 
tropism result from CCR5-tropic to CXCR4-tropic or dual/mixed-tropic between screening and 
baseline (a period of 4-6 weeks).  
 
Failure with CXCR4-using virus 
 
CXCR4-using virus was detected at failure in approximately 60% of subjects who failed treatment 
on maraviroc, as compared to 6% of subjects who experienced treatment failure in the placebo + 
OBT arm. To investigate the likely origin of the on-treatment CXCR4-using virus, a detailed clonal 
analysis was conducted on virus from 20 representative subjects (16 subjects from the maraviroc 
arms and 4 subjects from the placebo + OBT arm) in whom CXCR4-using virus was detected at 
treatment failure. This analysis indicated that CXCR4-using virus emerged from a pre-existing 
CXCR4-using reservoir not detected at baseline, rather than from mutation of CCR5-tropic virus 
present at baseline. An analysis of tropism following failure of maraviroc therapy with CXCR4-
using virus in patients with CCR5 virus at baseline, demonstrated that the virus population reverted 
back to CCR5 tropism in 33 of 36 patients with more than 35 days of follow-up.  
 
At the time of failure with CXCR4-using virus, the resistance pattern to other antiretrovirals 
appears similar to that of the CCR5-tropic population at baseline, based on available data. Hence, 
in the selection of a treatment regimen, it should be assumed that viruses forming part of the 
previously undetected CXCR4 -using population (i.e. minor viral population) harbours the same 
resistance pattern as the CCR5-tropic population.  
 
Failure with CCR5-tropic virus 
 



 
 
 

45 
 

Phenotypic resistance  
 
In patients with CCR5-tropic virus at time of treatment failure with maraviroc, 22 out of 58 
patients had virus with reduced sensitivity to maraviroc. In the remaining 36 patients, there was no 
evidence of virus with reduced sensitivity as identified by exploratory virology analyses on a 
representative group. The latter group had markers correlating to low compliance (low and variable 
drug levels and often a calculated high residual sensitivity score of the OBT). In patients failing 
therapy with CCR5-tropic virus only, maraviroc might be considered still active if the MPI value is 
≥95% (PhenoSense Entry assay). Residual activity in vivo for viruses with MPI-values <95% has 
not been determined. 
 
Genotypic resistance 
  
A relatively small number of individuals receiving maraviroc-containing therapy have failed with 
phenotypic resistance (i.e. the ability to use drug-bound CCR5 with MPI <95%).   To date, no 
signature mutation(s) have been identified.  The gp120 amino acid substitutions identified so far 
are context dependent and inherently unpredictable with regards to maraviroc susceptibility.   
Treatment-Experienced Paediatric Patients 
 
In the Week 48 analysis (N=103), non-CCR5 tropic-virus was detected in 5/23 (22%) subjects at 
virologic failure. One additional subject had CCR5 tropic-virus with reduced susceptibility to 
maraviroc at virologic failure, although this was not retained at the end of treatment.  Subjects with 
virologic failure generally appeared to have low compliance to both maraviroc and the background 
antiretroviral elements of their regimens. Overall, the mechanisms of resistance to maraviroc 
observed in this treatment-experienced paediatric population were similar to those observed in 
adult populations. 
 
Clinical results 
 
Studies in Treatment-Experienced Adult Patients Infected with CCR5-tropic Virus 
 
The clinical efficacy of maraviroc (in combination with other antiretroviral medicinal products) on 
plasma HIV RNA levels and CD4+ cell counts have been investigated in two pivotal randomized, 
double blind, multicentre studies (MOTIVATE 1 and MOTIVATE 2, n=1076) in patients infected 
with CCR5 tropic HIV-1 as determined by the Monogram Trofile Assay. 
 
Patients who were eligible for these studies had prior exposure to at least 3 antiretroviral medicinal 
product classes [≥1 NRTIs, ≥1 NNRTIs, ≥2 PIs, and/or enfurvirtide] or documented resistance to at 
least one member of each class. Patients were randomised in a 2:2:1 ratio to maraviroc 300 mg 
(dose equivalence) once daily, twice daily or placebo in combination with an optimized 
background consisting of 3 to 6 antiretroviral medicinal products (excluding low-dose ritonavir). 
The OBT was selected on the basis of the subject’s prior treatment history and baseline genotypic 
and phenotypic viral resistance measurements.  
 



 
 
 

46 
 

Table 5: Demographic and baseline characteristics of patients (pooled studies MOTIVATE 1 
and MOTIVATE 2) 
 

 
Demographic and Baseline Characteristics 

Maraviroc 300 mg 
twice daily 

+ OBT 
 

N = 426 

Placebo + OBT  
 
 

N = 209 

Age (years) 
(Range, years) 

46.3 
21-73 

45.7 
29-72 

Male Sex 89.7% 88.5% 
Race (White/Black/Other) 85.2% / 12% / 2.8% 85.2% / 12.4% / 2.4% 
Mean Baseline HIV-1 RNA (log10 copies/mL) 4.85 4.86 
Median Baseline CD4+ Cell Count (cells/mm3)  
(range, cells/mm3) 

166.8 
(2.0-820.0) 

171.3 
(1.0-675.0) 

Screening Viral Load >100,000 copies/mL 179 (42.0%) 84 (40.2%) 
Baseline CD4+ Cell Count ≤200 cells/mm3 250 (58.7%) 118 (56.5%) 
Number (Percentage) of patients with GSS score1: 
 0 
 1 
 2 
 ≥3 

 
102 (23.9%) 
138 (32.4%) 
80 (18.8%) 

104 (24.4%) 

 
51 (24.4%) 
53 (25.4%) 
41 (19.6%) 
59 (28.2%) 

1Based on GeneSeq resistance assay  
 
Limited numbers of patients from ethnicities other than Caucasian were included in the pivotal 
clinical studies, therefore very limited data are available in these patient populations. 
 
The mean increase in CD4+ cell count from baseline in patients who failed with a change in 
tropism result to dual/mixed tropic or CXCR4, in the maraviroc 300 mg twice daily + OBT 
(+56 cells/mm3) group was greater than that seen in patients failing placebo + OBT 
(+13.8 cells/mm3) regardless of tropism. 
 
Table 6: Efficacy Outcomes at week 48 (pooled studies MOTIVATE 1 and MOTIVATE 2) 
 

Outcomes Maraviroc 300 mg 
twice daily 

+ OBT 
N=426 

Placebo + 
OBT  

 
N=209 

Difference1 
 (Confidence 

Interval2) 

HIV-1 RNA 
Mean change from baseline 
(log copies/mL) 

 
-1.837 

 

 
-0.785 

 
-1.055 

(-1.327, -0.783) 
Percentage of patients with 
HIV-1 RNA <400 copies/mL 

56.1% 
 

22.5% Odds ratio: 4.76 
(3.24, 7.00) 

Percentage of patients with 
HIV-1 RNA <50 copies/mL 

45.5% 
 

16.7% Odds ratio: 4.49 
(2.96, 6.83) 

CD4+ cell count 
Mean change from baseline 
(cells/µL) 

 
122.78 

 

59.17 
 

 
63.13 

(44.28, 81.99)2 
1 p-values < 0.0001 
2 For all efficacy endpoints the confidence intervals were 95%, except for HIV-1 RNA Change 
from baseline, which was 97.5% 
 
In a retrospective analysis of the MOTIVATE studies with a more sensitive assay for screening of 
tropism (Trofile ES), the response rates (<50 copies/mL at week 48) in patients with only CCR5-



 
 
 

47 
 

tropic virus detected at baseline was 48.2% in those treated with maraviroc + OBT (n=328), and 
16.3% in those treated with placebo + OBT (n=178). 
 
Maraviroc 300 mg twice daily + OBT was superior to placebo + OBT across all subgroups of 
patients analysed (see Table 7). Patients with very low CD4+ count at baseline (i.e. <50 cells/µL) 
had a less favourable outcome. This subgroup had a high degree of bad prognostic markers, i.e. 
extensive resistance and high baseline viral loads. However, a significant treatment benefit for 
maraviroc compared to placebo + OBT was still demonstrated (see Table 7). 
 
Table 7: Proportion of patients achieving <50 copies/mL at Week 48 by subgroup (pooled 
Studies MOTIVATE 1 and MOTIVATE 2) 
 

 
 

Subgroups 

HIV-1 RNA <50 copies/mL 
Maraviroc300 mg 
twice daily + OBT 

N=426 

Placebo + OBT 
 

N=209 
Screening HIV-1 RNA (copies/mL):  

<100,000 
≥100,000 

  
58.4% 
 34.7% 

 
 26.0% 
9.5% 

Baseline CD4+ (cells/µL):   
<50 
50-100 
101-200 
201-350 
≥ 350 

 
16.5% 
36.4% 
56.7% 
57.8% 
72.9% 

 
2.6% 

12.0% 
21.8% 
21.0% 
38.5% 

Number of active ARVs in OBT1: 
0  
1  
2  
≥3  

 
32.7% 
 44.5% 
 58.2% 
 62% 

 
2.0% 
 7.4% 
 31.7% 
 38.6% 

1Based on GSS. 
 
Studies in Treatment-Experienced Adult Patients Infected with Non-CCR5-tropic Virus  
 
Study A4001029 was an exploratory study in patients infected with dual/mixed or CXCR4 tropic 
HIV-1 with a similar design as the studies MOTIVATE 1 and MOTIVATE 2. Use of maraviroc 
was not associated with a significant decrease in HIV 1 RNA compared with placebo in these 
subjects and no adverse effect on CD4+ cell count was noted.  
Studies in Treatment-Naïve Adult Patients Infected with CCR5-tropic Virus  
 
A randomised, double-blinded study (MERIT), explored maraviroc versus efavirenz, both in 
combination with zidovudine/lamivudine (n=721, 1:1). After 48 weeks of treatment, maraviroc did 
not reach non-inferiority to efavirenz for the endpoint of HIV-1 RNA < 50 copies/mL (65.3 vs. 
69.3 % respectively, lower confidence bound -11.9%). More patients treated with maraviroc 
discontinued due to lack of efficacy (43 vs.15) and among patients with lack of efficacy, the 
proportion acquiring NRTI resistance (mainly lamivudine) was higher in the maraviroc arm. Fewer 
patients discontinued maraviroc due to adverse events (15 vs. 49). 
 
Studies in Adult Patients Co-infected with Hepatitis B and/or Hepatitis C virus  
 
The hepatic safety of maraviroc in combination with other antiretroviral agents in CCR5-tropic 
HIV-1-infected subjects with HIV RNA <50 copies/mL, co-infected with Hepatitis C and/or 
Hepatitis B Virus was evaluated in a multicentre, randomized, double blinded, placebo-controlled 
study. 70 subjects (Child-Pugh Class A, n=64; Child-Pugh Class B, n=6) were randomized to the 



 
 
 

48 
 

maraviroc group and 67 subjects (Child-Pugh Class A, n=59; Child-Pugh Class B, n=8) were 
randomized to the placebo group.  
 
The primary objective assessed the incidence of Grade 3 and 4 ALT abnormalities (>5x upper limit 
of normal (ULN) if baseline ALT ≤ ULN; or >3.5x baseline if baseline ALT > ULN) at Week 48. 
One subject in each treatment arm met the primary endpoint by Week 48 (at Week 8 for placebo 
and Week 36 for the maraviroc arm).  
 
Studies in Treatment-Experienced Paediatric Patients Infected with CCR5-tropic Virus 
 
Study A4001031 is an open-label, multicenter trial in paediatric patients (aged 2 years to less than 
18 years) infected with CCR5-tropic HIV-1, determined by the enhanced-sensitivity Trofile assay. 
Subjects were required to have HIV-1 RNA greater than 1,000 copies per mL at Screening.  
 
All subjects (n = 103) received maraviroc twice daily and OBT.  Maraviroc dosing was based on 
body surface area and doses were adjusted based on whether the subject was receiving potent 
CYP3A inhibitors and/or inducers. 
 
In paediatric patients with a successful tropism test, dual mixed/CXCR4-tropic virus was detected 
in around 40% of screening samples (8/27, 30% in 2-6 year-olds, 31/81, 38% in 6-12 year-olds and 
41/90, 46%  in 12-18 year-olds), underscoring the importance of tropism testing also in the 
paediatric population. 

 
The population was 52% female and 69% black, with mean age of 10 years (range: 2 years to 
17 years). At baseline, mean plasma HIV-1 RNA was 4.3 log10 copies/mL (range 2.4 to 6.2 log10 
copies per mL), mean CD4+ cell count was 551 cells/mm3 (range 1 to 1654 cells/mm3) and mean 
CD4+ % was 21% (range 0% to 42%).  
 
At 48 weeks, using a missing, switch or discontinuation equals failure analysis, 48% of subjects 
treated with maraviroc and OBT achieved plasma HIV-1 RNA less than 48 copies/mL and 65% of 
subjects achieved plasma HIV-1 RNA less than 400 copies per mL. The mean CD4+ cell count 
(percent) increase from baseline to Week 48 was 247 cells/mm3 (5%). 
 
5.2 Pharmacokinetic properties 
 
Absorption  
 
The absorption of maraviroc is variable with multiple peaks. Median peak maraviroc plasma 
concentrations are attained at 2 hours (range 0.5-4 hours) following single oral doses of 300 mg 
commercial tablet administered to healthy volunteers. The pharmacokinetics of oral maraviroc are 
not dose proportional over the dose range. The absolute bioavailability of a 100 mg dose is 23% 
and is predicted to be 33% at 300 mg. Maraviroc is a substrate for the efflux transporter P-
glycoprotein. 
 
Co-administration of a 300 mg tablet with a high fat breakfast reduced maraviroc Cmax and AUC by 
33% and co-administration of 75 mg of oral solution with a high fat breakfast reduced maraviroc 
AUC by 73% in adult healthy volunteers.  Studies with the tablets demonstrated a reduced food-
effect at higher doses.  
 
There were no food restrictions in the adult studies (using tablet formulations) or in the paediatric 
study (using both tablet and oral solution formulations). The results did not indicate any relevant 
efficacy or safety concern related to either fed or fasted dosing conditions. Therefore, maraviroc 
tablets and oral solution can be taken with or without food at the recommended doses in adults, 
adolescents and children aged 2 years and older and weighing at least 10 kg (see section 4.2). 
 



 
 
 

49 
 

Distribution 
 
Maraviroc is bound (approximately 76%) to human plasma proteins, and shows moderate affinity 
for albumin and alpha-1 acid glycoprotein. The volume of distribution of maraviroc is 
approximately 194 L.  
 
Biotransformation  
 
Studies in humans and in vitro studies using human liver microsomes and expressed enzymes have 
demonstrated that maraviroc is principally metabolized by the cytochrome P450 system to 
metabolites that are essentially inactive against HIV-1. In vitro studies indicate that CYP3A4 is the 
major enzyme responsible for maraviroc metabolism. In vitro studies also indicate that 
polymorphic enzymes CYP2C9, CYP2D6 and CYP2C19 do not contribute significantly to the 
metabolism of maraviroc.  
 
Maraviroc is the major circulating component (approximately 42% radioactivity) following a single 
oral dose of 300 mg. The most significant circulating metabolite in humans is a secondary amine 
(approximately 22% radioactivity) formed by N-dealkylation. This polar metabolite has no 
significant pharmacological activity. Other metabolites are products of mono-oxidation and are 
only minor components of plasma radioactivity. 
 
Elimination  
 
A mass balance/excretion study was conducted using a single 300 mg dose of 14C-labeled 
maraviroc. Approximately 20% of the radiolabel was recovered in the urine and 76% was 
recovered in the faeces over 168 hours. Maraviroc was the major component present in urine (mean 
of 8% dose) and faeces (mean of 25% dose). The remainder was excreted as metabolites. After 
intravenous administration (30 mg), the half-life of maraviroc was 13.2 h, 22% of the dose was 
excreted unchanged in the urine and the values of total clearance and renal clearance were 44.0 L/h 
and 10.17 L/h respectively. 
 
Special patient populations 
 
Paediatric population 
 
Intensive pharmacokinetics of maraviroc were evaluated in 50 treatment-experienced, CCR5-
tropic, HIV-1 infected paediatric patients aged 2 to 18 years (weight 10.0 to 57.6 kg) in the dose-
finding stage of clinical trial A4001031. Doses were given with food on intensive pharmacokinetic 
evaluation days and optimised to achieve an average concentration over the dosing interval (Cavg) 
of greater than 100 ng/mL; otherwise, maraviroc was given with or without food. The initial dose 
of maraviroc was scaled from adult doses using a body surface area (BSA) of 1.73 m2 to children 
and adolescent BSA (m2)-based bands. In addition, dosing was based on whether subjects were 
receiving potent CYP3A inhibitors (38/50), potent CYP3A inducers (2/50) or other concomitant 
medicinal products that are not potent CYP3A inhibitors or potent CYP3A inducers (10/50) as part 
of OBT. Sparse pharmacokinetics were evaluated in all subjects including the additional 47 
subjects receiving potent CYP3A inhibitors that did not take part in the dose-finding stage. The 
impact of potent CYP3A inhibitors and/or inducers on maraviroc pharmacokinetic parameters in 
paediatric patients was similar to that observed in adults. 
 
BSA (m2)-based bands have been modified to weight (kg)-based bands to simplify dosing and 
reduce dosing errors (see section 4.2).  Use of weight (kg)-based doses in treatment-experienced 
HIV-1-infected paediatrics results in maraviroc exposures similar to those observed in treatment-
experienced adults receiving recommended doses with concomitant medications.  The 
pharmacokinetics of maraviroc in paediatric patients below 2 years of age have not been 
established (see section 4.2). 
 



 
 
 

50 
 

Elderly 
 
Population analysis of the Phase 1/2a and Phase 3 studies (16-65 years of age) has been conducted 
and no effect of age has been observed (see section 4.2). 
  
Renal impairment 
 
A study compared the pharmacokinetics of a single 300 mg dose of maraviroc in subjects with 
severe renal impairment (CLcr < 30 mL/min, n=6) and end stage renal disease (ESRD) to healthy 
volunteers (n=6). The geometric mean AUCinf (CV%) for maraviroc was as follows: healthy 
volunteers (normal renal function) 1348.4 ng·h/mL (61%); severe renal impairment 4367.7 
ng·h/mL (52%); ESRD (dosing after dialysis) 2677.4 ng·h/mL (40%); and ESRD (dosing before 
dialysis) 2805.5 ng·h/mL (45%). The C max (CV%) was 335.6 ng/mL (87%) in healthy volunteers 
(normal renal function); 801.2 ng/mL (56%) in severe renal impairment; 576.7 ng/mL (51%) in 
ESRD (dosing after dialysis) and 478.5 ng/mL (38%) in ESRD (dosing before dialysis). Dialysis 
had a minimal effect on exposure in subjects with ESRD. Exposures observed in subjects with 
severe renal impairment and ESRD were within the range observed in single maraviroc 300 mg 
dose studies in healthy volunteers with normal renal function. Therefore, no dose adjustment is 
necessary in patients with renal impairment receiving maraviroc without a potent CYP3A4 
inhibitor (see sections 4.2, 4.4 and 4.5).  
 
In addition, the study compared the pharmacokinetics of multiple dose maraviroc in combination 
with saquinavir/ritonavir 1000/100 mg BID (a potent CYP3A4 inhibitor) for 7 days in subjects with 
mild renal impairment (CLcr >50 and ≤80 mL/min, n=6) and moderate renal impairment (CLcr 
≥30 and ≤50 mL/min, n=6) to healthy volunteers (n=6). Subjects received 150 mg of maraviroc at 
different dose frequencies (healthy volunteers – every 12 hours; mild renal impairment – every 24 
hours; moderate renal impairment – every 48 hours). The average concentration (Cavg) of 
maraviroc over 24 hours was 445.1 ng/mL, 338.3 ng/mL, and 223.7 ng/mL for subjects with 
normal renal function, mild renal impairment, and moderate renal impairment, respectively. The 
Cavg of maraviroc from 24-48 hours for subjects with moderate renal impairment was low (Cavg: 
32.8 ng/mL). Therefore, dosing frequencies of longer than 24 hours in subjects with renal 
impairment may result in inadequate exposures between 24-48 hours.  
 
Dose adjustment is necessary in patients with renal impairment receiving maraviroc with potent 
CYP3A4 inhibitors (see sections 4.2 and 4.4 and 4.5). 
 
Hepatic impairment  
 
Maraviroc is primarily metabolized and eliminated by the liver. A study compared the 
pharmacokinetics of a single 300 mg dose of maraviroc in patients with mild (Child-Pugh Class A, 
n=8), and moderate (Child-Pugh Class B, n=8) hepatic impairment compared to healthy subjects 
(n=8). Geometric mean ratios for Cmax and AUClast were 11% and 25% higher respectively for 
subjects with mild hepatic impairment, and 32% and 46% higher respectively for subjects with 
moderate hepatic impairment compared to subjects with normal hepatic function. The effects of 
moderate hepatic impairment may be underestimated due to limited data in patients with decreased 
metabolic capacity and higher renal clearance in these subjects. The results should therefore be 
interpreted with caution. The pharmacokinetics of maraviroc has not been studied in subjects with 
severe hepatic impairment (see sections 4.2 and 4.4).  
  
Race 
 
No relevant difference between Caucasian, Asian and Black subjects has been observed. The 
pharmacokinetics in other races has not been evaluated. 
 
Gender 
 



 
 
 

51 
 

No relevant differences in pharmacokinetics have been observed.  
 
Pharmacogenomics 
 
The pharmacokinetics of maraviroc is dependent on CYP3A5 activity and expression level, which 
can be modulated by genetic variation. Subjects with a functional CYP3A5 (CYP3A5*1 allele) 
have been shown to have a reduced exposure to maraviroc compared to subjects with defect 
CYP3A5 activity (e.g., CYP3A5*3, CYP3A5*6, and CYP3A5*7). The CYP3A5 allelic frequency 
depends on ethnicity: the majority of Caucasians (~90%) are poor metabolisers of CYP3A5 
substrates (i.e., subjects with no copy of functional CYP3A5 alleles) while approximately 40% of 
African-Americans and 70% of Sub-Saharan Africans are extensive metabolisers (i.e., subjects 
with two copies of functional CYP3A5 alleles). 
 
In a Phase 1 study conducted in healthy subjects, Blacks with a CYP3A5 genotype conferring 
extensive maraviroc metabolism (2 CYP3A5*1 alleles; n=12) had a 37% and 26% lower AUC 
when dosed with maraviroc 300 mg twice daily compared with Black (n=11) and Caucasian (n=12) 
subjects with CYP3A5 genotype conferring poor maraviroc metabolism (no CYP3A5*1 allele), 
respectively. The difference in maraviroc exposure between CYP3A5 extensive and poor 
metabolisers was reduced when maraviroc was administered together with a strong CYP3A 
inhibitor: extensive CYP3A5 metabolisers (n=12) had a 17% lower maraviroc AUC compared with 
poor CYP3A5 metabolisers (n=11) when dosed with maraviroc 150 mg once daily in the presence 
of darunavir/cobicistat (800/150 mg). 
 
All subjects in the Phase 1 study achieved the Cavg concentrations that have been shown to be 
associated with near maximal virologic efficacy with maraviroc (75 ng/mL) in the Phase 3 study in 
treatment-naïve adult patients (MERIT).  Therefore, despite differences in CYP3A5 genotype 
prevalence by race, the effect of CYP3A5 genotype on maraviroc exposure is not considered 
clinically significant and no maraviroc dose adjustment according to CYP3A5 genotype, race or 
ethnicity is needed. 
 
5.3 Preclinical safety data 
 
Primary pharmacological activity (CCR5 receptor affinity) was present in the monkey (100% 
receptor occupancy) and limited in the mouse, rat, rabbit and dog. In mice and human beings that 
lack CCR5 receptors through genetic deletion, no significant adverse consequences have been 
reported. 
 
In vitro and in vivo studies showed that maraviroc has a potential to increase QTc interval at 
supratherapeutic doses with no evidence of arrhythmia.  
 
Repeated dose toxicity studies in rats identified the liver as the primary target organ for toxicity 
(increases in transaminases, bile duct hyperplasia, and necrosis). 
 
Maraviroc was evaluated for carcinogenic potential by a 6 month transgenic mouse study and a 24 
month study in rats. In mice, no statistically significant increase in the incidence of tumours was 
reported at systemic exposures from 7 to 39-times the human exposure (unbound AUC 0-24h 
measurement) at a dose of 300 mg twice daily. In rats, administration of maraviroc at a systemic 
exposure 21-times the expected human exposure produced thyroid adenomas associated with 
adaptive liver changes. These findings are considered of low human relevance. In addition, 
cholangiocarcinomas (2/60 males at 900 mg/kg) and cholangioma (1/60 females at 500 mg/kg) 
were reported in the rat study at a systemic exposure at least 15-times the expected free human 
exposure. 
 
Maraviroc was not mutagenic or genotoxic in a battery of in vitro and in vivo assays including 
bacterial reverse mutation, chromosome aberrations in human lymphocytes and mouse bone 
marrow micronucleus.  



 
 
 

52 
 

 
Maraviroc did not impair mating or fertility of male or female rats, and did not affect sperm of 
treated male rats up to 1000 mg/kg. The exposure at this dose level corresponded to 39-fold the 
estimated free clinical AUC for a 300 mg twice daily dose.  
 
Embryofoetal development studies were conducted in rats and rabbits at doses up to 39- and 34-
fold the estimated free clinical AUC for a 300 mg twice daily dose. In rabbit, 7 foetuses had 
external anomalies at maternally toxic doses and 1 foetus at the mid dose of 75 mg/kg. 
 
Pre- and post-natal developmental studies were performed in rats at doses up to 27-fold the 
estimated free clinical AUC for a 300 mg twice daily dose. A slight increase in motor activity in 
high-dose male rats at both weaning and as adults was noted, while no effects were seen in females. 
Other developmental parameters of these offspring, including fertility and reproductive 
performance, were not affected by the maternal administration of maraviroc. 
 
 
6 PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Citric acid (anhydrous)  
Sodium citrate dihydrate 
Sucralose 
Sodium benzoate 
Strawberry flavouring  
Purified water 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
After first opening: 60 days 
 
6.4 Special precautions for storage 
 
Store below 30 ºC. Discard 60 days after first opening. The discard date of the oral solution should 
be written on the carton in the space provided. The date should be written as soon as the bottle has 
been opened for first use. 
 
6.5 Nature and contents of container 
 
High density polyethylene (HDPE) bottle, with a child resistant closure, containing 230 mL 
maraviroc 20 mg/mL solution. The pack also includes a thermoplastic elastomeric press in bottle 
adapter, and a 10 ml oral applicator comprised of a polypropylene barrel (with mL graduations) and 
a polyethylene plunger. 
 
The oral applicator is provided for accurate measurement of the prescribed dose of oral solution. 
 
6.6 Special precautions for disposal  
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 



 
 
 

53 
 

 
7 MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/418/013 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 18th September 2007 
Date of latest renewal: 20 July 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European 
Medicines Agency http://www.ema.europa.eu 
  



 
 
 

54 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



 
 
 

55 
 

A. MANUFACTURER (S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Tablets 
Pfizer Manufacturing Deutschland GmbH 
Betriebsstātte Freiburg  
Mooswaldallee 1 
79090 Freiburg 
Germany 
 
Oral solution 
Pfizer Service Company 
Hoge Wei 10 
B 1930 Zaventem 
Belgium 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
  
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Risk Management plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of  new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 
 
 

 
  



 
 
 

56 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 

  



 
 
 

57 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

  



 
 
 

58 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton for bottle containing 25 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 25 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 25 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
120 film-coated tablets 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 



 
 
 

59 
 

 
ViiV Healthcare BV  
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/011 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 25 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



 
 
 

60 
 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
Bottle label - 25 mg film-coated tablets  

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 25 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 25 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
120 film-coated tablets  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 



 
 
 

61 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV  
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/011 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 
  



 
 
 

62 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton for bottles containing 75 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 75 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 75 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
120 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 
 



 
 
 

63 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/012 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 75 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 

  



 
 
 

64 
 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
Bottle label - 75 mg film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 75 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 75 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
120 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 
 



 
 
 

65 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/012 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 

  



 
 
 

66 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton for bottles containing 150 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 150 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
180 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 
 



 
 
 

67 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/001 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 150 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



 
 
 

68 
 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
Bottle label - 150 mg film-coated tablets 

 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 150 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
180 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 
 



 
 
 

69 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/001 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 150 mg  
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



 
 
 

70 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton for bottles containing 300 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 300 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 300 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
180 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 
 



 
 
 

71 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/006 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 300 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



 
 
 

72 
 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
Bottle label - 300 mg film-coated tablets 
 

 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 300 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 300 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
180 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 



 
 
 

73 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/006 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 300 mg  
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



 
 
 

74 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton for blister pack containing 150 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 150 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
60 film-coated tablets 
90 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF  APPROPRIATE 



 
 
 

75 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
 
EU/1/07/418/002 
EU/1/07/418/003 
EU/1/07/418/004 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 150 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 

  



 
 
 

76 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
Carton for blister pack containing 300 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 300 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 300 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
60 film-coated tablets 
90 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 



 
 
 

77 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/007 
EU/1/07/418/008 
EU/1/07/418/009 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 300 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



 
 
 

78 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
  
Outer wrapper label on multi packs of 180 (2 packs of 90 film-coated tablets) wrapped in 
transparent foil - including the blue box - 150 mg film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Celsentri 150 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 180 (2 packs of 90) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 



 
 
 

79 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/005 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 150 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



 
 
 

80 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Outer wrapper label on multi packs of 180 (2 packs of 90 film-coated tablets) wrapped in 
transparent foil - including the blue box - 300 mg film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Celsentri 300 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 300 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 180 (2 packs of 90) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 



 
 
 

81 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/010 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 300 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



 
 
 

82 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
2x carton for blister pack containing 150 mg maraviroc film-coated tablets - without Blue Box 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Celsentri 150 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 film-coated tablets. Component of a multipack, cannot be sold seperately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 
 



 
 
 

83 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/005 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 150 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 
  



 
 
 

84 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
2x carton for blister pack containing 300 mg maraviroc film-coated tablets – without Blue Box 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Celsentri 300 mg film-coated tablets 
maraviroc 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 300 mg of maraviroc.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains soya lecithin: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 film-coated 
tablets. Component of a multipack, cannot be sold seperately.  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT  OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
9. SPECIAL STORAGE CONDITIONS 
  
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL 
PRODUCTS  OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL 
PRODUCTS, IF APPROPRIATE 



 
 
 

85 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/010 
 
 
13. BATCH NUMBER 
 
Lot {number}  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
celsentri 300 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 
  



 
 
 

86 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Blister Strip of 10 tablets of  150 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 150 mg film-coated tablets 
maraviroc 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare (logo) 
 
 
3. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
4. BATCH NUMBER 
 
Lot: {number}  
 
 
5. OTHER  
 
  



 
 
 

87 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Blister Strip of 10 tablets of  300 mg maraviroc film-coated tablets 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 300 mg film-coated tablets 
maraviroc 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare (logo) 
 
 
3. EXPIRY DATE 
 
EXP {MM-YYYY }  
 
 
4. BATCH NUMBER 
 
Lot: {number}  
 
 
5. OTHER  
 
  



 
 
 

88 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton for bottle containing 20 mg/ml maraviroc oral solution 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 20 mg/ml oral solution 
maraviroc 
 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of oral solution contains 20 mg maraviroc  
 
 

3. LIST OF EXCIPIENTS 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
Bottle contents: 
230 ml oral solution  
The pack contains an oral applicator and a bottle adapter. 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 

8. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
 

9. SPECIAL STORAGE CONDITIONS 
 
Store below 30 °C. 
Discard 60 days after first opening 
Discard by: 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 



 
 
 

89 
 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/013 
 
 

13. BATCH NUMBER 
 
Lot {number} 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 

15. INSTRUCTIONS ON USE 
 
 

16. INFORMATION IN BRAILLE 
 
celsentri 20 mg/ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



 
 
 

90 
 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
Bottle label – maraviroc 20 mg/ml oral solution 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
CELSENTRI 20 mg/ml oral solution 
maraviroc 
 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of oral solution contains 20 mg maraviroc 
 
 

3. LIST OF EXCIPIENTS 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
Bottle contents: 
230 ml oral solution  
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 

8. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
 

9. SPECIAL STORAGE CONDITIONS 
 
Store below 30 °C. 
Discard 60 days after first opening 
Discard by: 
 
 



 
 
 

91 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/07/418/013 
 
 

13. BATCH NUMBER 
 
Lot {number} 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 

15. INSTRUCTIONS ON USE 
 
 

16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 

 
 
  



 
 
 

92 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 

 
 



 
 
 

93 
 

Package leaflet: information for the user 
 

CELSENTRI 25 mg film-coated tablets 
CELSENTRI 75 mg film-coated tablets 

CELSENTRI 150 mg film-coated tablets 
CELSENTRI 300 mg film-coated tablets 

maraviroc 
 

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet.  See Section 4. 
 
What is in this leaflet:  
 
1. What CELSENTRI is and what it is used for 
2. What you need to know before you take CELSENTRI 
3. How to take CELSENTRI 
4. Possible side effects 
5. How to store CELSENTRI 
6. Contents of the pack and other information 
 
 
1. What CELSENTRI is and what it is used for 
 
CELSENTRI contains a medicine called maraviroc. Maraviroc belongs to a group of medicines 
called CCR5 antagonists. CELSENTRI works by blocking a receptor called CCR5 which HIV uses 
to enter and infect your blood cells. 
 
CELSENTRI is used to treat Human Immunodeficiency Virus type-1 (HIV-1) in adults, 
adolescents and children of 2 years and older, and weighing at least 10 kg. 
 
CELSENTRI must be taken in combination with other medicines which are also used to treat the 
HIV infection. These medicines are all called anti-HIV medicines or antiretrovirals. 
 
CELSENTRI, as part of combination therapy, reduces the amount of virus in your body, and keeps 
it at a low level. This helps your body to increase the CD4 cell count in your blood. CD4 cells are a 
type of white blood cell that are important in helping your body to fight infection. 
  
 
2 What you need to know before you take CELSENTRI 
 
Do not take CELSENTRI: 
• if you (or your child, if they are the patient) are allergic to maraviroc or to peanut or soya or to 

any of the other ingredients of CELSENTRI (listed in section 6 ). 

 Check with your doctor if you think this applies to you or your child. 
 



 
 
 

94 
 

Warnings and precautions 
 
Your doctor must take blood samples to test whether CELSENTRI is an appropriate treatment for 
you (or your child, if they are the patient). 
 
Some people taking CELSENTRI have developed serious allergic reactions or skin reactions (see 
also ‘Serious side effects’ in section 4). 
 
Before taking this medicine, make sure that your doctor knows if you (or your child) have or in the 
past had any of the following: 
 
• liver problems, including chronic hepatitis B or C. Only a limited number of people with liver 

problems have taken CELSENTRI. Your liver function may need to be closely monitored.  
(See also ‘Liver problems’ in section 4).       

• low blood pressure, including dizziness when you stand up or sit up quickly, or if you are 
taking any medicines to lower blood pressure. This is due to a sudden fall in blood pressure. If 
this happens, lie down until you (or your child) feel better. When getting up, do so as slowly as 
possible. 

• tuberculosis (TB) or serious fungal infections. CELSENTRI could potentially increase your 
risk of developing infections. 

• kidney problems. This is particularly important if you are also taking some other medicines 
(see ‘Other medicines and CELSENTRI’ later in section 2). 

 problems with your heart or circulatory system. Only a limited number of people with 
serious heart or circulatory problems have taken CELSENTRI. 

 Tell your doctor before starting treatment if you think any of these apply to you (or your 
child). 

 
Conditions you need to look out for 
 

Some people taking medicines for HIV infection develop other conditions, which can be serious. 
These include: 
 symptoms of infections and inflammation 
 joint pain, stiffness and bone problems 
 
You need to know about important signs and symptoms to look out for while you’re taking 
CELSENTRI. 

 Read the information ‘Other possible side effects of combination therapy for HIV’ in 
Section 4 of this leaflet. 

 
Protect other people 
HIV infection is spread by sexual contact with someone who has the infection, or by transfer of 
infected blood (for example, by sharing injection needles). You (or your child) can still pass on 
HIV when taking this medicine, although the risk is lowered by effective treatment. 

 Talk to your doctor about how to avoid infecting other people. 
 
Older people 
CELSENTRI has only been taken by limited numbers of people 65 years or older. If you belong to 
this age group, discuss with your doctor if you can use CELSENTRI. 
 
Children 



 
 
 

95 
 

The use of CELSENTRI has not been tested in children under the age of 2 or weighing less than 10 
kg . Therefore CELSENTRI is not recommended in children younger than 2, or weighing less than 
10 kg. 
 
Other medicines and CELSENTRI 
 
Tell your doctor or pharmacist if you (or your child) are taking, any other medicines, have 
recently taken, or might take any other medicines.  
 
Tell your doctor or pharmacist if you (or your child) begin taking a new medicine while  taking 
CELSENTRI. 
 
Medicines containing St. John’s Wort (Hypericum perforatum) are likely to prevent CELSENTRI 
from working properly. You should not take them while you’re taking CELSENTRI. 
 

Some medicines may change the amount of CELSENTRI in the body when they are taken at the 
same time as CELSENTRI. These include: 

• other medicines to treat HIV or hepatitis C infection (such as atazanavir, cobicistat, darunavir, 
efavirenz, etravirine, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, 
boceprevir, telaprevir) 

•  antibiotics (clarithromycin, telithromycin, rifampicin, rifabutin)  

• antifungal medicines (ketoconazole, itraconazole, fluconazole) 

• anticonvulsant medicines (carbamazepine, phenytoin, phenobarbital). 
 

 Tell your doctor if you (or your child) are taking any of these medicines. This will allow your 
doctor to prescribe the right dose of CELSENTRI.  

 
Pregnancy 
 
If you are pregnant, if you become pregnant, or if you are planning to have a baby: 

  Talk to your doctor about the risks and benefits of taking CELSENTRI. 
 

Breast-feeding 
 
Women who are HIV-positive must not breast-feed, because HIV infection can be passed on to 
the baby in breast milk.   

It is not known whether the ingredients in CELSENTRI can also pass into breast milk. If you are 
breast-feeding, or thinking about breast-feeding: 

 Talk to your doctor immediately. 
 
Driving and using machines 
 
CELSENTRI can make you dizzy. 

 Do not drive, cycle, or operate tools or machines unless you are sure you’re not affected. 
 
CELSENTRI contains soya lecithin. 
 
If you are allergic to peanut or soya do not use this medicinal product.  
 
 



 
 
 

96 
 

3. How to take CELSENTRI  
 
Always take or give this medicine exactly as your doctor has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
Your doctor will advise you whether it is better to take CELSENTRI oral solution, if you (or your 
child) are unable to swallow tablets. 
 
How much to take 
 
Adults 
The recommended dose of CELSENTRI is 150 mg, 300 mg or 600 mg twice per day depending 
on other medicines that you are taking at the same time. Always take the dose recommended by 
your doctor. 
 
People with kidney problems  
If you have a kidney problem, your doctor may alter your dose.  

 Talk to your doctor if this applies to you. 
 
Adolescents and children from 2 years of age and weighing at least 10 kg 
Your doctor will decide the correct dose of CELSENTRI based on weight and on other medicines 
being taken at the same time. 
 
CELSENTRI can be taken with or without food. CELSENTRI should always be taken by 
mouth.  
 
CELSENTRI must be taken in combination with other medicines to treat HIV. Refer to the 
Package Leaflets of these other medicines for guidance on how to take them.  
 
If you take or give more CELSENTRI than you should 
 
If you accidentally take or give too much CELSENTRI: 

 Contact your doctor or the nearest hospital immediately. 
 
If you forget to take or give CELSENTRI 
 
If you (or your child) miss a dose of CELSENTRI, take or give the missed dose as soon as possible 
and then continue with the next dose at its regular time.  
 
If it is almost time for the next dose, do not take or give the missed dose. Wait for the next dose at 
its regular time. 

Do not take or give a double dose to make up for a forgotten dose. 

 
If you or your child stop taking CELSENTRI 
 
Keep taking CELSENTRI until your doctor tells you to stop. 

Taking your medicines at the right time every day is important, as it makes sure the HIV infection 
does not increase in your body.  Therefore, unless your doctor tells you (or your child) to stop 
treatment, it is important to keep taking CELSENTRI correctly, as described above. 

 
If you have any further questions on the use of this medicine, ask your doctor or your pharmacist. 
 
 



 
 
 

97 
 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell 
your doctor if you notice anything unusual about your own health or your child’s health. 
 
 Serious side effects — get medical help immediately 
 
Serious allergic or skin reactions 
Some people taking CELSENTRI have developed severe and life-threatening skin reactions and 
allergic reactions. These are rare, and may affect up to 1 in 1,000 people taking CELSENTRI. 

If you get any of the following symptoms while you’re taking CELSENTRI : 
 swelling of the face, lips or tongue  
 difficulty breathing  
 widespread skin rash  
 fever (high temperature)  
 blisters and peeling skin, particularly around the mouth, nose, eyes and genitals. 
 Get medical help immediately if you get these symptoms. Stop taking CELSENTRI. 

 
Liver problems  

These are rare, and may affect up to 1 in 1,000 people taking CELSENTRI.  
Signs include:  
• loss of appetite  
• feeling sick or being sick 
• yellowing of skin or eyes 
• skin rash or itching 
• feeling very tired 
• stomach pain or tenderness 
• dark urine 
• drowsiness and confusion 
• fever (high temperature). 
 
 Contact a doctor immediately if you get these symptoms. Stop taking CELSENTRI. 

 
Other side effects 
 
Common side effects  

These may affect 1 to 10 in 100 people: 
• diarrhoea, feeling sick, stomach ache, wind (flatulence),  
• loss of appetite 
• headache,  problems sleeping,depression 
• rash (see also ‘Serious allergic or skin reactions’ earlier in section 4) 
•  feeling weak or lack of energy, anaemia (seen in blood test result) 
 increase in liver enzymes (seen in blood test results), which can be a sign of liver problems (see 

also ‘Liver problems’ earlier in section 4).  
 

Uncommon side effects 

These may affect up to 1 in 100 people:  
 lung infection 
 fungal infection of the gullet (oesophagus) 
 fits (seizures)  



 
 
 

98 
 

 feeling dizzy, faint or light headed when standing up 
 kidney failure, protein in the urine 
• an increase in a substance  known as CPK (seen in blood test results) which is a sign that 
 muscles are inflamed or damaged.  
 
Rare side effects 

These may affect up to 1 in 1,000 people: 
 chest pain (caused by reduced blood flow to the heart)  
 decrease in muscle size  
 some types of cancer, such as of the gullet (oesophagus) and bile duct  
 decrease in number of blood cells (seen in blood test results). 
 

 
Other possible side effects of combination therapy for HIV 

People taking combination therapy for HIV may get other side effects. 
 
Symptoms of infection and inflammation 

People with advanced HIV infection (AIDS) have weak immune systems, and are more likely to 
develop serious infections (opportunistic infections). When they start treatment, the immune 
system becomes stronger, so the body starts to fight infections. 

Symptoms of infection and inflammation may develop, caused by either: 
 old, hidden infections flaring up again as the body fights them 
 the immune system attacking healthy body tissue (autoimmune disorders). 

The symptoms of autoimmune disorders may develop many months after you start taking 
medicine to treat your HIV infection. Symptoms may include: 
 muscle weakness  
 weakness beginning in the hands and feet and moving up towards the trunk of the body  
 palpitations or tremor 
 hyperactivity (excessive restlessness and movement). 
If you get any symptoms of infection or if you notice any of the symptoms above: 

 Tell your doctor immediately. Don’t take other medicines for the infection without your 
doctor’s advice. 
 
Joint pain, stiffness and bone problems 

Some people taking combination therapy for HIV develop a condition called osteonecrosis. With 
this condition, parts of the bone tissue die because of reduced blood supply to the bone. 

It is not known how common this condition is. You may be more likely to develop it: 
 if you have been taking combination therapy for a long time 
 if you are also taking anti-inflammatory medicines called corticosteroids 
 if you drink alcohol 
 if you have a very weak immune system  
 if you are overweight. 

 
Signs to look out for include: 
 stiffness in the joints 
 aches and pains (especially in the hip, knee or shoulder) 
 difficulty moving. 



 
 
 

99 
 

If you notice any of these symptoms: 

 Tell your doctor. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet.  You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5.  How to store CELSENTRI 
 
Keep out of the sight and reach of children. 

 
Do not use CELSENTRI after the expiry date which is stated on the carton, blister or bottle label. 
The expiry date refers to the last day of that month. 

 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What CELSENTRI contains 
 
• The active ingredient in CELSENTRI is maraviroc. Each film-coated tablet contains 25 mg, 75 

mg, 150 mg or 300 mg of maraviroc. 
 
• The other ingredients are: 

 
Tablet core: cellulose microcrystalline, calcium hydrogen phosphate anhydrous, sodium 
starch glycolate, magnesium stearate 

 
Film-coat: poly (vinyl alcohol), titanium dioxide (E171), macrogol 3350, talc, soya lecithin, 
indigo carmine aluminium lake (E132). 

 
What CELSENTRI looks like and contents of the pack 
 
CELSENTRI film-coated tablets are blue coloured with “MVC 25”, “MVC 75”, “MVC 150” or 
“MVC 300”. 
 
CELSENTRI 25 mg and 75 mg film-coated tablets are supplied in bottles of 120 tablets. 
CELSENTRI 150 mg and 300 mg film-coated tablets are supplied in bottles of 180 tablets or in 
blister packs of 30, 60, 90 film-coated tablets and multipacks containing 180 (2 packs of 90) film-
coated tablets. 
 
Not all pack sizes may be marketed in all countries. 
 
 
Marketing Authorisation Holder 
 
ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 
 
 

100 
 

Manufacturer 
 
Pfizer Manufacturing Deutschland GmbH, Betriebsstātte Freiburg, Mooswaldallee 1, 79090 
Freiburg, Germany. 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
ViiV Healthcare srl/bv  
Tél/Tel: + 32 (0) 10 85 65 00 
 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България  
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
ViiV Healthcare srl/bv  
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 65 00 
 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 

 
Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
 dk-info@gsk.com 
 

 
Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 
 

Deutschland 
ViiV Healthcare GmbH  
Tel.: + 49 (0)89 203 0038-10  
viiv.med.info@viivhealthcare.com 
 

Nederland 
ViiV Healthcare BV  
Tel: + 31 (0)33 2081199 
 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
Laboratorios ViiV Healthcare, S.L.  
Tel: +34 900 923 501  
es-ci@viivhealthcare.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 
 

France 
ViiV Healthcare SAS  
Tél.: + 33 (0)1 39 17 6969 
Infomed@viivhealthcare.com 
 

Portugal 
VIIVHIV HEALTHCARE, UNIPESSOAL, LDA.  
Tel: + 351 21 094 08 01  
viiv.fi.pt@viivhealthcare.com 
 



 
 
 

101 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: + 385 1 6051 999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 
 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com  
 

Ísland 
Vistor hf. 
Sími: + 354 535 7000 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
ViiV Healthcare S.r.l. 
Tel: + 39 (0)45 9212611 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 
 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com  
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com  
 

United Kingdom 
ViiV Healthcare UK Ltd  
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  
 

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu/.  
  

mailto:gskcyprus@gsk.com
mailto:gskcyprus@gsk.com


 
 
 

102 
 

 
Package leaflet: information for the user 

 
CELSENTRI 20 mg /ml oral solution 

maraviroc 
 

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet.  See Section 4. 
 
What is in this leaflet:  
 
1. What CELSENTRI is and what it is used for 
2. What you need to know before you take CELSENTRI 
3. How to take CELSENTRI 
4. Possible side effects 
5. How to store CELSENTRI 
6. Contents of the pack and other information 
 
 
1. What CELSENTRI is and what it is used for 
 
CELSENTRI contains a medicine called maraviroc. Maraviroc belongs to a group of medicines 
called CCR5 antagonists. CELSENTRI works by blocking a receptor called CCR5 which HIV uses 
to enter and infect your blood cells. 
 
CELSENTRI is used to treat Human Immunodeficiency Virus type-1 (HIV-1) in adults, 
adolescents and children of 2 years and older, and weighing at least 10 kg. 
 
CELSENTRI must be taken in combination with other medicines which are also used to treat the 
HIV infection. These medicines are all called anti-HIV medicines or antiretrovirals. 
 
CELSENTRI, as part of combination therapy, reduces the amount of virus in your body, and keeps 
it at a low level. This helps your body to increase the CD4 cell count in your blood. CD4 cells are a 
type of white blood cell that are important in helping your body to fight infection. 
  
 
2 What you need to know before you take CELSENTRI 
 
Do not take CELSENTRI: 
• if you (or your child, if they are the patient) are allergic to maraviroc or to any of the other 

ingredients of CELSENTRI (listed in section 6 ). 

 Check with your doctor if you think this applies to you or your child. 
 
Warnings and precautions 
 
Your doctor must take blood samples to test whether CELSENTRI is an appropriate treatment for 
you (or your child, if they are the patient). 
 



 
 
 

103 
 

Some people taking CELSENTRI have developed serious allergic reactions or skin reactions (see 
also ‘Serious side effects’ in section 4). 
 
Before taking this medicine, make sure that your doctor knows if you (or your child) have or in the 
past had any of the following: 
 liver problems, including chronic hepatitis B or C. Only a limited number of people with liver 

problems have taken CELSENTRI. Your liver function may need to be closely monitored.  (See 
also ‘Liver problems’ in section 4). 

 low blood pressure, including dizziness when you stand up or sit up quickly, or if you are 
taking any medicines to lower blood pressure. This is due to a sudden fall in blood pressure. If 
this happens, lie down until you (or your child) feel better. When getting up, do so as slowly as 
possible. 

 tuberculosis (TB) or serious fungal infections. CELSENTRI could potentially increase your 
risk of developing infections. 

 kidney problems. This is particularly important if you are also taking some other medicines (see 
‘Other medicines and CELSENTRI’ later in section 2). 

 problems with your heart or circulatory system. Only a limited number of people with 
serious heart or circulatory problems have taken CELSENTRI. 

 Tell your doctor before starting treatment if you think any of these apply to you (or your 
child). 

 

Conditions you need to look out for 

Some people taking medicines for HIV infection develop other conditions, which can be serious. 
These include: 
 symptoms of infections and inflammation 
 joint pain, stiffness and bone problems. 
You need to know about important signs and symptoms to look out for while you’re taking 
CELSENTRI. 

 Read the information ‘Other possible side effects of combination therapy for HIV’ in 
Section 4 of this leaflet. 

 
Protect other people 
HIV infection is spread by sexual contact with someone who has the infection, or by transfer of 
infected blood (for example, by sharing injection needles). You (or your child) can still pass on 
HIV when taking this medicine, although the risk is lowered by effective treatment.  

 Talk to your doctor about how to avoid infecting other people. 
 
Older people 
CELSENTRI has only been taken by limited numbers of people 65 years or older. If you belong to 
this age group, discuss with your doctor if you can use CELSENTRI. 
 
Children 
CELSENTRI has not been tested in children under the age of 2 or weighing less than 10 kg. 
Therefore CELSENTRI is not recommended for children younger than 2 years, or weighing less 
than 10 kg. 
 
Other medicines and CELSENTRI 
 
Tell your doctor or pharmacist if you (or your child) are taking any other medicines,have 
recently taken, or might take any other medicines.  



 
 
 

104 
 

 
Tell your doctor or pharmacist if you (or your child) begin taking a new medicine while taking 
CELSENTRI. 
 
Medicines containing St. John’s Wort (Hypericum perforatum) are likely to prevent CELSENTRI 
from working properly. You should not take them while you’re taking CELSENTRI. 
 
Some medicines may change the amount of CELSENTRI in the body when they are taken at the 
same time as CELSENTRI. These include:  
 other medicines to treat HIV or hepatitis C infection (such as atazanavir, cobicistat, darunavir, 

efavirenz, etravirine, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, 
boceprevir, telaprevir) 

 antibiotics (clarithromycin, telithromycin, rifampicin, rifabutin) 
 antifungal medicines (ketoconazole, itraconazole, fluconazole) 
 anticonvulsant medicines (carbamazepine, phenytoin, phenobarbital). 
 

 Tell your doctor if you (or your child) are taking any of these medicines. This will allow your 
doctor to prescribe the right dose of CELSENTRI.  

 
Pregnancy 

If you are pregnant, if you become pregnant, or if you are planning to have a baby: 

 Talk to your doctor about the risks and benefits of taking CELSENTRI.  
 

Breast-feeding 
Women who are HIV-positive must not breast-feed, because HIV infection can be passed on to 
the baby in breast milk.  

It is not known whether the ingredients in CELSENTRI can also pass into breast milk. If you are 
breast-feeding, or thinking about breast-feeding: 

 Talk to your doctor immediately. 
 
Driving and using machines 
 
CELSENTRI can make you dizzy. 

 Don’t drive, cycle, or operate tools or machines unless you are sure you’re not affected. 
 
 
3. How to take CELSENTRI  
 
Always take or give this medicine exactly as your doctor has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
Your doctor will advise you whether it is better to take CELSENTRI oral solution, if you (or your 
child) are unable to swallow tablets. 
 
How much to take 
 
Adults 
The recommended dose of CELSENTRI is either 150 mg (7.5 ml), 300 mg (15 ml) or 600 mg 
(30 ml) twice daily, depending on other medicines that you are taking at the same time. Always 
take the dose recommended by your doctor. 



 
 
 

105 
 

 
People with kidney problems 
If you have a kidney problem, your doctor may alter your dose.  

 Talk to your doctor if this applies to you. 
 

Adolescents and children from 2 years of age and weighing at least 10 kg 
Your doctor will decide the correct dose of CELSENTRI, based on weight and on other medicines 
being taken at the same time.  

See the diagram and instructions at the end of this section for how to measure and take (or 
give) a dose of medicine. 
 
CELSENTRI can be taken with or without food. CELSENTRI should always be taken by 
mouth.  
 
CELSENTRI must be taken in combination with other medicines to treat HIV. Refer to the 
Package Leaflets of these other medicines for guidance on how to take them.  
 
If you take or give more CELSENTRI than you should 
 
If you accidentally take or give too much CELSENTRI: 

 Contact your doctor or the nearest hospital immediately.  
 
If you forget to take or give CELSENTRI 
 
If you (or your child) miss a dose of CELSENTRI, take or give the missed dose as soon as possible 
and then continue with the next dose at its regular time. 

If it is almost time for the next dose, do not take or give the missed dose. Wait for the next dose at 
its regular time. 

Do not take or give a double dose to make up for a forgotten dose. 
 
If you or your child stop taking CELSENTRI 
 
Keep taking CELSENTRI until your doctor tells you to stop.  

Taking your medicines at the right time every day is important as it makes sure the HIV infection 
does not increase in your body. Therefore, unless your doctor tells you (or your child) to stop 
treatment, it is important to keep taking CELSENTRI correctly, as described above.  
 
If you have any further questions on the use of this medicine, ask your doctor or your pharmacist. 
 



 
 
 

106 
 

How to measure the dose and take the medicine 

 
 
Use the oral applicator supplied with the pack to measure your dose accurately.  

1. Remove the bottle cap (A). Keep it safely 

2. Hold the bottle firmly. Push the plastic adapter (B) into the neck of the bottle so it is fully 
inserted.  

3. Insert the applicator (C) firmly into the adapter. 

4.  Turn the bottle upside down. 

5. Pull out applicator plunger (D) until the applicator contains the first part of the full dose.  

6. Turn the bottle the correct way up. Remove the applicator from the adapter. 

7. Put the applicator into your (or your child’s) mouth, placing the tip of the applicator against 
the inside of the cheek. Slowly push the plunger in, allowing time to swallow. Do not push too 
hard and squirt the liquid into the back of the throat, as that could cause choking.  

8. Repeat steps 3 to 7 in the same way until the whole dose has been taken. For example, if the 
dose is 15 ml, you need one and a half applicator -full of medicine. 

9. Remove and wash the applicator thoroughly in clean water once you have finished using it. Let 
it dry completely before you use it again. 

10. Close the bottle tightly with the cap, leaving the adaptor in place. 
 
Dispose of any unused oral solution 60 days after first opening the bottle. 
 
4. Possible side effects 
 



 
 
 

107 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell 
your doctor if you notice anything unusual about your own health or your child’s health. 
 
Serious side effects — get medical help immediately 
 
Serious allergic or skin reactions 

Some people taking CELSENTRI have developed severe and life-threatening skin reactions and 
allergic reactions. These are rare, and may affect up to 1 in 1,000 people taking CELSENTRI. 

If you get any of the following symptoms while you’re taking CELSENTRI : 
 swelling of the face, lips or tongue  
 difficulty breathing  
 widespread skin rash  
 fever (high temperature)  
 blisters and peeling skin, particularly around the mouth, nose, eyes and genitals. 
 Get medical help immediately if you get these symptoms. Stop taking CELSENTRI. 
 
Liver problems  

These are rare, and may affect up to 1 in 1,000 people taking CELSENTRI.  
Signs include:  
 loss of appetite  
 feeling sick or being sick 
 yellowing of skin or eyes 
 skin rash or itching 
 feeling very tired 
 stomach pain or tenderness 
 dark urine 
 drowsiness and confusion 
 fever (high temperature). 
 
 Contact a doctor immediately if you get these symptoms. Stop taking CELSENTRI. 
 
Other side effects 
 
Common side effects 

These may affect 1 to 10 in 100 people:  
• diarrhoea, feelingsick, stomach ache, wind (flatulence),  
• loss of appetite 
• headache, problems sleeping, depression 
• rash (see also ‘Serious allergic or skin reactions’ earlier in section 4) 
• feeling weak or lack of energy, anaemia (seen in blood test result) 
• increase in liver enzymes  (seen in blood test results), which can be a sign of liver problems (see 

also ‘Liver problems’ earlier in section 4).  
 
Uncommon side effects 

These may affect up to 1 in 100 people:  
 lung infection 
 fungal infection of the gullet (oesophagus) 



 
 
 

108 
 

 fits (seizures)  
 feeling dizzy, faint or light headed when standing up 
 kidney failure, protein in the urine 
• an increase in a substance  known as CPK (seen in blood test results) which is a sign that 
 muscles are inflamed or damaged.  
 
Rare side effects 

These may affect up to 1 in 1,000 people: 
 chest pain (caused by reduced blood flow to the heart)  
 decrease in muscle size  
 some types of cancer, such as of the gullet (oesophagus) and bile duct  
 decrease in number of blood cells (seen in blood test results). 
 
Other possible side effects of combination therapy for HIV 

People taking combination therapy for HIV may get other side effects. 
 
Symptoms of infection and inflammation 

People with advanced HIV infection (AIDS) have weak immune systems, and are more likely to 
develop serious infections (opportunistic infections). When they start treatment, the immune 
system becomes stronger, so the body starts to fight infections. 

Symptoms of infection and inflammation may develop, caused by either: 
 old, hidden infections flaring up again as the body fights them 
 the immune system attacking healthy body tissue (autoimmune disorders). 
The symptoms of autoimmune disorders may develop many months after you start taking 
medicine to treat your HIV infection. Symptoms may include: 
 muscle weakness  
 weakness beginning in the hands and feet and moving up towards the trunk of the body  
 palpitations or tremor 
 hyperactivity (excessive restlessness and movement). 
If you get any symptoms of infection or if you notice any of the symptoms above: 

 Tell your doctor immediately. Don’t take other medicines for the infection without your 
doctor’s advice. 
 
Joint pain, stiffness and bone problems 

Some people taking combination therapy for HIV develop a condition called osteonecrosis. With 
this condition, parts of the bone tissue die because of reduced blood supply to the bone.  
It is not known how common this condition is. You may be more likely to develop it: 
 if you have been taking combination therapy for a long time 
 if you are also taking anti-inflammatory medicines called corticosteroids 
 if you drink alcohol 
 if you have a very weak immune system  
 if you are overweight. 
 
Signs to look out for include: 
 stiffness in the joints 
 aches and pains (especially in the hip, knee or shoulder) 
 difficulty moving. 



 
 
 

109 
 

 
If you notice any of these symptoms: 

 Tell your doctor. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet.  You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5.  How to store CELSENTRI 
 
Keep out of the sight and reach of children. 

 
Do not use CELSENTRI after the expiry date which is stated on the bottle and carton label. The 
expiry date refers to the last day of that month. 

 
Store the oral solution below 30°C. 
Discard 60 days after first opening. Write the date the oral solution should be discarded on the 
carton in the space provided. The date should be written as soon as the bottle has been opened for 
first use. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What CELSENTRI contains 
 
• The active substance in CELSENTRI oral solution is 20 mg of maraviroc in each ml of the 

solution.  
 
• The other ingredients are: citric acid (anhydrous), sodium citrate dihydrate, sucralose, sodium 

benzoate, strawberry flavouring (501440T), purified water 
 

 
What CELSENTRI looks like and contents of the pack 
 
CELSENTRI oral solution is supplied in a carton containing a high density polyethylene bottle, 
with a child resistant cap. The solution is colourless with strawberry flavouring. The bottle contains 
230 ml of maraviroc solution (20 mg/ml). The pack includes an oral applicator and a bottle-adapter, 
which should be fitted in the bottle before use. 
 
 
Marketing Authorisation Holder 
 
ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands. 
 
Manufacturer 
 
Pfizer Service Company, Hoge Wei 10, B 1930 Zaventem, Belgium 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 
 
 

110 
 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
ViiV Healthcare srl/bv  
Tél/Tel: + 32 (0) 10 85 65 00 
 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България  
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
ViiV Healthcare srl/bv  
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 65 00 
 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 

 
Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
 dk-info@gsk.com 
 

 
Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 
 

Deutschland 
ViiV Healthcare GmbH  
Tel.: + 49 (0)89 203 0038-10  
viiv.med.info@viivhealthcare.com 
 

Nederland 
ViiV Healthcare BV  
Tel: + 31 (0)33 2081199 
 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
Laboratorios ViiV Healthcare, S.L.  
Tel: +34 900 923 501  
es-ci@viivhealthcare.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 
 

France 
ViiV Healthcare SAS  
Tél.: + 33 (0)1 39 17 6969 
Infomed@viivhealthcare.com 
 

Portugal 
VIIVHIV HEALTHCARE, UNIPESSOAL, LDA.  
Tel: + 351 21 094 08 01  
viiv.fi.pt@viivhealthcare.com 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: + 385 1 6051 999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 
 



 
 
 

111 
 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com  
 

Ísland 
Vistor hf. 
Sími: + 354 535 7000 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
ViiV Healthcare S.r.l. 
Tel: + 39 (0)45 9212611 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 
 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com  
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com  
 

United Kingdom 
ViiV Healthcare UK Ltd  
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  
 

 
 
This leaflet was last revised in 
 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu/.  
 
 
 
 

mailto:gskcyprus@gsk.com
mailto:gskcyprus@gsk.com

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER (S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET