Vocabria

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ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
400 mg 
 
Vocabria 400 mg prolonged-release suspension for injection 
 
600 mg 
 
Vocabria 600 mg prolonged-release suspension for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
400 mg 
 
Each vial contains 400 mg cabotegravir in 2 mL. 
 
600 mg 
 
Each vial contains 600 mg cabotegravir in 3 mL. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Prolonged-release suspension for injection. 
White to light pink suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Vocabria injection is indicated, in combination with rilpivirine injection, for the treatment of Human 
Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 
RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral 
resistance to, and no prior virological failure with agents of the NNRTI and INI class  (see sections 
4.2, 4.4 and 5.1). 
 
4.2 Posology and method of administration 
 
Vocabria should be prescribed by physicians experienced in the management of HIV infection. 
 
Each injection should be administered by a healthcare professional. 
 
Vocabria injection is indicated for the treatment of HIV-1 in combination with rilpivirine injection, 
therefore, the prescribing information for rilpivirine injection should be consulted for recommended 
dosing. 
 
Prior to starting Vocabria injection, healthcare professionals should have carefully selected 
patients who agree to the required injection schedule and counsel patients about the importance 



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of adherence to scheduled dosing visits to help maintain viral suppression and reduce the risk of 
viral rebound and potential development of resistance with missed doses. 
 
Following discontinuation of Vocabria and rilpivirine injection,  it is essential to adopt an 
alternative, fully suppressive antiretroviral regimen no later than one month after the final 
injection of Vocabria when dosed monthly and no later than two months after the final injection 
of Vocabria when dosed every 2 months (see section 4.4). 
 
Posology 
 
Adults 
 
Oral lead-in 
 
Prior to the initiation of Vocabria injection, oral cabotegravir together with oral rilpivirine should be 
taken for approximately one month (at least 28 days) to assess tolerability to cabotegravir and 
rilpivirine (see section 4.4). One cabotegravir 30 mg tablet should be taken with one rilpivirine 25 mg 
tablet, once daily. When administered with rilpivirine, cabotegravir tablets should be taken with a meal 
(see cabotegravir tablet prescribing information). 
 
Monthly dosing 
Initiation injection (600 mg corresponding to 3 mL dose) 
On the final day of oral lead in therapy, the recommended initial dose of Vocabria injection in adults is 
a single 600 mg intramuscular injection. Vocabria injection and rilpivirine injection should be 
administered at separate gluteal injection sites at the same visit. 
 
Continuation injection (400 mg corresponding to 2 mL dose) 
After the initiation injection, the continuation injection dose of Vocabria in adults is a single 400 mg 
monthly intramuscular injection. Vocabria injection and rilpivirine injection should be administered at 
separate gluteal injection sites at the same visit. Patients may be given injections up to 7 days before or 
after the date of the monthly 400 mg injection schedule. 
 
Table 1  Recommended oral lead-in and monthly intramuscular dosing schedule in adults 
  

ORAL LEAD IN INITIATION 
INJECTION 

CONTINUATION 
INJECTION 

Medicinal product During month 1 
(at least 28 days) 

At month 2  Month 3 onwards 

Vocabria 30 mg once daily 600 mg  400 mg monthly 

Rilpivirine 25 mg once daily 900 mg  600 mg monthly 

 



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Every 2 Month Dosing 
Initiation Injections – one month apart (600 mg) 
On the final day of oral lead-in therapy, the recommended initial Vocabria injection in adults is a 
single 600 mg intramuscular injection (month 2). 
 
One month later (month 3), a second Vocabria 600 mg intramuscular injection should be administered. 
Patients may be given the second 600 mg initiation injection up to 7 days before or after the scheduled 
dosing date.  
 
Vocabria injection and rilpivirine injection should be administered at separate gluteal injection sites at 
the same visit. 
 
Continuation Injections – 2 months apart (600 mg) 
After the initiation injections, the recommended Vocabria continuation injection dose in adults is a 
single 600 mg intramuscular injection (month 5) administered every 2 months. Vocabria injection and 
rilpivirine injection should be administered at separate gluteal injection sites at the same visit. Patients 
may be given injections up to 7 days before or after the date of the every 2 month, 600 mg injection 
schedule. 
 
Table 2  Recommended oral lead-in and every 2 month intramuscular dosing schedule in 
adults 
 

  ORAL LEAD-IN INITIATION 
INJECTIONS 
(one month apart)  

CONTINUATION 
INJECTIONS  
(two months apart) 

Drug During month 1 
(at least 28 days) 

At month 2 and 
month 3 

 Month 5 onwards 

Vocabria 30 mg once daily  600 mg 600 mg  

Rilpivirine 25 mg once daily 900 mg 900 mg 

 
Dosing recommendations when switching from monthly to every 2 month injections  
Patients switching from a monthly continuation injection schedule to an every 2 month continuation 
injection schedule should receive a single 600 mg intramuscular injection of cabotegravir one month 
after the last 400 mg continuation injection dose and then 600 mg every 2 months thereafter.  
 
Dosing recommendations when switching from every 2 month to monthly injections 
Patients switching from an every 2 month continuation injection schedule to a monthly continuation 
dosing schedule should receive a single 400 mg intramuscular injection of cabotegravir 2 months after 
the last 600 mg continuation injection dose and then 400 mg monthly thereafter. 
 
Missed doses 
Patients who miss a scheduled injection visit should be clinically reassessed to ensure resumption of 
therapy remains appropriate. See Table 3 for dosing recommendations after a missed injection. 
 
Missed monthly injection 
If a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (one 30 mg 
cabotegravir tablet and one 25 mg rilpivirine tablet once daily) may be used to replace up to 2 
consecutive monthly injection visits. For oral therapy durations greater than two months, an alternative 
oral regimen is recommended. 
 
The first dose of oral therapy should be taken one month (+/- 7 days) after the last injection doses of 
Vocabria and rilpivirine. Injection dosing should be resumed on the day oral dosing completes, as 
recommended in Table 3. 
 



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Table 3  Vocabria injection dosing recommendations after missed injections or oral 
therapy for patients on monthly injection dosing 

 
Time since last 
injection 

Recommendation 

≤2 months: Continue with the monthly 400 mg injection schedule as soon as 
possible  

>2 months: Re-initiate the patient on the 600 mg dose, and then continue to 
follow the monthly 400 mg injection schedule.  

 
Missed 2 month injection 
If a patient plans to miss a scheduled Vocabria injection visit by more than 7 days, oral therapy (one 30 
mg cabotegravir tablet and one 25 mg rilpivirine tablet, once daily) may be used to replace one, 2-
monthly injection visit. For oral therapy durations greater than two months, an alternative oral regimen 
is recommended. 
 
The first dose of oral therapy should be taken approximately two months (+/- 7 days) after the last 
injection doses of cabotegravir and rilpivirine. Injection dosing should be resumed on the day oral 
dosing completes, as recommended in Table 4. 
 
Table 4  Injection Dosing Recommendations After Missed Injections or Oral Therapy for 

patients on every 2 month injection dosing 
 

Missed Injection 
Visit  

Time since last 
injection 

Recommendation (all injections are 3 mL) 

Injection 2 
(Month 3) 

≤2 months Resume with 600 mg injection as soon as possible 
and then continue with the every 2 month injection 
schedule. 

>2 months Re-initiate the patient on the 600 mg dose, followed 
by a second 600 mg initiation injection one month 
later. Then follow the every 2 month injection 
schedule.  

Injection 3 or 
later (Month 5 
onwards) 

≤3 months Resume with 600 mg injection as soon as possible 
and then continue with the every 2 month injection 
schedule. 

>3 months Re-initiate the patient on the 600 mg dose, followed 
by a second 600 mg initiation injection one month 
later. Then follow the every 2 month injection 
schedule. 

 
Elderly 
No dose adjustment is required in elderly patients. There are limited data available on the use of 
cabotegravir in patients aged 65 years and over (see section 5.2). 
 
Renal impairment  
No dosage adjustment is required in patients with mild to severe renal impairment (CrCl <30 mL/min 
and not on dialysis [see section 5.2]). Cabotegravir has not been studied in patients with end-stage 
renal disease on renal replacement therapy. As cabotegravir is greater than 99% protein bound, dialysis 
is not expected to alter exposures of cabotegravir. If administered in a patient on renal replacement 
therapy, cabotegravir should be used with caution. 
 
Hepatic impairment 
No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh 
score A or B). Cabotegravir has not been studied in patients with severe hepatic impairment (Child-
Pugh score C, [see section 5.2]). If administered in a patient with severe hepatic impairment, 
cabotegravir should be used with caution. 



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Paediatric population 
The safety and efficacy of Vocabria in children and adolescents aged under 18 years have not been 
established. No data are available. 
 
Method of administration 
 
For intramuscular use. Care should be taken to avoid inadvertent injection into a blood vessel. 
 
Vocabria injection should be administered by a healthcare professional. For instructions on 
administration, see “Instructions for Use” in the package leaflet. 
 
Vocabria injection should always be co-administered with rilpivirine injection. The order of injections 
is not important. The prescribing information for rilpivirine injection should be consulted for 
recommended dosing. 
 
When administering Vocabria injection, healthcare professionals should take into consideration the 
Body Mass Index (BMI) of the patient to ensure that the needle length is sufficient to reach the gluteus 
muscle. 
 
Hold the vial firmly and vigorously shake for a full 10 seconds. Invert the vial and check the 
resuspension. It should look uniform. If the suspension is not uniform, shake the vial again. It is 
normal to see small air bubbles. 
 
Injections must be administered to the ventrogluteal (recommended) or the dorsogluteal sites. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Concomitant use with rifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin or 
phenobarbital (see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
Risk of resistance following treatment discontinuation 
 
To minimise the risk of developing viral resistance it is essential to adopt an alternative, fully 
suppressive antiretroviral regimen no later than one month after the final injection of Vocabria 
when dosed monthly and no later than two months after the final injection of Vocabria when 
dosed every 2 months. 
 
 
If virologic failure is suspected, an alternative regimen should be adopted as soon as possible. 
 
Long acting properties of Vocabria injection 
 
Residual concentrations of cabotegravir may remain in the systemic circulation of patients for 
prolonged periods (up to 12 months or longer), therefore, physicians should take the prolonged release 
characteristics of Vocabria injection into consideration when the medicinal product is discontinued 
(see sections 4.5, 4.6, 4.7 and 4.9). 
 
Baseline factors associated with virological failure 
 
Before starting the regimen, it should be taken into account that multivariable analyses indicate that a 
combination of at least 2 of the following baseline factors may be associated with an increased risk of 
virological failure: archived rilpivirine resistance mutations, HIV-1 subtype A6/A1, or 



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BMI ≥30 kg/m2. In patients with an incomplete or uncertain treatment history without pre-treatment 
resistance analyses, caution is warranted in the presence of either BMI ≥30 kg/m2 or HIV-1 A6/A1 
subtype (see section 5.1). 
 
Hypersensitivity reactions 
 
Hypersensitivity reactions have been reported in association with other integrase inhibitors. These 
reactions were characterised by rash, constitutional findings and sometimes organ dysfunction, 
including liver injury. While no such reactions have been observed to date in association with 
Vocabria, physicians should remain vigilant and should discontinue Vocabria and other suspected 
medicinal products immediately, should signs or symptoms of hypersensitivity develop (including, but 
not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint 
aches, blisters, oral lesions, conjunctivitis, facial oedema, hepatitis, eosinophilia or angioedema). 
Clinical status, including liver aminotransferases should be monitored and appropriate therapy 
initiated. Administration of oral lead-in is recommended to help identify patients who may be at risk of 
a hypersensitivity reaction (see section 4.2, and Long acting properties of Vocabria injection). 
 
Hepatoxicity 
 
Hepatotoxicity has been reported in a limited number of patients receiving Vocabria with or without 
known pre-existing hepatic disease (see section 4.8). 
Monitoring of liver chemistries is recommended and treatment with Vocabria should be discontinued 
if hepatotoxicity is suspected (see Long acting properties of Vocabria injection). 
 
HBV/HCV co-infection 
 
Patients with hepatitis B co-infection were excluded from studies with Vocabria. It is not 
recommended to initiate Vocabria in patients with hepatitis B co-infection. Physicians should refer to 
current treatment guidelines for the management of HIV infection in patients co-infected with hepatitis 
B virus. 
Limited data is available in patients with hepatitis C co-infection. Monitoring of liver function is 
recommended in patients with hepatitis C co-infection. 
 
Interactions with medicinal products 
 
Caution should be given to prescribing Vocabria injection with medicinal products that may reduce its 
exposure (see Section 4.5). 
 
Concomitant use of Vocabria injection with rifabutin is not recommended (see section 4.5). 
 
Transmission of HIV 
 
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. 
 
Immune reactivation 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 Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be evaluated and 
treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune 
hepatitis) have also been reported to occur in the setting of immune reconstitution, however, the 



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reported time to onset is more variable and these events can occur many months after initiation of 
treatment. 
 
Opportunistic infections 
 
Patients should be advised that Vocabria or any other antiretroviral therapy do not cure HIV infection 
and that they may still develop opportunistic infections and other complications of HIV infection. 
Therefore, patients should remain under close clinical observation by physicians experienced in the 
treatment of these associated HIV diseases. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Vocabria injection, in combination with rilpivirine injection, is indicated for the treatment of HIV-1, 
therefore, the prescribing information for rilpivirine injection should be consulted for associated 
interactions. 
 
Effect of other medicinal products on the pharmacokinetics of cabotegravir 
 
Cabotegravir is primarily metabolised by uridine diphosphate glucuronosyl transferase (UGT) 1A1 and 
to a lesser extent by UGT1A9. Medicinal products which are strong inducers of UGT1A1 or UGT1A9 
are expected to decrease cabotegravir plasma concentrations leading to lack of efficacy (see section 4.3 
and table 5 below). In poor metabolizers of UGT1A1, representing a maximum clinical UGT1A1 
inhibition, the mean AUC, Cmax and Ctau of oral cabotegravir increased by up to 1.5-fold. The impact 
of an UGT1A1 inhibitor may be slightly more pronounced, however, considering the safety margins of 
cabotegravir, this increase is not expected to be clinically relevant. No dosing adjustments for 
Vocabria are, therefore, recommended in the presence of UGT1A1 inhibitors (e.g. atazanavir, 
erlotinib, sorafenib). 
 
Cabotegravir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), 
however, because of its high permeability, no alteration in absorption is expected when co-
administered with either P-gp or BCRP inhibitors. 
 
Effect of cabotegravir on the pharmacokinetics of other medicinal products 
 
In vivo, cabotegravir did not have an effect on midazolam, a cytochrome P450 (CYP) 3A4 probe. In 
vitro, cabotegravir did not induce CYP1A2, CYP2B6, or CYP3A4. 
 
In vitro cabotegravir inhibited organic anion transporters (OAT) 1 (IC50=0.81 µM) and OAT3 
(IC50=0.41 µM). Therefore, caution is advised when co-dosing with narrow therapeutic index OAT1/3 
substrate drugs (e.g. methotrexate). 
 
Vocabria and rilpivirine injections are intended for use as a complete regimen for the treatment of 
HIV-1 infection and should not be administered with other antiretroviral medicinal products for the 
treatment of HIV. The following information regarding drug-drug interactions with other antiretroviral 
medicinal products is provided in the event that Vocabria and rilpivirine injections are stopped and 
initiation of an alternative antiviral therapy is necessary (see section 4.4). Based on the in vitro and 
clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-
retroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-
nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors or ibalizumab. 
 
No drug interaction studies have been performed with cabotegravir injection. The drug interaction data 
provided in Table 5 is obtained from studies with oral cabotegravir (increase is indicated as “↑”, 
decrease as “↓”, no change as “↔”, area under the concentration versus time curve as “AUC”, 
maximum observed concentration as “Cmax”, concentration at end of dosing interval as “Cτ”). 
 



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Table 5  Drug Interactions 
 

Medicinal products 
by therapeutic areas 

Interaction 
Geometric mean change (%) 

Recommendations concerning 
co-administration 

HIV-1 Antiviral medicinal products 
Non-nucleoside 
Reverse Transcriptase 
Inhibitor: 
Etravirine 

Cabotegravir ↔ 
AUC ↑ 1% 
Cmax ↑ 4% 
Cτ ↔ 0% 
 

Etravirine did not significantly change 
cabotegravir plasma concentration. No dose 
adjustment of Vocabria is necessary when 
initiating injections following etravirine use. 

Non-nucleoside 
Reverse Transcriptase 
Inhibitor: 
Rilpivirine 

Cabotegravir ↔ 
AUC ↑ 12% 
Cmax ↑ 5% 
Cτ ↑ 14% 
 
Rilpivirine ↔ 
AUC ↓ 1% 
Cmax ↓ 4% 
Cτ ↓ 8% 
 

Rilpivirine did not significantly change 
cabotegravir plasma concentration. No dose 
adjustment of Vocabria injection is necessary when 
co-administered with rilpivirine. 

Anticonvulsants 
Carbamazepine 
Oxcarbazepine 
Phenytoin 
Phenobarbital 

Cabotegravir ↓ Metabolic inducers may significantly decrease 
cabotegravir plasma concentration. Concomitant 
use is contraindicated (see section 4.3). 

Antimycobacterials 
Rifampicin 
 
 

Cabotegravir ↓ 
AUC ↓ 59% 
Cmax ↓ 6% 

Rifampicin significantly decreased cabotegravir 
plasma concentration which is likely to result in 
loss of therapeutic effect. Dosing recommendations 
for co-administration of Vocabria with rifampicin 
have not been established and co-administration of 
Vocabria with rifampicin is contraindicated (see 
section 4.3). 
 

Rifapentine Cabotegravir ↓ Rifapentine may significantly decrease 
cabotegravir plasma concentrations. Concomitant 
use is contraindicated (see section 4.3). 

Rifabutin 
 

Cabotegravir ↓ 
AUC ↓ 21% 
Cmax ↓ 17% 
Cτ ↓ 8% 

Rifabutin may decrease cabotegravir plasma 
concentration. Concomitant use should be avoided. 

Oral contraceptives 
Ethinyl estradiol (EE) 
and Levonorgestrel 
(LNG) 

EE ↔ 
AUC ↑ 2% 
Cmax ↓ 8% 
Cτ ↔ 0% 
 
LNG ↔ 
AUC ↑ 12% 
Cmax ↑ 5% 
Cτ ↑ 7% 

Cabotegravir did not significantly change ethinyl 
estradiol and levonorgestrel plasma concentrations 
to a clinically relevant extent. No dose adjustment 
of oral contraceptives is necessary when co-
administered with Vocabria. 

 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are a limited amount of data from the use of cabotegravir in pregnant women. The effect of 
Vocabria on human pregnancy is unknown. 
 
Cabotegravir was not teratogenic when studied in pregnant rats and rabbits but, exposures higher than 
the therapeutic dose showed reproductive toxicity in animals (see section 5.3). The relevance to human 
pregnancy is unknown. 
 
Vocabria injection is not recommended during pregnancy unless the expected benefit justifies the 
potential risk to the foetus. 
 
Cabotegravir has been detected in systemic circulation for up to 12 months or longer after an injection 
(see section 4.4). 
 
Breast-feeding 
 
It is expected that cabotegravir will be secreted into human milk based on animal data, although this 
has not been confirmed in humans. Cabotegravir may be present in human milk for up to 12 months or 
longer after the last cabotegravir injection. 
 
It is recommended that HIV infected women do not breast-feed their infants under any circumstances 
in order to avoid transmission of HIV. 
 
Fertility 
 
There are no data on the effects of cabotegravir on human male or female fertility. Animal studies 
indicate no effects of cabotegravir on male or female fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Patients should be informed that dizziness, fatigue and somnolence has been reported during treatment 
with Vocabria injection. The clinical status of the patient and the adverse reaction profile of Vocabria 
injection should be borne in mind when considering the patient’s ability to drive or operate machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reactions (ARs) from monthly dosing studies were injection site 
reactions (up to 84%), headache (up to 12%) and pyrexia4 (10%). 
The most frequently reported ARs from ATLAS-2M every 2 month dosing were injection site 
reactions (76%), headache (7%) and pyrexia4 (7%). 
 
Tabulated list of adverse reactions 
 
The ARs identified for cabotegravir or rilpivirine are listed in Table 6 by body system organ class and 
frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon 
(≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). 
 
Table 6 Tabulated summary of adverse reactions1 

 



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MedDRA System Organ 
Class (SOC) 

Frequency 
Category 

ARs for Vocabria + rilpivirine regimen 

Psychiatric disorders Common Depression 
Anxiety 
Abnormal dreams 
Insomnia 

Nervous system disorders Very common Headache 
Common  Dizziness 
Uncommon Somnolence 

Vasovagal reactions (in response to 
injections) 

Gastrointestinal disorders Common Nausea 
Vomiting 
Abdominal pain2 

Flatulence 
Diarrhoea 

Hepatobiliary Disorders Uncommon Hepatotoxicity 
Skin and subcutaneous tissue 
disorders 

Common Rash3 

Musculoskeletal and 
connective tissue disorders 

Common Myalgia 

General disorders and 
administrative site conditions 

Very common Injection site reactions (pain and discomfort, 
nodule, induration) 
Pyrexia4 

Common Injection site reactions (swelling, erythema, 
pruritus, bruising, warmth, haematoma) 
Fatigue 
Asthenia 
Malaise 

Uncommon Injection site reactions (cellulitis, abscess, 
anaesthesia, haemorrhage, discolouration) 

Investigations Common Weight increased 
Uncommon Transaminase increased 

Blood bilirubin increased 

1 The frequency of the identified ARs are based on all reported occurrences of the events and are not limited to 
those considered at least possibly related by the investigator. 
2 Abdominal pain includes the following grouped MedDRA preferred term: abdominal pain, upper abdominal 
pain. 
3 Rash includes the following grouped MedDRA preferred terms: rash, rash erythematous, rash generalised, rash 
macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic. 
4 Pyrexia includes the following grouped MedDRA preferred terms: feeling hot, body temperature increased. 
 
Description of selected adverse reactions 
 
Local injection site reactions (ISRs) 
Up to 1% of subjects discontinued treatment with Vocabria plus rilpivirine because of ISRs. When 
dosing monthly, up to 84% of subjects reported injection site reactions; out of 30393 injections, 6815 
ISRs were reported. When dosing every 2 months, 76% of patients reported injection site reactions; 
out of 8470 injections, 2507 ISRs were reported. 
 
The severity of reactions was generally mild (Grade 1, 70%-75% of subjects) or moderate (Grade 2, 
27%-36% of subjects). 3-4% of subjects experienced severe (Grade 3) ISRs. The median duration of 
overall ISR events was 3 days. The percentage of subjects reporting ISRs decreased over time. 
 
Weight increased 



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At the Week 48 time point, subjects in studies FLAIR and ATLAS, who received Vocabria plus 
rilpivirine gained a median of 1.5 kg in weight subjects continuing on their current antiretroviral 
therapy (CAR) gained a median of 1.0 kg (pooled analysis). In the individual studies FLAIR and 
ATLAS, the median weight gains in the Vocabria plus rilpivirine arms were 1.3 kg and 1.8 kg 
respectively, compared to 1.5 kg and 0.3 kg in the CAR arms. 
 
At the 48 week timepoint, in ATLAS-2M the median weight gain in both the monthly and 2-monthly 
Vocabria plus rilpivirine dosing arms was 1.0 kg. 
 
Changes in laboratory chemistries 
Small, non-progressive increases in total bilirubin (without clinical jaundice) were observed with 
treatment with Vocabria plus rilpivirine. These changes are not considered clinically relevant as they 
likely reflect competition between cabotegravir and unconjugated bilirubin for a common clearance 
pathway (UGT1A1). 
 
Elevated transaminases (ALT/AST) were observed in subjects receiving Vocabria plus rilpivirine 
during clinical studies. These elevations were primarily attributed to acute viral hepatitis. A few 
subjects on oral therapy had transaminase elevations attributed to suspected drug-related 
hepatotoxicity; these changes were reversible upon discontinuation of treatment (see section 4.4). 
 
Elevated lipases were observed during clinical trials with Vocabria plus rilpivirine; Grade 3 and 4 
lipase increases occurred at a higher incidence with Vocabria plus rilpivirine compared with CAR. 
These elevations were generally asymptomatic and did not lead to Vocabria plus rilpivirine 
discontinuation. One case of fatal pancreatitis with Grade 4 lipase and confounding factors (including 
history of pancreatitis) has been reported in study ATLAS-2M, for which causality to the injection 
regimen could not be ruled out. 
 
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 
 
There is no specific treatment for Vocabria overdose. If overdose occurs, the patient should be treated 
supportively with appropriate monitoring as necessary. 
 
Cabotegravir is known to be highly protein bound in plasma; therefore, dialysis is unlikely to be 
helpful in removal of medicinal product from the body. Management of overdose with Vocabria 
injection should take into consideration the prolonged exposure to the medicine following an injection. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiviral for systemic use, integrase inhibitor, ATC code: J05AJ04. 
 
Mechanism of action 
 
Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand 
transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV 
replication cycle. 
 
Pharmacodynamic effects 

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Antiviral activity in cell culture 
Cabotegravir exhibited antiviral activity against laboratory strains of wild-type HIV-1 with mean 
concentration of cabotegravir necessary to reduce viral replication by 50 percent (EC50) values of 
0.22 nM in peripheral blood mononuclear cells (PBMCs), 0.74 nM in 293T cells and 0.57 nM in MT-4 
cells. Cabotegravir demonstrated antiviral activity in cell culture against a panel of 24 HIV-1 clinical 
isolates (three in each group of M clades A, B, C, D, E, F, and G, and 3 in group O) with EC50 values 
ranging from 0.02 nM to 1.06 nM for HIV-1. Cabotegravir EC50 values against three HIV-2 clinical 
isolates ranged from 0.10 nM to 0.14 nM. No clinical data is available in patients with HIV-2. 
 
Antiviral Activity in combination with other medicinal products 
No medicines with inherent anti-HIV activity were antagonistic to cabotegravir’s antiretroviral activity 
(in vitro assessments were conducted in combination with rilpivirine, lamivudine, tenofovir and 
emtricitabine). 
 
Resistance in vitro 
Isolation from wild-type HIV-1 and activity against resistant strains: Viruses with >10-fold increase in 
cabotegravir EC50 were not observed during the 112-day passage of strain IIIB. The following 
integrase (IN) mutations emerged after passaging wild type HIV-1 (with T124A polymorphism) in the 
presence of cabotegravir: Q146L (fold-change [FC] range 1.3-4.6), S153Y (FC range 3.6-8.4), and 
I162M (FC = 2.8). As noted above, the detection of T124A is selection of a pre-existing minority 
variant that does not have differential susceptibility to cabotegravir. No amino acid substitutions in the 
integrase region were selected when passaging the wild-type HIV-1 NL-432 in the presence of 6.4 nM 
of cabotegravir through Day 56. 
 
Among the multiple mutants, the highest FC was observed with mutants containing Q148K or Q148R. 
E138K/Q148H resulted in a 0.92-fold decrease in susceptibility to cabotegravir but E138K/Q148R 
resulted in a 12-fold decrease in susceptibility and E138K/Q148K resulted in an 81-fold decrease in 
susceptibility to cabotegravir. G140C/Q148R and G140S/Q148R resulted in a 22- and 12-fold 
decrease in susceptibility to cabotegravir, respectively. While N155H did not alter susceptibility to 
cabotegravir, N155H/Q148R resulted in a 61-fold decrease in susceptibility to cabotegravir. Other 
multiple mutants, which resulted in a FC between 5 and 10, are: T66K/L74M (FC=6.3), 
G140S/Q148K (FC=5.6), G140S/Q148H (FC=6.1) and E92Q/N155H (FC=5.3). 
 
Resistance in vivo 
The number of subjects who met Confirmed Virologic Failure (CVF) criteria was low across the 
pooled FLAIR and ATLAS trials. In the pooled analysis, there were 7 CVFs on cabotegravir plus 
rilpivirine (7/591, 1.2%) and 7 CVFs on current antiretroviral regimen (7/591, 1.2%). The three CVFs 
on cabotegravir plus rilpivirine in FLAIR with resistance data had Subtype A1. In addition, 2 of the 3 
CVFs had treatment-emergent integrase inhibitor resistance associated substitution Q148R while one 
of the three had G140R with reduced phenotypic susceptibility to cabotegravir. All 3 CVFs carried one 
rilpivirine resistance-associated substitution: K101E, E138E/A/K/T or E138K, and two of the three 
showed reduced phenotypic susceptibility to rilpivirine. The 3 CVFs in ATLAS had subtype A, A1 
and AG. One of the three CVFs carried the INI resistance-associated substitution N155H at failure 
with reduced cabotegravir phenotype susceptibility. All three CVFs carried one rilpivirine resistance-
associated substitution at failure: E138A, E138E/K or E138K, and showed reduced phenotypic 
susceptibility to rilpivirine. In two of these three CVFs, the rilpivirine resistance-associated 
substitutions observed at failure were also observed at baseline in PBMC HIV-1 DNA. The seventh 
CVF (FLAIR) never received an injection. 
 
The substitutions associated with resistance to long-acting cabotegravir injection, observed in the 
pooled ATLAS and FLAIR trials were G140R (n=1), Q148R (n=2), and N155H (n=1). 
 
In the ATLAS-2M study 10 subjects met CVF criteria through Week 48: 8 subjects (1.5%) in the Q8W 
arm and 2 subjects (0.4%) in the Q4W arm. Eight subjects met CVF criteria at or before the Week 24 
timepoint. 
 



14 

At Baseline in the Q8W arm, 5 subjects had rilpivirine resistance-associated mutations of Y181Y/C + 
H221H/Y, Y188Y/F/H/L, Y188L, E138A or E138E/A and 1 subject contained cabotegravir resistance 
mutation, G140G/R (in addition to the above Y188Y/F/H/L rilpivirine resistance-associated mutation). 
At the suspected virologic failure (SVF) timepoint in the Q8W arm, 6 subjects had rilpivirine 
resistance-associated mutations with 2 subjects having an addition of K101E and 1 subject having an 
addition of E138E/K from Baseline to SVF timepoint. Rilpivirine FC was above the clinical cut-off for 
7 subjects and ranged from 2.4 to 15. Five of the 6 subjects with rilpivirine resistance-associated 
substitution, also had INSTI resistance-associated substitutions, N155H (n=2); Q148R; 
Q148Q/R+N155N/H (n=2). INSTI substitution, L74I, was seen in 4/7 subjects. The Integrase genotype 
and phenotype assay failed for one subject and cabotegravir phenotype was unavailable for another. 
FCs for the Q8W subjects ranged from 0.6 to 9.1 for cabotegravir, 0.8 to 2.2 for dolutegravir and 0.8 to 
1.7 for bictegravir. 
 
In the Q4W arm, neither subject had any rilpivirine or INSTI resistance-associated substitutions at 
Baseline. One subject had the NNRTI substitution, G190Q, in combination with the NNRTI 
polymorphism, V189I. At SVF timepoint, one subject had on-treatment rilpivirine resistance-
associated mutations, K101E + M230L and the other retained the G190Q + V189I NNRTI 
substitutions with the addition of V179V/I. Both subjects showed reduced phenotypic susceptibility to 
rilpivirine. Both subjects also had INSTI resistance-associated mutations, either Q148R + E138E/K or 
N155N/H at SVF and 1 subject had reduced susceptibility to cabotegravir. Neither subject had the 
INSTI substitution, L74I. FCs for the Q4W subjects were 1.8 and 4.6 for cabotegravir, 1.0 and 1.4 for 
dolutegravir and 1.1 and 1.5 for bictegravir. 
 
Clinical efficacy and safety 
 
The efficacy of Vocabria plus rilpivirine has been evaluated in two Phase III randomised, multicentre, 
active-controlled, parallel-arm, open-label, non-inferiority studies, FLAIR (study 201584) and ATLAS 
(study 201585). The primary analysis was conducted after all subjects completed their Week 48 visit 
or discontinued the study prematurely. 
 
Patients virologically suppressed (on prior dolutegravir based regimen for 20 weeks) 
In FLAIR, 629 HIV-1-infected, antiretroviral treatment (ART)-naive subjects received a dolutegravir 
integrase strand transfer inhibitor (INSTI) containing regimen for 20 weeks (either 
dolutegravir/abacavir/lamivudine or dolutegravir plus 2 other nucleoside reverse transcriptase 
inhibitors if subjects were HLA-B*5701 positive). Subjects who were virologically suppressed (HIV-1 
RNA <50 copies per mL, n=566) were then randomised (1:1) to receive either the Vocabria plus 
rilpivirine regimen or remain on the current antiretroviral (CAR) regimen. Subjects randomised to 
receive the Vocabria plus rilpivirine regimen, initiated treatment with oral lead-in dosing with one 30 
mg Vocabria tablet plus one 25 mg rilpivirine tablet, daily, for at least 4 weeks, followed by treatment 
with Vocabria injection (month 1: 600 mg injection, month 2 onwards: 400 mg injection) plus 
rilpivirine injection (month 1: 900 mg injection, month 2 onwards: 600 mg injection) every month for 
an additional 44 weeks. This study was extended to 96 weeks. 
 
Patients virologically suppressed (stable on prior ARV therapy for at least 6 months) 
In ATLAS, 616 HIV-1-infected, ART-experienced, virologically-suppressed (for at least 6 months) 
subjects (HIV-1 RNA <50 copies per mL) were randomised (1:1) and received either the Vocabria 
plus rilpivirine regimen or remained on the CAR regimen. Subjects randomised to receive the 
Vocabria plus rilpivirine regimen, initiated treatment with oral lead-in dosing with one 30 mg 
Vocabria tablet plus one 25 mg rilpivirine  tablet, daily for at least 4 weeks, followed by treatment 
with Vocabria injection (month 1: 600 mg injection, month 2 onwards: 400 mg injection) plus 
rilpivirine injection (month 1: 900 mg injection, month 2 onwards: 600 mg injection) every month for 
an additional 44 weeks. In ATLAS, 50%, 17%, and 33% of subjects received an NNRTI, PI, or INI 
(respectively) as their baseline third treatment medicine class prior to randomisation and this was 
similar between treatment arms.  
 
Pooled data 



15 

At baseline, in the pooled analysis, for the Vocabria plus rilpivirine arm, the median age of subjects 
was 38 years, 27% were female, 27% were non-white, 1% were ≥ 65 years and 7% had CD4+ cell 
count less than 350 cells per mm3; these characteristics were similar between treatment arms. 
 
The primary endpoint of both studies was the proportion of subjects with plasma HIV-1 RNA ≥50 
copies/mL at week 48 (snapshot algorithm for the ITT-E population). 
 
In a pooled analysis of the two pivotal studies, Vocabria plus rilpivirine was non-inferior to CAR on 
the proportion of subjects having plasma HIV-1 RNA ≥50 c/mL (1.9% and 1.7% respectively) at 
Week 48. The adjusted treatment difference between Vocabria plus rilpivirine and CAR (0.2; 95% CI: 
-1.4, 1.7) for the pooled analysis met the non-inferiority criterion (upper bound of the 95% CI below 
4%). 
 
The primary endpoint and other week 48 outcomes, including outcomes by key baseline factors, for 
FLAIR and ATLAS are shown in Tables 7 and 8. 
 
Table 7  Virologic outcomes of randomised treatment of FLAIR and ATLAS at 48 Weeks 

(Snapshot analysis) 
 

 FLAIR ATLAS Pooled Data 
 Vocabria 

+ RPV 
N=283 

CAR 
N=283 

Vocabria 
+ RPV 
N=308 

CAR 
N=308 

Vocabria 
+RPV 
N=591 

CAR 
N=591 

HIV-1 RNA≥50 
copies/mL† (%) 6 (2.1) 7 (2.5) 5 (1.6) 3 (1.0) 11 (1.9) 10 (1.7) 

Treatment 
Difference % 
(95% CI)*  

-0.4 (-2.8,2.1) 0.7 (-1.2, 2.5) 0.2 (-1.4, 1.7) 

HIV-1 RNA <50 
copies/mL (%) 

265 (93.6) 264 (93.3) 285 (92.5) 294 (95.5) 550 (93.1) 558 (94.4) 

Treatment 
Difference % 
(95% CI)* 

0.4 (-3.7, 4.5) 
 

-3.0 (-6.7, 0.7) -1.4 (-4.1, 1.4) 

No virologic data 
at Week 48 
window (%) 

12 (4.2) 12 (4.2) 18 (5.8) 11 (3.6) 30 (5.1) 23 (3.9) 

Reasons 
Discontinued 
study/study drug 
due to adverse 
event or death (%) 

8 (2.8) 2 (0.7) 11 (3.6) 5 (1.6) 19 (3.2) 7 (1.2) 

Discontinued 
study/study drug 
for other reasons 
(%) 

4 (1.4) 10 (3.5) 7 (2.3) 6 (1.9) 11 (1.9) 16 (2.7) 

Missing data during 
window but on 
study (%) 

0 0 0 0 0 0 

* Adjusted for baseline stratification factors. 
† Includes subjects who discontinued for lack of efficacy, discontinued while not supressed. 
N = Number of subjects in each treatment group, CI = confidence interval, CAR = current antiviral regimen. 
 
Table 8  Proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL at Week 48 for 

key baseline factors (Snapshot Outcomes). 
 

Baseline factors 

Pooled Data from FLAIR and ATLAS 
Vocabria+RPV 

N=591 
n/N (%) 

CAR 
N=591 

n/N (%) 



16 

Baseline CD4+ 
(cells/ mm3) 

<350  0/42 2/54 (3.7) 
≥350 to <500 5/120 (4.2) 0/117 
≥500 6/429 (1.4) 8 / 420 (1.9) 

Gender Male 6/429 (1.4) 9/423 (2.1) 
 Female 5/162 (3.1) 1/168 (0.6) 
Race White 9/430 (2.1) 7/408 (1.7) 

Black 
African/American 2/109 (1.8) 3/133 (2.3) 

 Asian/Other 0/52 0/48 
BMI <30 kg/m2 6/491 (1.2) 8/488 (1.6) 

≥30 kg/m2 5/100 (5.0) 2/103 (1.9) 
Age (years) <50 9/492 (1.8) 8/466 (1.7) 

≥50 2/99 (2.0) 2/125 (1.6) 
Baseline 
antiviral 
therapy at 
randomisation 

PI 1/51 (2.0) 0/54 
INI 6/385 (1.6) 9/382 (2.4) 

NNRTIs 4/155 (2.6) 1/155 (0.6) 

BMI= body mass index 
PI= Protease inhibitor 
INI= Integrase inhibitor 
NNRTI= non-nucleoside reverse transcriptase inhibitor 
In the FLAIR and ATLAS studies, treatment differences across baseline characteristics (CD4+ count, 
gender, race, BMI, age, baseline third medicine treatment class) were comparable. 
In the FLAIR study at 96 Weeks, the results remained consistent with the results at 48 Weeks. The 
proportion of subjects having plasma HIV-1 RNA ≥50 c/mL in Vocabria plus rilpivirine (n=283) and 
CAR (n=283) was 3.2% and 3.2% respectively (adjusted treatment difference between Vocabria plus 
rilpivirine and CAR [0.0; 95% CI: -2.9, 2.9]). The proportion of subjects having plasma HIV-1 RNA 
<50 c/mL in Vocabria plus rilpivirine and CAR was 87% and 89%, respectively (adjusted treatment 
difference between Vocabria plus rilpivirine and CAR [-2.8; 95% CI: -8.2, 2.5]). 
 
Every 2 month dosing 
Patients virologically suppressed (stable on prior ARV therapy for at least 6 months) 
The efficacy and safety of Vocabria injection given every 2 months, has been evaluated in one Phase 
IIIb randomised, multicentre, parallel-arm, open-label, non-inferiority study, ATLAS-2M (207966). 
The primary analysis was conducted after all subjects completed their Week 48 visit or discontinued 
the study prematurely. 
In ATLAS-2M, 1045 HIV-1 infected, ART experienced, virologically suppressed subjects were 
randomised (1:1) and received a Vocabria plus rilpivirine injection regimen administered either every 
2 months or monthly. Subjects initially on non-cabotegravir/rilpivirine treatment received oral lead-in 
treatment comprising one 30 mg Vocabria tablet plus one 25 mg rilpivirine tablet, daily, for at least 4 
weeks. Subjects randomised to monthly Vocabria injections (month 1: 600 mg injection, month 2 
onwards: 400 mg injection) and rilpivirine injections (month 1: 900 mg injection, month 2 onwards: 
600 mg injection) received treatment for an additional 44 weeks. Subjects randomised to every 2 
month Vocabria injections (600 mg injection at months 1, 2, 4 and every 2 months thereafter) and 
rilpivirine injections (900 mg injection at months 1, 2, 4 and every 2 months thereafter) received 
treatment for an additional 44 weeks. Prior to randomisation, 63%, 13% and 24% of subjects received 
Vocabria plus rilpivirine for 0 weeks, 1 to 24 weeks and >24 weeks, respectively. 
 
At baseline, the median age of subjects was 42 years, 27% were female, 27% were non-white, 4% 
were ≥ 65 years and 6% had a CD4+ cell count less than 350 cells per mm3; these characteristics were 
similar between the treatment arms. 



17 

The primary endpoint in ATLAS-2M was the proportion of subjects with a plasma HIV-1 RNA 
≥50 c/mL at Week 48 (snapshot algorithm for the ITT-E population).  
 
In ATLAS-2M, Vocabria and rilpivirine administered every 2 months was non-inferior to Vocabria 
and rilpivirine administered every month on the proportion of subjects having plasma HIV-1 RNA ≥50 
c/mL (1.7% and 1.0% respectively) at Week 48. The adjusted treatment difference between Vocabria 
and rilpivirine administered every 2 months and every month (0.8; 95% CI: -0.6, 2.2) met the non-
inferiority criterion (upper bound of the 95% CI below 4%). 
 
Table 9  Virologic outcomes of randomised treatment of ATLAS-2M at 48 Weeks 
(Snapshot analysis) 
 

 2 month Dosing (Q8W) Monthly Dosing (Q4W) 
 N=522 (%) N=523 (%) 
HIV-1 RNA≥50 copies/mL† (%) 9 (1.7) 5 (1.0) 
Treatment Difference % (95% 
CI)*  

0.8 (-0.6, 2.2) 
 

HIV-1 RNA <50 copies/mL (%) 492 (94.3) 489 (93.5) 
Treatment Difference % (95% CI)* 0.8 (-2.1, 3.7) 
No virologic data at week 48 
window 

21 (4.0) 29 (5.5) 

Reasons:  
Discontinued study due to AE or 
death (%) 

9 (1.7) 13 (2.5) 

Discontinued study for other 
reasons (%) 

12 (2.3) 16 (3.1) 

On study but missing data in 
window (%) 

0 0 

* Adjusted for baseline stratification factors. 
† Includes subjects who discontinued for lack of efficacy, discontinued while not suppressed. 
N = Number of subjects in each treatment group, CI = confidence interval, CAR = current antiviral regimen. 
 
Table 10 Proportion of subjects with Plasma HIV-1 RNA ≥50 copies/mL at Week 48 for 

key baseline factors (Snapshot Outcomes). 
 

Baseline factors Number of HIV-1 RNA ≥50 c/mL/Total 
Assessed (%) 
2 Month Dosing 
(Q8W) 

Monthly dosing 
(Q4W) 

Baseline CD4+ cell 
count (cells/mm3) 

<350 1/ 35 (2.9) 1/ 27 (3.7) 

350 to <500 1/ 96 (1.0) 0/ 89 

≥500 7/391 (1.8) 4/407 (1.0) 

Gender Male 4/385 (1.0) 5/380 (1.3) 

Female 5/137 (3.5) 0/143 

Race White 5/370 (1.4) 5/393 (1.3) 

Non-White 4/152 (2.6) 0/130 

Black/African 
American 

4/101 (4.0) 0/ 90 



18 

BMI= body mass index 
 
In the ATLAS-2M study, treatment differences on the primary endpoint across baseline characteristics 
(CD4+ lymphocyte count, gender, race, BMI, age and prior exposure to cabotegravir/rilpivirine) were 
not clinically meaningful. 
 
Post-hoc analysis  
Multivariable analyses of pooled phase 3 studies (ATLAS, FLAIR and ATLAS-2M), including data 
from 1039 HIV-infected adults with no prior exposure to Vocabria plus rilpivirine, examined the 
influence of baseline viral and participant characteristics, dosing regimen, and post-baseline plasma 
drug concentrations on confirmed virologic failure (CVF) using regression modelling with a variable 
selection procedure. Through Week 48 in these studies, 13/1039 (1.25%) participants had CVF while 
receiving cabotegravir and rilpivirine. 
  
Four covariates were significantly associated (P<0.05 for each adjusted odds ratio) with increased risk 
of CVF: rilpivirine resistance mutations at baseline identified by proviral DNA genotypic assay, HIV-
1 subtype A6/A1 (associated with integrase L74I polymorphism), rilpivirine trough concentration 4 
weeks following initial injection dose, body mass index of at least 30 kg/m2 (associated with 
cabotegravir pharmacokinetics). Other variables including Q4W or Q8W dosing, female gender, or 
other viral subtypes (non A6/A1) had no significant association with CVF. No baseline factor, when 
present in isolation, was predictive of virologic failure. However, a combination of at least 2 of the 
following baseline factors was associated with an increased risk of CVF: rilpivirine resistance 
mutations, HIV-1 subtype A6/A1, or BMI≥30 kg/m2 (see Table 11). 
 
Table 11 Week 48 outcomes by presence of key baseline factors of rilpivirine resistance 

associated mutations, Subtype A6/A11 and BMI ≥30 kg/m2 

 

Baseline Factors (number) Virologic Successes (%)2 Confirmed Virologic Failure 
(%)3 

0 694/732 (94.8) 3/732 (0.41) 
1 261/272 (96.0) 1/272 (0.37)4 

≥2 25/35 (71.4) 9/35 (25.7)5 

TOTAL 
(95% Confidence Interval) 

980/1039 (94.3) 
(92.74%, 95.65%) 

13/1039 (1.25) 
(0.67%, 2.13%) 

1 HIV-1 subtype A1 or A6 classification based on Los Alamos National Library panel from HIV Sequence 
database (June 2020) 
2Based on the FDA Snapshot algorithm of RNA <50 copies/mL.  

Non-
Black/African 
American 

5/421 (1.2) 5/421 (1.2) 

BMI <30 kg/m2 3/409 (0.7) 3/425 (0.7) 

≥30 kg/m2 6/113 (5.3) 2/98 (2.0) 

Age (years) <35 4/137 (2.9) 1/145 (0.7) 

35 to <50 3/242 (1.2) 2/239 (0.8) 

≥50 2/143 (1.4) 2/139 (1.4) 

Prior exposure 
CAB/RPV 

None 5/327 (1.5) 5/327 (1.5) 

1-24 weeks 3/69 (4.3) 0/68 

>24 weeks 1/126 (0.8) 0/128 



19 

3 Defined as two consecutive measurements of HIV RNA >200 copies/mL. 
4 Positive Predictive Value (PPV) <1%; Negative Predictive Value (NPV) 98%; sensitivity 8%; specificity 74% 
5 PPV 26%; NPV 99.6%; sensitivity 69%; specificity 97.5% 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Vocabria injection in one or more subsets of the paediatric population in the treatment of HIV-1 
infection. 
 
5.2 Pharmacokinetic properties 
 
Cabotegravir pharmacokinetics is similar between healthy and HIV-infected subjects. The PK 
variability of cabotegravir is moderate to high. In HIV-infected subjects participating in Phase III 
studies, between-subject CVb% for Ctau ranged from 39 to 48%. Higher between-subject variability 
ranging from 41% to 89% was observed with single dose administration of long-acting cabotegravir 
injection. 
 
Table 12. Pharmacokinetic parameters following cabotegravir orally once daily, and 

initiation, monthly and every 2 month continuation intramuscular injections 
 

Dosing Phase 
Dosage 

Regimen 

Geometric Mean (5th, 95th Percentile)a 
AUC(0-tau)

b 
(µ•h/mL) 

Cmax 
(µ/mL) 

Ctau 
(µ/mL) 

Oral lead-inc 30 mg  
once daily 

145 
(93.5, 224) 

8.0 
(5.3, 11.9) 

4.6 
(2.8, 7.5) 

Initial 
injectiond 

600 mg IM 
Initial Dose 

1,591 
(714, 3,245) 

8.0 
(5.3, 11.9) 

1.5 
(0.65, 2.9) 

Monthly 
injectione 

400 mg IM 
monthly 

2,415 
(1,494, 3,645) 

4.2 
(2.5, 6.5) 

2.8 
(1.7, 4.6) 

Every 2-
month 

injectione 

600 mg IM 
Every 2-month 

3,764 
(2431, 5857) 

4.0 
(2.3, 6.8) 

1.6 
(0.8, 3.0) 

a Pharmacokinetic (PK) parameter values were based on individual post-hoc estimates from population PK 
models for patients in FLAIR and ATLAS for the monthly regimen and in ATLAS-2M for the every 2 month 
regimen.  

b tau is dosing interval: 24 hours for oral administration; 1 month for IM injections of extended-release injectable 
suspension. 

c Oral lead-in pharmacokinetic parameter values represent steady-state. 
d Initial injection AUC(0-tau) and Cmax values primarily reflect values following oral dosing because the initial 

injection was administered on the same day as the last oral dose; however, the Ctau value at Week 4 reflects the 
initial injection. 

e  Monthly and every 2 month injection pharmacokinetic parameter values represent Week◦48 data. 
 
Absorption 
 
Cabotegravir injection exhibits absorption-limited (flip-flop) kinetics resulting from slow absorption 
from the gluteal muscle into the systemic circulation resulting in sustained plasma concentrations. 
Following a single intramuscular dose, plasma cabotegravir concentrations are detectable on the first 
day and gradually rise to reach maximum plasma concentration with a median Tmax of 7 days. 
Cabotegravir has been detected in plasma up to 52 weeks or longer after administration of a single 
injection. Pharmacokinetic steady-state is achieved by 44 weeks. 
Plasma cabotegravir exposure increases in proportion or slightly less than in proportion to dose 
following single and repeat IM injection of doses ranging from 100 to 800 mg. 
 
Distribution 
 



20 

Cabotegravir is highly bound (>99%) to human plasma proteins, based on in vitro data. Following 
administration of oral tablets, the mean apparent oral volume of distribution (Vz/F) in plasma was 
12.3 L. In humans, the estimate of plasma cabotegravir Vc/F was 5.27 L and Vp/F was 2.43 L. These 
volume estimates, along with the assumption of high bioavailability, suggest some distribution of 
cabotegravir to the extracellular space. 
 
Cabotegravir is present in the female and male genital tract. Median cervical and vaginal tissue:plasma 
ratios ranged from 0.16 to 0.28 and median rectal tissue:plasma ratios were ≤0.08 following a single 
400 mg intramuscular injection (IM) at 4, 8, and 12 weeks after dosing. 
 
Cabotegravir is present in cerebrospinal fluid (CSF). In HIV-infected subjects receiving a regimen of 
cabotegravir injection plus rilpivirine injection, the cabotegravir CSF to plasma concentration ratio 
[median (range)] (n=16) was 0.003(range: 0.002 to 0.004) one week following a steady-state long 
acting cabotegravir (Q4W or Q8W) injection. Consistent with therapeutic cabotegravir concentrations 
in the CSF, CSF HIV-1 RNA (n=16) was <50 c/mL in 100% and <2 c/mL in 15/16 (94%) of subjects. 
At the same time point, plasma HIV-1 RNA (n=18) was <50 c/mL in 100% and <2 c/mL in 12/18 
(66.7%) of subjects. 
 
In vitro, cabotegravir was not a substrate of organic anion transporting polypeptide (OATP) 1B1, 
OATP1B3 or organic cation transporter (OCT1). 
 
Biotransformation 
 
Cabotegravir is primarily metabolised by UGT1A1 with a minor UGT1A9 component. Cabotegravir is 
the predominant circulating compound in plasma, representing > 90% of plasma total radiocarbon. 
Following oral administration in humans, cabotegravir is primarily eliminated through metabolism; 
renal elimination of unchanged cabotegravir is low (<1% of the dose). Forty-seven percent of the total 
oral dose is excreted as unchanged cabotegravir in the faeces. It is unknown if all or part of this is due 
to unabsorbed drug or biliary excretion of the glucuronide conjugate, which can be further degraded to 
form the parent compound in the gut lumen. Cabotegravir was observed to be present in duodenal bile 
samples. The glucuronide metabolite was also present in some, but not all, of the duodenal bile 
samples. Twenty-seven percent of the total oral dose is excreted in the urine, primarily as a 
glucuronide metabolite (75% of urine radioactivity, 20% of total dose). 
 
Cabotegravir is not a clinically relevant inhibitor of the following enzymes and transporters: CYP1A2, 
CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A1, UGT1A3, 
UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B15, and UGT2B17, P-gp, BCRP, Bile salt 
export pump (BSEP), OCT1, OCT2, OATP1B1, OATP1B3, multidrug and toxin extrusion transporter 
(MATE) 1, MATE 2-K, multidrug resistance protein (MRP) 2 or MRP4. 
 
Elimination 
 
Cabotegravir mean apparent terminal phase half-life is absorption-rate limited and is estimated to be 
5.6 to 11.5 weeks after a single dose IM injection. The significantly longer apparent half-life compared 
to oral reflects elimination from the injection site into the systemic circulation. The apparent CL/F was 
0.151 L/h. 
 
Linearity/non-linearity 
 
Plasma CAB exposure increases in proportion or slightly less than in proportion to dose following 
single and repeat IM injection of doses ranging from 100 to 800 mg. 
 
Polymorphisms 
 
In a meta-analysis of healthy and HIV-infected subject trials, HIV-infected subjects with UGT1A1 
genotypes conferring poor cabotegravir metabolism had a 1.2-fold mean increase in steady-state 
cabotegravir AUC, Cmax, and Ctau following long acting injection administration compared with 



21 

subjects with genotypes associated with normal metabolism via UGT1A1. These differences are not 
considered clinically relevant. No dose adjustment is required in subjects with UGT1A1 
polymorphisms. 
 
Special patient populations 
 
Gender 
Population pharmacokinetic analyses revealed no clinically relevant effect of gender on the exposure 
of cabotegravir, therefore no dose adjustment is required on the basis of gender. 
 
Race 
Population pharmacokinetic analyses revealed no clinically relevant effect of race on the exposure of 
cabotegravir, therefore no dosage adjustment is required on the basis of race. 
 
Body Mass Index (BMI)  
Population pharmacokinetic analyses revealed no clinically relevant effect of BMI on the exposure of 
cabotegravir, therefore no dose adjustment is required on the basis of BMI. 
 
Elderly 
Population pharmacokinetic analysis of cabotegravir revealed no clinically relevant effect of age on 
cabotegravir exposure. Pharmacokinetic data for cabotegravir in subjects of >65 years old are limited. 
 
Renal impairment 
No clinically important pharmacokinetic differences between subjects with severe renal impairment 
(CrCL <30 mL/min and not on dialysis) and matching healthy subjects were observed. No dosage 
adjustment is necessary for patients with mild to severe renal impairment (not on dialysis). 
Cabotegravir has not been studied in patients on dialysis. 
 
Hepatic impairment 
No clinically important pharmacokinetic differences between subjects with moderate hepatic 
impairment and matching healthy subjects were observed. No dosage adjustment is necessary for 
patients with mild to moderate hepatic impairment (Child-Pugh Score A or B). The effect of severe 
hepatic impairment (Child-Pugh Score C) on the pharmacokinetics of cabotegravir has not been 
studied. 
 
5.3 Preclinical safety data 
 
Carcinogenesis and mutagenesis 
 
Cabotegravir was not mutagenic or clastogenic using in vitro tests in bacteria and cultured mammalian 
cells, and an in vivo rodent micronucleus assay. Cabotegravir was not carcinogenic in long term 
studies in the mouse and rat. 
 
Reproductive toxicology studies 
 
No effect on male or female fertility was observed in rats treated with cabotegravir at oral doses up to 
1,000 mg/kg/day (>20 times the exposure in humans at the maximum recommended dose). 
 
In an embryo-foetal development study there were no adverse developmental outcomes following oral 
administration of cabotegravir to pregnant rabbits up to a maternal toxic dose of 2,000 mg/kg/day 
(0.66 times the exposure in humans at the MRHD) or to pregnant rats at doses up to 1,000 mg/kg/day 
(>30 times the exposure in humans at the MRHD). In rats, alterations in foetal growth (decreased body 
weights) were observed at 1,000 mg/kg/day. Studies in pregnant rats showed that cabotegravir crosses 
the placenta and can be detected in foetal tissue. 
 
In rat pre- and post-natal (PPN) studies cabotegravir reproducibly induced a delayed onset of 
parturition, and an increase in the number of stillbirths and neonatal mortalities at 1,000 mg/kg/day 



22 

(>30 times the exposure in humans at the MRHD). A lower dose of 5 mg/kg/day (approximately 10 
times the exposure in humans at the MRHD) cabotegravir was not associated with delayed parturition 
or neonatal mortality. In rabbit and rat studies there was no effect on survival when foetuses were 
delivered by caesarean section. Given the exposure ratio, the relevance to humans is unknown. 
 
Repeated dose toxicity 
 
The effect of prolonged daily treatment with high doses of cabotegravir has been evaluated in repeat 
oral dose toxicity studies in rats (26 weeks) and in monkeys (39 weeks). There were no drug-related 
adverse effects in rats or monkeys given cabotegravir orally at doses up to 1,000 mg/kg/day or 
500 mg/kg/day, respectively. 
 
In a 14 day and 28 day monkey toxicity study, gastro-intestinal (GI) effects (body weight loss, emesis, 
loose/watery faeces, and moderate to severe dehydration) were observed and were the result of local 
drug administration and not systemic toxicity. 
 
In a 3 month study in rats, when cabotegravir was administered by monthly sub-cutaneous (SC) 
injection (up to 100 mg/kg/dose); monthly IM injection (up to 75 mg/kg/dose) or weekly SC injection 
(100 mg/kg/dose), there were no adverse effects noted and no new target organ toxicities (at exposures 
>30 times the exposure in humans at the MRHD of 400 mg IM dose). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol (E421) 
Polysorbate 20 (E432) 
Macrogol (E1521) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
Unopened vial 
2 years 
 
Shelf life of suspension in syringe 
 
Chemical and physical in-use stability has been demonstrated for 2 hours at 25°C. 
Once the suspension has been drawn into the syringe, from a microbiological point of view, the 
product should be used immediately. If not used immediately, in-use storage times and conditions 
prior to use are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Unopened vial 
 
This medicinal product does not require any special storage conditions. 
Do not freeze. 
 
Suspension in syringe 
 



23 

For storage conditions after first opening of the product, see section 6.3. 
 
6.5 Nature and contents of container and special equipment for use, administration 
 
400 mg (2 mL vial) 
 
Brown 2 mL type I glass vial, with bromobutyl rubber stopper and a grey aluminium overseal with a 
dark grey plastic flip-cap. 
 
Each pack contains: 1 vial (400 mg), 1 graduated syringe (sterile, single use with volumetric markings 
every 0.2 mL), 1 vial adaptor and 1 injection needle (0.65 mm, 38 mm [23 gauge, 1½ inch]). 
 
600 mg (3mL vial) 
 
Brown 3 mL type I glass vial, with bromobutyl rubber stopper and a grey aluminium overseal with an 
orange plastic flip-cap.  
 
600 mg (3 mL) pack 
Each pack contains: 1 vial (600 mg), 1 graduated syringe (sterile, single use with volumetric markings 
every 0.2 mL), 1 vial adaptor and 1 injection needle (0.65 mm, 38 mm [23 gauge, 1½ inch]). 
 
6.6 Special precautions for disposal and other handling 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
Full instructions for use and handling of Vocabria injection are provided in the package leaflet (see 
Instructions for Use). 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H,  
3811 LP Amersfoort  
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1481/002 
EU/1/20/1481/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  
 
 
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. 
 

http://www.ema.europa.eu/


24 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vocabria 30 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains cabotegravir sodium equivalent to 30 mg cabotegravir. 
 
Excipient with known effect 
 
Each film-coated tablet contains 155 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
White, oval, film-coated tablets (approximately 8.0 mm by 14.3 mm), debossed with ‘SV CTV’ on one 
side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Vocabria tablets are indicated in combination with rilpivirine tablets for the short-term treatment of 
Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed 
(HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of 
viral resistance to, and no prior virological failure with agents of the NNRTI and INI class (see 
sections 4.2, 4.4 and 5.1) for: 

• oral lead in to assess tolerability of Vocabria and rilpivirine prior to administration of long 
acting cabotegravir injection plus long acting rilpivirine injection. 

• oral therapy for adults who will miss planned dosing with cabotegravir injection plus 
rilpivirine injection. 

 
4.2 Posology and method of administration 
 
Vocabria should be prescribed by physicians experienced in the management of HIV infection. 
 
Vocabria tablets are indicated for the short-term treatment of HIV in combination with rilpivirine 
tablets, therefore, the prescribing information for rilpivirine tablets should be consulted for 
recommended dosing. 
 
Prior to starting Vocabria, healthcare professionals should carefully select patients who agree to 
the required monthly injection schedule and counsel patients about the importance of adherence 
to scheduled dosing visits to help maintain viral suppression and reduce the risk of viral rebound 
and potential development of resistance with missed doses (see section 4.4). 
 



25 

Posology 
 
Adults 
 
Oral lead in 
Prior to the initiation of cabotegravir injection, Vocabria tablets together with rilpivirine tablets should 
be taken for approximately one month (at least 28 days) to assess tolerability to cabotegravir and 
rilpivirine (see section 4.4). One Vocabria 30 mg tablet should be taken with one rilpivirine 25 mg 
tablet, once daily. 
 
Table 1  Recommended Dosing Schedule in Adult Patients 
 
  ORAL LEAD IN 

Medicinal Product During month 1 

Vocabria 30 mg once daily 
Rilpivirine 25 mg once daily 

 
Oral dosing for missed injections of cabotegravir 
If a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (one Vocabria 
30 mg tablet and one rilpivirine 25 mg tablet once daily) may be used to replace up to 2 consecutive 
monthly injection visits or one, every 2 month injection visit. For oral therapy durations greater than 
two months, an alternative oral regimen is recommended. 
 
The first dose of oral therapy should be taken one month (+/- 7 days) after the last injection doses of 
cabotegravir and rilpivirine for patients being given monthly injections. For patients being given every 
2-month injections, the first dose of oral therapy should be taken 2 months (+/- 7 days) after the last 
injection doses of cabotegravir and rilpivirine. Injection dosing should be resumed on the day oral 
dosing completes. 
 
Missed doses 
If the patient misses a dose of Vocabria tablets, the patient should take the missed dose as soon as 
possible, providing the next dose is not due within 12 hours. If the next dose is due within 12 hours, 
the patient should not take the missed dose and simply resume the usual dosing schedule. 
 
If a patient vomits within 4 hours of taking Vocabria tablets, another Vocabria tablet should be taken. 
If a patient vomits more than 4 hours after taking Vocabria tablets, the patient does not need to take 
another dose of Vocabria until the next regular scheduled dose. 
 
Elderly 
No dose adjustment is required in elderly patients. There are limited data available on the use of 
cabotegravir in patients aged 65 years and over (see section 5.2). 
 
Renal impairment  
No dosage adjustment is required in patients with mild to severe renal impairment (CrCL <30 mL/min 
and not on dialysis [see section 5.2]). Cabotegravir has not been studied in patients with end-stage 
renal disease on renal replacement therapy. As cabotegravir is greater than 99% protein bound, dialysis 
is not expected to alter exposures of cabotegravir. If administered in a patient on renal replacement 
therapy, cabotegravir should be used with caution. 
 
Hepatic impairment 
No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh 
score A or B). Cabotegravir has not been studied in patients with severe hepatic impairment (Child-
Pugh score C [see section 5.2]). 
If administered in a patient with severe hepatic impairment, cabotegravir should be used with caution. 
 



26 

Paediatric population 
The safety and efficacy of Vocabria in children and adolescents aged under 18 years have not been 
established. No data is available.  
 
Method of administration 
 
Oral use. 
 
Vocabria tablets may be taken with or without food. When taken at the same time as rilpivirine tablets, 
Vocabria tablets should be taken with a meal. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Concomitant use with rifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin or 
phenobarbital (see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
Baseline factors associated with virological failure 
 
Before starting the regimen, it should be taken into account that multivariable analyses indicate that a 
combination of at least 2 of the following baseline factors may be associated with an increased risk of 
virological failure: archived rilpivirine resistance mutations, HIV-1 subtype A6/A1, or 
BMI ≥30 kg/m2. In patients with an incomplete or uncertain treatment history without pre-treatment 
resistance analyses, caution is warranted in the presence of either BMI ≥30 kg/m2 or HIV-1 A6/A1 
subtype (see section 5.1). 
 
Hypersensitivity reactions 
 
Hypersensitivity reactions have been reported in association with other integrase inhibitors. These 
reactions were characterised by rash, constitutional findings and sometimes organ dysfunction, 
including liver injury. While no such reactions have been observed to date in association with 
Vocabria, physicians should remain vigilant and should discontinue Vocabria and other suspected 
medicinal products immediately, should signs or symptoms of hypersensitivity develop (including, but 
not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint 
aches, blisters, oral lesions, conjunctivitis, facial oedema, hepatitis, eosinophilia or angioedema). 
Clinical status, including liver aminotransferases should be monitored and appropriate therapy 
initiated. Administration of oral lead-in is recommended to help identify patients who may be at risk of 
a hypersensitivity reaction (see section 4.2). 
 
Hepatoxicity 
 
Hepatotoxicity has been reported in a limited number of patients receiving Vocabria with or without 
known pre-existing hepatic disease (see section 4.8). 
Monitoring of liver chemistries is recommended and treatment with Vocabria should be discontinued 
if hepatotoxicity is suspected. 
 
HBV/HCV co-infection 
 
Patients with hepatitis B co-infection were excluded from studies with Vocabria. It is not 
recommended to initiate Vocabria in patients with hepatitis B co-infection. Physicians should refer to 
current treatment guidelines for the management of HIV infection in patients co-infected with hepatitis 
B virus. 
Limited data is available in patients with hepatitis C co-infection. Monitoring of liver function is 
recommended in patients with hepatitis C co-infection 



27 

 
Interactions with medicinal products  
 
Caution should be given to prescribing Vocabria tablets with medicinal products that may reduce its 
exposure (see section 4.5).  
 
Polyvalent cation containing antacids are recommended to be taken at least 2 hours before and 4 hours 
after taking Vocabria tablets (see section 4.5). 
 
Transmission of HIV 
 
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. 
 
Immune reactivation 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 Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be evaluated, and 
treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune 
hepatitis) have also been reported to occur in the setting of immune reconstitution, however, the 
reported time to onset is more variable and these events can occur many months after initiation of 
treatment.  
 
Opportunistic infections 
 
Patients should be advised that Vocabria or any other antiretroviral therapy do not cure HIV infection 
and that they may still develop opportunistic infections and other complications of HIV infection. 
Therefore, patients should remain under close clinical observation by physicians experienced in the 
treatment of these associated HIV diseases. 
 
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or 
glucosegalactose malabsorption should not take this medicine. 
 
Excipients 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Vocabria tablets, in combination with rilpivirine tablets, are indicated for the treatment of HIV-1, 
therefore, the prescribing information for rilpivirine tablets should be consulted for associated 
interactions. 
 
Effect of other agents on the pharmacokinetics of cabotegravir 
 
Cabotegravir is primarily metabolised by uridine diphosphate glucuronosyl transferase (UGT) 1A1 and 
to a lesser extent by UGT1A9. Medicinal products which are strong inducers of UGT1A1 or UGT1A9 
are expected to decrease cabotegravir plasma concentrations leading to lack of efficacy (see section 4.3 
and table 5 below). In poor metabolizers of UGT1A1, representing a maximum clinical UGT1A1 
inhibition, the mean AUC, Cmax and Ctau of oral cabotegravir increased by up to 1.5-fold. The impact 
of an UGT1A1 inhibitor may be slightly more pronounced, however, considering the safety margins of 



28 

cabotegravir, this increase is not expected to be clinically relevant. No dosing adjustments for 
Vocabria are, therefore, recommended in the presence of UGT1A1 inhibitors (e.g. atazanavir, 
erlotinib, sorafenib). 
 
Cabotegravir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), 
however, because of its high permeability, no alteration in absorption is expected when co-
administered with either P-gp or BCRP inhibitors. 
 
Effect of cabotegravir on the pharmacokinetics of other medicinal products 
 
In vivo, cabotegravir did not have an effect on midazolam, a cytochrome P450 (CYP) 3A4 probe. In 
vitro, cabotegravir did not induce CYP1A2, CYP2B6, or CYP3A4. 
 
In vitro, cabotegravir inhibited the organic anion transporters (OAT) 1 (IC50=0.81 µM) and OAT3 
(IC50=0.41 µM). Therefore, caution is advised when co-dosing with narrow therapeutic index OAT1/3 
substrate drugs (e.g. methotrexate). 
 
Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter 
concentrations of other anti-retroviral medications including protease inhibitors, nucleoside reverse 
transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry 
inhibitors and ibalizumab. 
 
The drug interaction data provided in Table 2 is obtained from studies with oral cabotegravir (increase 
is indicated as “↑”, decrease as “↓”, no change as “↔”, area under the concentration versus time curve 
as “AUC”, maximum observed concentration as “Cmax”, concentration at end of dosing interval as 
“Cτ”). 
 
Table 2: Drug Interactions 
 

Medicinal products 
by therapeutic areas 

Interaction  
Geometric mean change 
(%)  

Recommendations concerning 
co-administration 

HIV-1 Antiviral medicinal products 
Non-nucleoside 
Reverse Transcriptase 
Inhibitor: 
Etravirine 

Cabotegravir ↔ 
AUC ↑ 1% 
Cmax ↑ 4% 
Cτ ↔ 0% 

Etravirine did not significantly change 
cabotegravir plasma concentration. No dose 
adjustment of Vocabria tablets is necessary. 

Non-nucleoside 
Reverse Transcriptase 
Inhibitor: 
Rilpivirine 

Cabotegravir ↔ 
AUC ↑ 12% 
Cmax ↑ 5% 
Cτ ↑ 14% 
 
Rilpivirine ↔ 
AUC ↓ 1% 
Cmax ↓ 4% 
Cτ ↓ 8% 

Rilpivirine did not significantly change 
cabotegravir plasma concentration. No dose 
adjustment of Vocabria tablets is necessary when 
co-administered with rilpivirine. 

Anticonvulsants 
Carbamazepine 
Oxcarbazepine 
Phenytoin 
Phenobarbital 

Cabotegravir ↓ Metabolic inducers may significantly decrease 
cabotegravir plasma concentrations, concomitant 
use is contraindicated (see section 4.3). 



29 

Antacids 
Antacids (e.g. 
magnesium, 
aluminium, or 
calcium) 
 

Cabotegravir ↓ Co-administration of antacid supplements has the 
potential to decrease oral cabotegravir absorption 
and has not been studied. 
Antacid products containing polyvalent cations are 
recommended to be administered at least 2 hours 
before or 4 hours after oral Vocabria (see section 
4.4). 

Antimycobacterials 
Rifampicin Cabotegravir ↓ 

AUC ↓ 59% 
Cmax ↓ 6% 

Rifampicin significantly decreased cabotegravir 
plasma concentration which is likely to result in 
loss of therapeutic effect. Dosing recommendations 
for co-administration of Vocabria with rifampicin 
have not been established and co-administration of 
Vocabria with rifampicin is contraindicated (see 
section 4.3).  

Rifapentine Cabotegravir ↓ Rifapentine may significantly decrease 
cabotegravir plasma concentrations, concomitant 
use is contraindicated (see section 4.3). 

Rifabutin 
 

Cabotegravir ↓ 
AUC ↓ 21% 
Cmax ↓ 17% 
Cτ ↓ 8% 

Rifabutin did not significantly change cabotegravir 
plasma concentration. No dose adjustment is 
required. 
Prior to initiation of oral cabotegravir therapy, the 
prescribing information for Vocabria injection 
should be consulted regarding concomitant use 
with rifabutin. 

Oral Contraceptives 
Ethinyl estradiol (EE) 
and Levonorgestrel 
(LNG) 

EE ↔ 
AUC ↑ 2% 
Cmax ↓ 8% 
Cτ ↔ 0% 
 
LNG ↔ 
AUC ↑ 12% 
Cmax ↑ 5% 
Cτ ↑ 7% 

Cabotegravir did not significantly change ethinyl 
estradiol and levonorgestrel plasma concentrations 
to a clinically relevant extent. No dose adjustment 
of oral contraceptives is necessary when co-
administered with Vocabria tablets. 

 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are a limited amount of data from the use of cabotegravir in pregnant women. The effect of 
Vocabria on human pregnancy is unknown. 
 
Cabotegravir was not teratogenic when studied in pregnant rats and rabbits but, exposures higher than 
the therapeutic dose showed reproductive toxicity in animals (see section 5.3). The relevance to human 
pregnancy is unknown. 
 
Vocabria tablets are not recommended during pregnancy unless the expected benefit justifies the 
potential risk to the foetus. 
 
Breast-feeding 
 
It is expected that cabotegravir will be secreted into human milk based on animal data, although this 
has not been confirmed in humans.  
 



30 

It is recommended that HIV infected women do not breast-feed their infants under any circumstances 
in order to avoid transmission of HIV. 
 
Fertility 
 
There are no data on the effects of cabotegravir on human male or female fertility. Animal studies 
indicate no effects of cabotegravir on male or female fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Patients should be informed that dizziness, fatigue and somnolence has been reported during treatment 
with Vocabria. The clinical status of the patient and the adverse reaction profile of Vocabria should be 
borne in mind when considering the patient’s ability to drive or operate machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reaction (ARs) from monthly dosing studies were headache (up 
to 12%) and pyrexia4 (10%). 
The most frequently reported ARs, considered by the investigator as causally related, from ATLAS-
2M every 2 month dosing were headache (7%) and pyrexia4 (7%). 
 
Tabulated list of adverse reactions 
 
The ARs identified for cabotegravir and rilpivirine are listed in Table 3 by body system organ class 
and frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), 
uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). 
 
Table 3: Tabulated summary of adverse reactions1 

 
MedDRA System Organ 
Class (SOC) 

Frequency 
Category 

ARs for Vocabria + rilpivirine regimen 

Psychiatric disorders Common Depression 
Anxiety 
Abnormal dreams 
Insomnia 

Nervous system disorders Very common Headache 

Common  Dizziness 

Uncommon Somnolence 

Gastrointestinal disorders Common Nausea 
Vomiting 
Abdominal pain2 

Flatulence 
Diarrhoea 

Hepatobiliary Disorders Uncommon Hepatotoxicity 

Skin and subcutaneous tissue 
disorders 

Common Rash3 



31 

Musculoskeletal and 
connective tissue disorders 

Common Myalgia 

General disorders and 
administrative site conditions 

Very common Pyrexia4 

Common Fatigue 
Asthenia 
Malaise 

Investigations Common Weight increased 

Uncommon Transaminase increased 
Blood bilirubin increased 

1 The frequency of the identified ARs are based on all reported occurrences of the events and are not limited to 
those considered at least possibly related by the investigator. 
2 Abdominal pain includes the following grouped MedDRA preferred term: upper abdominal pain. 
3 Rash includes the following grouped MedDRA preferred terms: rash, rash erythematous, rash generalised, rash 
macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic. 
4 Pyrexia includes the following grouped MedDRA preferred terms: feeling hot, body temperature increased. 
 
Description of selected adverse reactions 
 
Weight increased 
At the Week 48 time point, subjects in studies FLAIR and ATLAS, who received Vocabria plus 
rilpivirine gained a median of 1.5 kg in weight; subjects continuing on their current antiretroviral 
therapy (CAR) gained a median of 1.0 kg (pooled analysis). In the individual studies FLAIR and 
ATLAS, the median weight gains in the Vocabria plus rilpivirine arms were 1.3 kg and 1.8 kg 
respectively, compared to 1.5 kg and 0.3 kg in the CAR arms. 
 
At the 48 week timepoint, in ATLAS-2M the median weight gain in both the monthly and 2-monthly 
Vocabria plus rilpivirine dosing arms was 1.0 kg. 
 
Changes in laboratory chemistries 
Small, non-progressive increases in total bilirubin (without clinical jaundice) were observed with 
treatment with Vocabria plus rilpivirine. These changes are not considered clinically relevant as they 
likely reflect competition between cabotegravir and unconjugated bilirubin for a common clearance 
pathway (UGT1A1). 
 
Elevated transaminases (ALT/AST) were observed in subjects receiving Vocabria plus rilpivirine 
during clinical studies. These elevations were primarily attributed to acute viral hepatitis. A few 
subjects on oral therapy had transaminase elevations attributed to suspected drug-related 
hepatotoxicity; these changes were reversible upon discontinuation of treatment (see section 4.4). 
 
Elevated lipases were observed during clinical trials with Vocabria plus rilpivirine; Grade 3 and 4 
lipase increases occurred at a higher incidence with Vocabria plus rilpivirine compared with CAR. 
These elevations were generally asymptomatic and did not lead to Vocabria plus rilpivirine 
discontinuation. One case of fatal pancreatitis with Grade 4 lipase and confounding factors (including 
history of pancreatitis) has been reported in study ATLAS-2M, for which causality to the injection 
regimen could not be ruled out. 
 
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. 

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


32 

 
4.9 Overdose 
 
There is no specific treatment for Vocabria overdose. If overdose occurs, the patient should be treated 
supportively with appropriate monitoring as necessary. 
 
Cabotegravir is known to be highly protein bound in plasma; therefore, dialysis is unlikely to be 
helpful in removal of medicinal product from the body. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiviral for systemic use, integrase inhibitor, ATC code: J05AJ04 
 
Mechanism of action 
 
Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand 
transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV 
replication cycle. 
 
Pharmacodynamic effects 
 
Antiviral activity in cell culture 
Cabotegravir exhibited antiviral activity against laboratory strains of wild-type HIV-1 with mean 
concentration of cabotegravir necessary to reduce viral replication by 50 percent (EC50) values of 
0.22 nM in peripheral blood mononuclear cells (PBMCs), 0.74 nM in 293T cells and 0.57 nM in MT-4 
cells. Cabotegravir demonstrated antiviral activity in cell culture against a panel of 24 HIV-1 clinical 
isolates (three in each group of M clades A, B, C, D, E, F, and G, and 3 in group O) with EC50 values 
ranging from 0.02 nM to 1.06 nM for HIV-1. Cabotegravir EC50 values against three HIV-2 clinical 
isolates ranged from 0.10 nM to 0.14 nM. No clinical data is available in patients with HIV-2. 
 
Antiviral Activity in combination with other antiviral medicines 
No medicines with inherent anti-HIV activity were antagonistic to cabotegravir’s antiretroviral activity 
(in vitro assessments were conducted in combination with rilpivirine, lamivudine, tenofovir and 
emtricitabine). 
 
Resistance in vitro 
Isolation from wild-type HIV-1 and activity against resistant strains: Viruses with >10-fold increase in 
cabotegravir EC50 were not observed during the 112-day passage of strain IIIB. The following 
integrase (IN) mutations emerged after passaging wild type HIV-1 (with T124A polymorphism) in the 
presence of cabotegravir: Q146L (fold-change [FC] range 1.3-4.6), S153Y (FC range 3.6-8.4), and 
I162M (FC = 2.8). As noted above, the detection of T124A is selection of a pre-existing minority 
variant that does not have differential susceptibility to cabotegravir. No amino acid substitutions in the 
integrase region were selected when passaging the wild-type HIV-1 NL-432 in the presence of 6.4 nM 
of cabotegravir through Day 56. 
 
Among the multiple mutants, the highest FC was observed with mutants containing Q148K or Q148R. 
E138K/Q148H resulted in a 0.92-fold decrease in susceptibility to cabotegravir but E138K/Q148R 
resulted in a 12-fold decrease in susceptibility and E138K/Q148K resulted in an 81-fold decrease in 
susceptibility to cabotegravir. G140C/Q148R and G140S/Q148R resulted in a 22- and 12-fold 
decrease in susceptibility to cabotegravir, respectively. While N155H did not alter susceptibility to 
cabotegravir, N155H/Q148R resulted in a 61-fold decrease in susceptibility to cabotegravir. Other 
multiple mutants, which resulted in a FC between 5 and 10, are: T66K/L74M (FC=6.3), 
G140S/Q148K (FC=5.6), G140S/Q148H (FC=6.1) and E92Q/N155H (FC=5.3). 
 



33 

Resistance in vivo 
The number of subjects who met Confirmed Virologic Failure (CVF) criteria was low across the 
pooled FLAIR and ATLAS trials. In the pooled analysis, there were 7 CVFs on cabotegravir plus 
rilpivirine (7/591, 1.2%) and 7 CVFs on current antiretroviral regimen (7/591, 1.2%). The three CVFs 
on cabotegravir plus rilpivirine in FLAIR with resistance data had Subtype A1. In addition, 2 of the 3 
CVFs had treatment-emergent integrase inhibitor resistance associated substitution Q148R while one 
of the three had G140R with reduced phenotypic susceptibility to cabotegravir. All 3 CVFs carried one 
rilpivirine resistance-associated substitution: K101E, E138E/A/K/T or E138K, and two of the three 
showed reduced phenotypic susceptibility to rilpivirine. The 3 CVFs in ATLAS had subtype A, A1 
and AG. One of the three CVFs carried the INI resistance-associated substitution N155H at failure 
with reduced cabotegravir phenotype susceptibility. All three CVFs carried one rilpivirine resistance-
associated substitution at failure: E138A, E138E/K or E138K, and showed reduced phenotypic 
susceptibility to rilpivirine. In two of these three CVFs, the rilpivirine resistance-associated 
substitutions observed at failure were also observed at baseline in PBMC HIV-1 DNA. The seventh 
CVF (FLAIR) never received an injection. 
 
The substitutions associated with resistance to long-acting cabotegravir injection, observed in the 
pooled ATLAS and FLAIR trials were G140R (n=1), Q148R (n=2), and N155H (n=1). 
 
In the ATLAS-2M study 10 subjects met CVF criteria through Week 48: 8 subjects (1.5%) in the Q8W 
arm and 2 subjects (0.4%) in the Q4W arm. Eight subjects met CVF criteria at or before the Week 24 
timepoint. 
 
At Baseline in the Q8W arm, 5 subjects had rilpivirine resistance-associated mutations of Y181Y/C + 
H221H/Y, Y188Y/F/H/L, Y188L, E138A or E138E/A and 1 subject contained cabotegravir resistance 
mutation, G140G/R (in addition to the above Y188Y/F/H/L rilpivirine resistance-associated mutation). 
At the suspected virologic failure (SVF) timepoint in the Q8W arm, 6 subjects had rilpivirine 
resistance-associated mutations with 2 subjects having an addition of K101E and 1 subject having an 
addition of E138E/K from Baseline to SVF timepoint. Rilpivirine FC was above the clinical cut-off for 
7 subjects and ranged from 2.4 to 15. Five of the 6 subjects with rilpivirine resistance-associated 
substitution, also had INSTI resistance-associated substitutions, N155H (n=2); Q148R; 
Q148Q/R+N155N/H (n=2). INSTI substitution, L74I, was seen in 4/7 subjects. The Integrase genotype 
and phenotype assay failed for one subject and cabotegravir phenotype was unavailable for another. 
FCs for the Q8W subjects ranged from 0.6 to 9.1 for cabotegravir, 0.8 to 2.2 for dolutegravir and 0.8 to 
1.7 for bictegravir. 
 
In the Q4W arm, neither subject had any rilpivirine or INSTI resistance-associated substitutions at 
Baseline. One subject had the NNRTI substitution, G190Q, in combination with the NNRTI 
polymorphism, V189I. At SVF timepoint, one subject had on-treatment rilpivirine resistance-
associated mutations, K101E + M230L and the other retained the G190Q + V189I NNRTI 
substitutions with the addition of V179V/I. Both subjects showed reduced phenotypic susceptibility to 
rilpivirine. Both subjects also had INSTI resistance-associated mutations, either Q148R + E138E/K or 
N155N/H at SVF and 1 subject had reduced susceptibility to cabotegravir. Neither subject had the 
INSTI substitution, L74I. FCs for the Q4W subjects were 1.8 and 4.6 for cabotegravir, 1.0 and 1.4 for 
dolutegravir and 1.1 and 1.5 for bictegravir. 
 
Clinical efficacy and safety 
 
The efficacy of Vocabria plus rilpivirine has been evaluated in two Phase III randomised, multicentre, 
active-controlled, parallel-arm, open-label, non-inferiority studies, FLAIR (study 201584) and ATLAS 
(study 201585). The primary analysis was conducted after all subjects completed their Week 48 visit 
or discontinued the study prematurely. 
 
Patients virologically suppressed (on prior dolutegravir based regimen for 20 weeks) 
In FLAIR, 629 HIV-1-infected, antiretroviral treatment (ART)-naive subjects received a dolutegravir 
integrase strand transfer inhibitor (INSTI) containing regimen for 20 weeks (either 
dolutegravir/abacavir/lamivudine or dolutegravir plus 2 other nucleoside reverse transcriptase 



34 

inhibitors if subjects were HLA-B*5701 positive). Subjects who were virologically suppressed (HIV-1 
RNA <50 copies per mL, n=566) were then randomised (1:1) to receive either the Vocabria plus 
rilpivirine regimen or remain on the current antiretroviral (CAR) regimen. Subjects randomised to 
receive the Vocabria plus rilpivirine regimen, initiated treatment with oral lead-in dosing with one 30 
mg Vocabria tablet plus one 25 mg rilpivirine tablet, daily, for at least 4 weeks, followed by treatment 
with Vocabria injection (month 1: 600 mg injection, month 2 onwards: 400 mg injection) plus 
rilpivirine injection (month 1: 900 mg injection, month 2 onwards: 600 mg injection) every month for 
an additional 44 weeks. This study was extended to 96 weeks. 
 
Patients virologically suppressed (stable on prior ARV therapy for at least 6 months) 
In ATLAS, 616 HIV-1-infected, ART-experienced, virologically-suppressed (for at least 6 months) 
subjects (HIV-1 RNA <50 copies per mL) were randomised (1:1) and received either the Vocabria 
plus rilpivirine regimen or remained on the CAR regimen. Subjects randomised to receive the 
Vocabria plus rilpivirine regimen, initiated treatment with oral lead-in dosing with one 30 mg 
Vocabria tablet plus one 25 mg rilpivirine tablet, daily for at least 4 weeks, followed by treatment with 
Vocabria injection (month 1: 600 mg injection, month 2 onwards: 400 mg injection) plus rilpivirine 
injection (month 1: 900 mg injection, month 2 onwards: 600 mg injection) every month for an 
additional 44 weeks. In ATLAS, 50%, 17%, and 33% of subjects received an NNRTI, PI, or INI 
(respectively) as their baseline third treatment medicine class prior to randomisation and this was 
similar between treatment arms.  
 
Pooled data 
At baseline, in the pooled analysis, for the Vocabria plus rilpivirine arm, the median age of subjects 
was 38 years, 27% were female, 27% were non-white, 1% were ≥ 65 years and 7% had CD4+ cell 
count less than 350 cells per mm3; these characteristics were similar between treatment arms. 
 
The primary endpoint of both studies was the proportion of subjects with plasma HIV-1 RNA ≥50 
copies/mL at week 48 (snapshot algorithm for the ITT-E population). 
 
In a pooled analysis of the two pivotal studies, Vocabria plus rilpivirine was non-inferior to CAR on 
the proportion of subjects having plasma HIV-1 RNA ≥50 c/mL (1.9% and 1.7% respectively) at 
Week 48. The adjusted treatment difference between Vocabria plus rilpivirine and CAR (0.2; 95% CI: 
-1.4, 1.7) for the pooled analysis met the non-inferiority criterion (upper bound of the 95% CI below 
4%).  
 
The primary endpoint and other week 48 outcomes, including outcomes by key baseline factors, for 
FLAIR and ATLAS are shown in Tables 4 and 5. 
 



35 

Table 4   Virologic Outcomes of randomised treatment of FLAIR and ATLAS at 48 
Weeks (Snapshot analysis) 

 
 FLAIR ATLAS Pooled Data 
 Vocabria 

+ RPV 
N=283 

CAR 
N=283 

Vocabria 
+ RPV 
N=308 

CAR 
N=308 

Vocabria 
+RPV 
N=591 

CAR 
N=591 

HIV-1 RNA≥50 
copies/mL† (%) 6 (2.1) 7 (2.5) 5 (1.6) 3 (1.0) 11 (1.9) 10 (1.7) 

Treatment 
Difference % 
(95% CI)*  

-0.4 (-2.8,2.1) 0.7 (-1.2, 2.5) 0.2 (-1.4, 1.7) 

HIV-1 RNA <50 
copies/mL (%) 

265 (93.6) 264 (93.3) 285 (92.5) 294 (95.5) 550 (93.1) 558 (94.4) 

Treatment 
Difference % (95% 
CI)* 

0.4 (-3.7, 4.5) 
 

-3.0 (-6.7, 0.7) -1.4 (-4.1, 1.4) 

No virologic data 
at Week 48 
window (%) 

12 (4.2) 12 (4.2) 18 (5.8) 11 (3.6) 30 (5.1) 23 (3.9) 

Reasons 
Discontinued 
study/study drug 
due to adverse 
event or death (%) 

8 (2.8) 2 (0.7) 11 (3.6) 5 (1.6) 19 (3.2) 7 (1.2) 

Discontinued 
study/study drug 
for other reasons 
(%) 

4 (1.4) 10 (3.5) 7 (2.3) 6 (1.9) 11 (1.9) 16 (2.7) 

Missing data during 
window but on 
study (%) 

0 0 0 0 0 0 

* Adjusted for baseline stratification factors. 
† Includes subjects who discontinued for lack of efficacy, discontinued while not supressed. 
N = Number of subjects in each treatment group, CI = confidence interval, CAR = current antiviral regimen. 
 
Table 5  Proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL at Week 48 for 

key baseline factors (Snapshot Outcomes). 
 

Baseline factors 

Pooled Data from FLAIR and ATLAS 
Vocabria+RPV 

N=591 
n/N (%) 

CAR 
N=591 

n/N (%) 
Baseline CD4+ 
(cells/ mm3) 

<350  0/42 2/54 (3.7) 
≥350 to <500 5/120 (4.2) 0/117 
≥500 6/429 (1.4) 8 / 420 (1.9) 

Gender Male 6/429 (1.4) 9/423 (2.1) 
 Female 5/162 (3.1) 1/168 (0.6) 
Race White 9/430 (2.1) 7/408 (1.7) 

Black African/American 2/109 (1.8) 3/133 (2.3) 
  Asian/Other 0/52 0/48 
BMI <30 kg/m2 6/491 (1.2) 8/488 (1.6) 

≥30 kg/m2 5/100 (5.0) 2/103 (1.9) 
Age (years) <50 9/492 (1.8) 8/466 (1.7) 

≥50 2/99 (2.0) 2/125 (1.6) 



36 

Baseline 
antiviral therapy 
at randomisation 

PI 1/51 (2.0) 0/54 
INI 6/385 (1.6) 9/382 (2.4) 
NNRTIs 4/155 (2.6) 1/155 (0.6) 

BMI= body mass index 
PI= Protease inhibitor 
INI= Integrase inhibitor 
NNRTI= non-nucleoside reverse transcriptase inhibitor 
 
In both the FLAIR and ATLAS studies, treatment differences across baseline characteristics (CD4+ 
count, gender, race, BMI, age, baseline third agent treatment class) were comparable. 
 
In the FLAIR study at 96 Weeks, the results remained consistent with the results at 48 Weeks. The 
proportion of subjects having plasma HIV-1 RNA ≥50 c/mL in Vocabria plus rilpivirine (n=283) and 
CAR (n=283) was 3.2% and 3.2% respectively (adjusted treatment difference between Vocabria plus 
rilpivirine and CAR [0.0; 95% CI: -2.9, 2.9]). The proportion of subjects having plasma HIV-1 RNA 
<50 c/mL in Vocabria plus rilpivirine and CAR was 87% and 89%, respectively (adjusted treatment 
difference between Vocabria plus rilpivirine and CAR [-2.8; 95% CI: -8.2, 2.5]). 
 
Every 2 month dosing 
Patients virologically suppressed (stable on prior ARV therapy for at least 6 months) 
The efficacy and safety of Vocabria injection given every 2 months, has been evaluated in one Phase 
IIIb randomised, multicentre, parallel-arm, open-label, non-inferiority study, ATLAS-2M (207966). 
The primary analysis was conducted after all subjects completed their Week 48 visit or discontinued 
the study prematurely. 
In ATLAS-2M, 1045 HIV-1 infected, ART experienced, virologically suppressed subjects were 
randomised (1:1) and received a Vocabria plus rilpivirine injection regimen administered either every 
2 months or monthly. Subjects initially on non-cabotegravir/rilpivirine treatment received oral lead-in 
treatment comprising one 30 mg Vocabria tablet plus one 25 mg rilpivirine tablet, daily, for at least 4 
weeks. Subjects randomised to monthly Vocabria injections (month 1: 600 mg injection, month 2 
onwards: 400 mg injection) and rilpivirine injections (month 1: 900 mg injection, month 2 onwards: 
600 mg injection) received treatment for an additional 44 weeks. Subjects randomised to every 2 
month Vocabria injections (600 mg injection at months 1, 2, 4 and every 2 months thereafter) and 
rilpivirine injections (900 mg injection at months 1, 2, 4 and every 2 months thereafter) received 
treatment for an additional 44 weeks. Prior to randomisation, 63%, 13% and 24% of subjects received 
Vocabria plus rilpivirine for 0 weeks, 1 to 24 weeks and >24 weeks, respectively. 
 
At baseline, the median age of subjects was 42 years, 27% were female, 27% were non-white, 4% 
were ≥ 65 years and 6% had a CD4+ cell count less than 350 cells per mm3; these characteristics were 
similar between the treatment arms. 
The primary endpoint in ATLAS-2M was the proportion of subjects with a plasma HIV-1 RNA 
≥50 c/mL at Week 48 (snapshot algorithm for the ITT-E population).  
 
In ATLAS-2M, Vocabria and rilpivirine administered every 2 months was non-inferior to Vocabria 
and rilpivirine administered every month on the proportion of subjects having plasma HIV-1 RNA ≥50 
c/mL (1.7% and 1.0% respectively) at Week 48. The adjusted treatment difference between Vocabria 
and rilpivirine administered every 2 months and every month (0.8; 95% CI: -0.6, 2.2) met the non-
inferiority criterion (upper bound of the 95% CI below 4%). 
 



37 

Table 6  Virologic Outcomes of Randomised Treatment of ATLAS-2M at 48 Weeks 
(Snapshot analysis) 
 

 2 month Dosing (Q8W) Monthly Dosing (Q4W) 
 N=522 (%) N=523 (%) 
HIV-1 RNA≥50 copies/mL† (%) 9 (1.7) 5 (1.0) 
Treatment Difference % (95% 
CI)*  

0.8 (-0.6, 2.2) 
 

HIV-1 RNA <50 copies/mL (%) 492 (94.3) 489 (93.5) 
Treatment Difference % (95% CI)* 0.8 (-2.1, 3.7) 
No virologic data at week 48 
window 

21 (4.0) 29 (5.5) 

Reasons:  
Discontinued study due to AE or 
death (%) 

9 (1.7) 13 (2.5) 

Discontinued study for other 
reasons (%) 

12 (2.3) 16 (3.1) 

On study but missing data in 
window (%) 

0 0 

* Adjusted for baseline stratification factors. 
† Includes subjects who discontinued for lack of efficacy, discontinued while not suppressed. 
N = Number of subjects in each treatment group, CI = confidence interval, CAR = current antiviral regimen. 
 
Table 7 Proportion of Subjects with Plasma HIV-1 RNA ≥50 copies/mL at Week 48 for 

key baseline factors (Snapshot Outcomes). 
 

Baseline factors Number of HIV-1 RNA ≥50 c/mL/Total Assessed 
(%) 
2 Month Dosing 
(Q8W) 

Monthly dosing (Q4W) 

Baseline CD4+ cell 
count (cells/mm3) 

<350 1/ 35 (2.9) 1/ 27 (3.7) 

350 to <500 1/ 96 (1.0) 0/ 89 

≥500 7/391 (1.8) 4/407 (1.0) 

Gender Male 4/385 (1.0) 5/380 (1.3) 

Female 5/137 (3.5) 0/143 

Race White 5/370 (1.4) 5/393 (1.3) 

Non-White 4/152 (2.6) 0/130 

Black/African 
American 

4/101 (4.0) 0/ 90 

Non-
Black/African 
American 

5/421 (1.2) 5/421 (1.2) 

BMI <30 kg/m2 3/409 (0.7) 3/425 (0.7) 

≥30 kg/m2 6/113 (5.3) 2/98 (2.0) 

Age (years) <35 4/137 (2.9) 1/145 (0.7) 



38 

BMI= body mass index 
 
In the ATLAS-2M study, treatment differences on the primary endpoint across baseline 
characteristics (CD4+ lymphocyte count, gender, race, BMI, age and prior exposure to 
cabotegravir/rilpivirine) were not clinically meaningful. 
 
Post-hoc analysis  
Multivariable analyses of pooled phase 3 studies (ATLAS, FLAIR and ATLAS-2M), including data 
from 1039 HIV-infected adults with no prior exposure to Vocabria plus rilpivirine, examined the 
influence of baseline viral and participant characteristics, dosing regimen, and post-baseline plasma 
drug concentrations on confirmed virologic failure (CVF) using regression modelling with a variable 
selection procedure. Through Week 48 in these studies, 13/1039 (1.25%) participants had CVF while 
receiving cabotegravir and rilpivirine. 
  
Four covariates were significantly associated (P<0.05 for each adjusted odds ratio) with increased risk 
of CVF: rilpivirine resistance mutations at baseline identified by proviral DNA genotypic assay, HIV-
1 subtype A6/A1 (associated with integrase L74I polymorphism), rilpivirine trough concentration 4 
weeks following initial injection dose, body mass index of at least 30 kg/m2 (associated with 
cabotegravir pharmacokinetics). Other variables including Q4W or Q8W dosing, female gender, or 
other viral subtypes (non A6/A1) had no significant association with CVF. No baseline factor, when 
present in isolation, was predictive of virologic failure. However, a combination of at least 2 of the 
following baseline factors was associated with an increased risk of CVF: rilpivirine resistance 
mutations, HIV-1 subtype A6/A1, or BMI ≥30 kg/m2 (see Table 8). 
 
Table 8  Week 48 outcomes by presence of key baseline factors of rilpivirine resistance 

associated mutations, Subtype A6/A11 and BMI ≥30 kg/m2 

 

Baseline Factors (number) Virologic Successes (%)2 Confirmed Virologic Failure 
(%)3 

0 694/732 (94.8) 3/732 (0.41) 
1 261/272 (96.0) 1/272 (0.37)4 

≥2 25/35 (71.4) 9/35 (25.7)5 

TOTAL 
(95% Confidence Interval) 

980/1039 (94.3) 
(92.74%, 95.65%) 

13/1039 (1.25) 
(0.67%, 2.13%) 

1 HIV-1 subtype A1 or A6 classification based on Los Alamos National Library panel from HIV Sequence 
database (June 2020) 
2 Based on the FDA Snapshot algorithm of RNA <50 copies/mL.  
3 Defined as two consecutive measurements of HIV RNA >200 copies/mL. 
4 Positive Predictive Value (PPV) <1%; Negative Predictive Value (NPV) 98%; sensitivity 8%; specificity 74% 
5 PPV 26%; NPV 99.6%; sensitivity 69%; specificity 97.5% 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Vocabria tablets in one or more subsets of the paediatric population in the treatment of HIV-1 
infection. 
 
5.2 Pharmacokinetic properties 

35 to <50 3/242 (1.2) 2/239 (0.8) 

≥50 2/143 (1.4) 2/139 (1.4) 

Prior exposure 
CAB/RPV 

None 5/327 (1.5) 5/327 (1.5) 

1-24 weeks 3/69 (4.3) 0/68 

>24 weeks 1/126 (0.8) 0/128 



39 

 
Cabotegravir pharmacokinetics is similar between healthy and HIV-infected subjects. The PK 
variability of cabotegravir is moderate. In Phase I studies in healthy subjects, between-subject CVb% 
for AUC, Cmax, and Ctau ranged from 26 to 34% across healthy subject studies and 28 to 56% across 
HIV-1 infected subject studies. Within-subject variability (CVw%) is lower than between-subject 
variability. 
Table 9  Pharmacokinetic parameters following cabotegravir orally once daily  
 

Dosing Phase 
Dosage 

Regimen 

Geometric Mean (5th, 95th Percentile)a 
AUC(0-tau)

b 
(µ•h/mL) 

Cmax 
(µ/mL) 

Ctau 
(µ/mL) 

Oral lead-inc 30 mg  
once daily 

145 
(93.5, 224) 

8.0 
(5.3, 11.9) 

4.6 
(2.8, 7.5) 

a Pharmacokinetic parameter values based on pooled FLAIR and ATLAS individual post-hoc estimates from 
cabotegravir population pharmacokinetic model (n = 581) 

b tau is dosing interval: 24 hours for oral administration; 1 month for IM injections of extended-release injectable 
suspension. 

c Oral lead-in pharmacokinetic parameter values represent steady-state. 
 
Absorption 
 
Cabotegravir is rapidly absorbed following oral administration, with median Tmax at 3 hours post dose 
for tablet formulation. With once daily dosing, pharmacokinetic steady-state is achieved by 7 days. 
Cabotegravir may be administered with or without food. Food increased the extent of absorption of 
cabotegravir. Bioavailability of cabotegravir is independent of meal content: high fat meals increased 
cabotegravir AUC(0-∞) by 14% and increased Cmax by 14% relative to fasted conditions. These 
increases are not clinically significant. 
The absolute bioavailability of cabotegravir has not been established. 
 
Distribution 
 
Cabotegravir is highly bound (>99%) to human plasma proteins, based on in vitro data. Following 
administration of oral tablets, the mean apparent oral volume of distribution (Vz/F) in plasma was 
12.3 L. In humans, the estimate of plasma cabotegravir Vc/F was 5.27 L and Vp/F was 2.43 L. These 
volume estimates, along with the assumption of high bioavailability, suggest some distribution of 
cabotegravir to the extracellular space. 
 
Cabotegravir is present in the female and male genital tract. Median cervical and vaginal tissue:plasma 
ratios ranged from 0.16 to 0.28 and median rectal tissue:plasma ratios were ≤0.08 following a single 
400 mg intramuscular injection (IM) at 4, 8, and 12 weeks after dosing. 
 
Cabotegravir is present in cerebrospinal fluid (CSF). In HIV-infected subjects receiving a regimen of 
cabotegravir injection plus rilpivirine injection, the cabotegravir CSF to plasma concentration ratio 
[median (range)] (n=16) was 0.003(range: 0.002 to 0.004) one week following a steady-state long 
acting cabotegravir (Q4W or Q8W) injection. Consistent with therapeutic cabotegravir concentrations 
in the CSF, CSF HIV-1 RNA (n=16) was <50 c/mL in 100% and <2 c/mL in 15/16 (94%) of subjects. 
At the same time point, plasma HIV-1 RNA (n=18) was <50 c/mL in 100% and <2 c/mL in 12/18 
(66.7%) of subjects. 
 
In vitro, cabotegravir was not a substrate of organic anion transporting polypeptide (OATP) 1B1, 
OATP1B3 or organic cation transporter (OCT1). 
 
Biotransformation 
 
Cabotegravir is primarily metabolised by UGT1A1 with a minor UGT1A9 component. Cabotegravir is 
the predominant circulating compound in plasma, representing > 90% of plasma total radiocarbon. 
Following oral administration in humans, cabotegravir is primarily eliminated through metabolism; 



40 

renal elimination of unchanged cabotegravir is low (<1% of the dose). Forty-seven percent of the total 
oral dose is excreted as unchanged cabotegravir in the faeces. It is unknown if all or part of this is due 
to unabsorbed drug or biliary excretion of the glucuronide conjugate, which can be further degraded to 
form the parent compound in the gut lumen. Cabotegravir was observed to be present in duodenal bile 
samples. The glucuronide metabolite was also present in some but not all of the duodenal bile samples. 
Twenty-seven percent of the total oral dose is excreted in the urine, primarily as a glucuronide 
metabolite (75% of urine radioactivity, 20% of total dose). 
 
Cabotegravir is not a clinically relevant inhibitor of the following enzymes and transporters: CYP1A2, 
CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A1, UGT1A3, 
UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B15, and UGT2B17, P-gp, BCRP, Bile salt 
export pump (BSEP), OCT1, OCT2, OATP1B1, OATP1B3, multidrug and toxin extrusion transporter 
(MATE) 1, MATE 2-K, multidrug resistance protein (MRP) 2 or MRP4. 
 
Elimination 
 
Cabotegravir has a mean terminal half-life of 41 h and an apparent clearance (CL/F) of 0.21 L per 
hour. 
 
Polymorphisms 
In a meta-analysis of healthy and HIV-infected subject trials, subjects with UGT1A1 genotypes 
conferring poor cabotegravir metabolism had a 1.3- to 1.5-fold mean increase in steady-state 
cabotegravir AUC, Cmax, and Ctau compared with subjects with genotypes associated with normal 
metabolism via UGT1A1. These differences are not considered clinically relevant. No dose adjustment 
is required in subjects with UGT1A1 polymorphisms. 
 
Special patient populations 
 
Gender 
Population pharmacokinetic analyses revealed no clinically relevant effect of gender on the exposure 
of cabotegravir, therefore no dose adjustment is required on the basis of gender. 
 
Race 
Population pharmacokinetic analyses revealed no clinically relevant effect of race on the exposure of 
cabotegravir, therefore no dosage adjustment is required on the basis of race. 
 
Body Mass Index (BMI) 
Population pharmacokinetic analyses revealed no clinically relevant effect of BMI on the exposure of 
cabotegravir, therefore no dose adjustment is required on the basis of BMI. 
 
Elderly 
Population pharmacokinetic analysis of cabotegravir revealed no clinically relevant effect of age on 
cabotegravir exposure. Pharmacokinetic data for cabotegravir in subjects of >65 years old are limited. 
 
Renal impairment 
No clinically important pharmacokinetic differences between subjects with severe renal impairment 
(CrCL <30 mL/min and not on dialysis) and matching healthy subjects were observed. No dosage 
adjustment is necessary for patients with mild to severe renal impairment (not on dialysis). 
Cabotegravir has not been studied in patients on dialysis. 
 
Hepatic impairment 
No clinically important pharmacokinetic differences between subjects with moderate hepatic 
impairment and matching healthy subjects were observed. No dosage adjustment is necessary for 
patients with mild to moderate hepatic impairment (Child-Pugh Score A or B). The effect of severe 
hepatic impairment (Child-Pugh Score C) on the pharmacokinetics of cabotegravir has not been 
studied. 
 



41 

5.3 Preclinical safety data 
 
Carcinogenesis and mutagenesis 
 
Cabotegravir was not mutagenic or clastogenic using in vitro tests in bacteria and cultured mammalian 
cells, and an in vivo rodent micronucleus assay. Cabotegravir was not carcinogenic in long term 
studies in the mouse and rat. 
 
Reproductive toxicology studies 
 
No effect on male or female fertility was observed in rats treated with cabotegravir at oral doses up to 
1000 mg/kg/day (>20 times the exposure in humans at the maximum recommended dose). 
 
In an embryo-foetal development study there were no adverse developmental outcomes following oral 
administration of cabotegravir to pregnant rabbits up to a maternal toxic dose of 2,000 mg/kg/day 
(0.66 times the exposure in humans at the MRHD) or to pregnant rats at doses up to 1,000 mg/kg/day 
(>30 times the exposure in humans at the MRHD). In rats, alterations in foetal growth (decreased body 
weights) were observed at 1,000 mg/kg/day. Studies in pregnant rats showed that cabotegravir crosses 
the placenta and can be detected in foetal tissue. 
 
In rat pre- and post-natal (PPN) studies cabotegravir reproducibly induced a delayed onset of 
parturition, and an increase in the number of stillbirths and neonatal mortalities at 1,000 mg/kg/day 
(>30 times the exposure in humans at the MRHD). A lower dose of 5 mg/kg/day (approximately 10 
times the exposure in humans at the MRHD) cabotegravir was not associated with delayed parturition 
or neonatal mortality. In rabbit and rat studies there was no effect on survival when foetuses were 
delivered by caesarean section. Given the exposure ratio, the relevance to humans is unknown. 
 
Repeated dose toxicity 
 
The effect of prolonged daily treatment with high doses of cabotegravir has been evaluated in repeat 
oral dose toxicity studies in rats (26 weeks) and in monkeys (39 weeks). There were no drug-related 
adverse effects in rats or monkeys given cabotegravir orally at doses up to 1,000 mg/kg/day or 
500 mg/kg/day, respectively. 
 
In a 14 day and 28 day monkey toxicity study, gastro-intestinal (GI) effects (body weight loss, emesis, 
loose/watery faeces, and moderate to severe dehydration) were observed and was the result of local 
drug administration and not systemic toxicity. 
 
In a 3 month study in rats, when cabotegravir was administered by monthly sub-cutaneous (SC) 
injection (up to 100 mg/kg/dose); monthly IM injection (up to 75 mg/kg/dose) or weekly SC injection 
(100 mg/kg/dose), there were no adverse effects noted and no new target organ toxicities (at exposures 
>30 times the exposure in humans at the MRHD of 400 mg IM dose). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Lactose monohydrate 
Microcrystalline cellulose (E460) 
Hypromellose (E464) 
Sodium starch glycolate 
Magnesium stearate 
 
Tablet coating 



42 

 
Hypromellose (E464) 
Titanium dioxide (E171) 
Macrogol (E1521) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
White HDPE (high density polyethylene) bottles closed with polypropylene child-resistant closures, 
with a polyethylene faced induction heat seal liner. Each bottle contains 30 film-coated tablets. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal 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)  
 
EU/1/20/1481/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  
 
 
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. 
 
  

http://www.ema.europa.eu/


43 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

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 

 



44 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Prolonged-release suspension for injection 
Glaxo Operations UK Limited (trading as Glaxo Wellcome Operations) 
Harmire Road  
Barnard Castle  
County Durham DL12 8DT 
UK 
 
GlaxoSmithKline Manufacturing SpA 
Strada Provinciale Asolana, 90 
San Polo di Torrile 
Parma, 43056 
Italy 
 
Film-coated tablets 
Glaxo Wellcome, S.A. 
Avda. Extremadura, 3 
Aranda De Duero 
Burgos 09400 
Spain 
 
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 (PSURs) 
 
The requirements for submission of PSURs 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. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 
6 months following authorisation.  
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (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. 
 



45 

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. 

 
• Additional risk minimisation measures 

 
• Obligation to conduct post-authorisation measures  
 
The MAH shall complete, within the stated timeframe, the below measures: 
 

Description Due date 
The MAH will conduct a prospective cohort study (COMBINE-2 study) to 
collect data from patients in order to assess clinical effectiveness, adherence, 
durability and discontinuations after initiating the cabotegravir and rilpivirine 
long acting regimen. The study will also monitor for resistance and response to 
subsequent antiretroviral regimens among patients who switched from 
cabotegravir and rilpivirine long acting regimen to another regimen The MAH 
will submit interim study results annually and the final results of the study by 
September 2026. 

September 
2026 

The MAH will conduct a real-world five-year Drug Utilisation Study (DUS). 
This observational cohort study will aim to better understand the patient 
population receiving cabotegravir long acting injection and/or rilpivirine long 
acting injection containing regimens in routine clinical practice. The study will 
assess usage patterns, adherence, and post marketing clinical effectiveness of 
these regimens and monitor for resistance among virologic failures for whom 
data on resistance testing are available. The MAH will submit interim study 
results annually and the final results of the DUS by September 2026. 

September 
2026 

 
 
  



46 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



47 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 400 MG INJECTION 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vocabria 400 mg prolonged-release suspension for injection 
cabotegravir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 400 mg cabotegravir. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: mannitol, polysorbate 20, macrogol and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release suspension for injection 
Contents: 1 vial 
1 vial adaptor 
1 syringe 
1 injection needle 
 
2 mL 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Open here 
For intramuscular 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



48 

Do not freeze 
 
 
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/1/20/1481/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
  



49 

PARTICULARS TO APPEAR ON INTERMEDIATE PACKAGING 
 
BACKING CARD - 400 MG INJECTION  
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vocabria 400 mg prolonged-release suspension for injection 
cabotegravir  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
2 mL 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the instructions for use before preparing Vocabria 
For intramuscular use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
 
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 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 



50 

 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
  



51 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – 400 MG INJECTION 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vocabria 400 mg prolonged-release suspension for injection 
cabotegravir 
IM 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2 ml 
 
 
6. OTHER 
 
  



52 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 600 MG INJECTION 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vocabria 600 mg prolonged-release suspension for injection 
cabotegravir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
 
Each vial contains 600 mg cabotegravir. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: mannitol, polysorbate 20, macrogol and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release suspension for injection 
Contents: 1 vial 
1 vial adaptor 
1 syringe 
1 injection needle 
 
3 mL 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Open here 
For intramuscular 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 
 
 



53 

9. SPECIAL STORAGE CONDITIONS 
 
Do not freeze 
 
 
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/1/20/1481/003 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 
  



54 

PARTICULARS TO APPEAR ON INTERMEDIATE PACKAGING 
 
BACKING CARD - 600 MG INJECTION 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vocabria 600 mg prolonged-release suspension for injection 
cabotegravir  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
3 mL 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the instructions for use before preparing Vocabria 
For intramuscular use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
 
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 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 



55 

 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



56 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – 600 MG INJECTION 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vocabria 600 mg prolonged-release suspension for injection 
cabotegravir 
IM 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
  



57 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON - TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vocabria 30 mg film-coated tablets 
cabotegravir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 30 mg cabotegravir (as sodium). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate (see package leaflet) 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



58 

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/1/20/1481/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
vocabria 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



59 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL - TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vocabria 30 mg film-coated tablets 
cabotegravir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 30 mg cabotegravir (as sodium). 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 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 
 
 
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 
 



60 

ViiV Healthcare BV 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1481/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 
  



61 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



62 

Package leaflet: Information for the patient 
 

Vocabria 400 mg prolonged-release suspension for injection 
cabotegravir 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how 
to report side effects. 
 
Read all of this leaflet carefully before you start using 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 nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Vocabria is and what it is used for 
2. What you need to know before you are given Vocabria 
3. How Vocabria injections are given 
4. Possible side effects 
5. How to store Vocabria 
6. Contents of the pack and other information 
 
 
1. What Vocabria is and what it is used for 
 
Vocabria injection contains the active ingredient cabotegravir. Cabotegravir belongs to a group of anti-
retroviral medicines called integrase inhibitors (INIs). 
 
Vocabria injection is used to treat HIV (human immunodeficiency virus) infection in adults aged 18 
years and over, who are also receiving another antiretroviral medicine called rilpivirine and whose 
HIV-1 infection is under control. 
 
Vocabria injections do not cure HIV infection; they keep the amount of virus in your body at a low 
level. This helps maintain the number of CD4 cells in your blood. CD4 cells are a type of white blood 
cells that are important in helping your body to fight infection. 
 
Vocabria injection is always given in combination with another injection of an anti-retroviral 
medicine called rilpivirine injection. Refer to the rilpivirine package leaflet for information on that 
medicine. 
 
 
2. What you need to know before you are given Vocabria 
 
Do not receive a Vocabria injection: 
 if you are allergic (hypersensitive) to cabotegravir or any of the other ingredients of this medicine 

(listed in section 6). 
 if you are taking any of these medicines as they may affect the way Vocabria works: 

- carbamazepine, oxcarbazepine, phenytoin, phenobarbital (medicines to treat epilepsy and 
prevent fits). 

- rifampicin or rifapentine (medicines to treat some bacterial infections such as tuberculosis). 
 
  If you think this applies to you, tell your doctor. 
 



63 

Warnings and precautions 
 
Allergic reaction 
Vocabria contains cabotegravir, which is an integrase inhibitor. Other integrase inhibitors can cause a 
serious allergic reaction known as a hypersensitivity reaction. You need to know about important signs 
and symptoms to look out for while you’re receiving Vocabria. 
 
 Read the information in ‘Other possible side effects’ in section 4 of this leaflet. 
 
Liver problems including hepatitis B and/or C 
Tell your doctor if you have or have had problems with your liver, including hepatitis B and/or C. 
Your doctor may evaluate how severe your liver disease is before deciding if you can take Vocabria. 
 
Look out for important symptoms 
Some people taking medicines for HIV infection develop other conditions, which can be serious. 
You need to know about important signs and symptoms to look out for while you’re taking Vocabria. 
These include: 
• symptoms of infections 
• symptoms of liver damage. 
 
 Read the information in section 4 of this leaflet (‘Possible side effects’). 
 
If you get any symptoms of infection or liver damage: 
 
 Tell your doctor immediately. Don’t take other medicines for the infection without your doctor’s 

advice. 
 

Regular appointments are important 
It is important that you attend your planned appointments to receive your Vocabria injection, to 
control your HIV infection, and to stop your illness from getting worse. Talk to your doctor if you are 
thinking about stopping treatment. If you are late receiving your Vocabria injection, or if you stop 
receiving Vocabria, you will need to take other medicines to treat HIV infection and to reduce the risk 
of developing viral resistance. 
 
Vocabria injection is a long acting medication. If you stop treatment, low levels of cabotegravir (the 
active ingredient of Vocabria) can remain in your system for up to 12 months or more after your last 
injection. These low levels of cabotegravir will not protect you against the virus and the virus may 
become resistant. You must start a different HIV treatment within one month of your last Vocabria 
injection if you are having monthly injections, and within two months of your last Vocabria injection if 
you are having injections every two months. 
 
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 can still pass on HIV when receiving 
this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your doctor 
the precautions needed to avoid infecting other people. 
 
Children and adolescents 
This medicine is not for use in children or adolescents less than 18 years of age, because it has not 
been studied in these patients. 
 
Other medicines and Vocabria injection 
Tell your doctor if you are taking, have recently taken or might take any other medicines including 
other medicines bought without a prescription. 
 
Vocabria must not be given with some other medicines. (see ‘Do not receive a Vocabria injection’ 
earlier in section 2). 



64 

 
Some medicines can affect how Vocabria works or make it more likely that you will have side 
effects. Vocabria can also affect how some other medicines work. 
 
Tell your doctor if you are taking: 
 
 rifabutin (to treat some bacterial infections such as tuberculosis). 
 
 Tell your doctor or pharmacist if you are taking this medicine. Your doctor may decide that you 

need extra check-ups. 
 
Pregnancy and breastfeeding  
 
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby: 
 
 Talk to your doctor before receiving a Vocabria injection 
 
Pregnancy 
• Vocabria is not recommended during pregnancy. If needed, your doctor will consider the 

benefit to you and the risk to your baby of receiving Vocabria injections while you're pregnant. If 
you are planning to have a baby, talk to your doctor in advance 

• If you have become pregnant, do not stop attending your appointments to receive a Vocabria 
injection without consulting your doctor. 

 
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 of Vocabria injection can pass into breast milk. However, it is 
possible that cabotegravir may still pass into breast milk for 12 months after the last injection of 
Vocabria. 
 
If you’re breast-feeding, or thinking about breast-feeding: 
 
 Talk to your doctor immediately. 
 
Driving and using machines 
 
Vocabria can make you dizzy and have other side effects that make you less alert. 
 
 Don’t drive or use machines unless you are sure you’re not affected. 
 
 
3. How Vocabria injections are given 
 
You will be given Vocabria as an injection, either once every month or once every 2 months, together 
with another injection of medicine called rilpivirine. Your doctor will advise you of your dosing 
schedule. 
 
A nurse or doctor will give you Vocabria through an injection in the muscle of your buttock 
(intramuscular, or IM, injection). 
 
When you first start treatment with Vocabria 
 
Your doctor will tell you: 

• to take one 30 mg Vocabria tablet and one 25 mg rilpivirine tablet, once a day, for 
approximately one month 



65 

• after that receive monthly or every 2 month injections.  
This first month is called the lead-in period. It allows your doctor to assess whether it’s appropriate to 
proceed with injections.  
 
Injection schedule for monthly dosing 
  

When 

Which 
medicine 

Month 1 (at least 28 days) At Month 2 
following one 
month of tablets. 

 Month 3 onwards 

Vocabria 30 mg tablet once a day  600 mg injection 400 mg injection every 
month 

Rilpivirine 25 mg tablet once a day 900 mg injection 600 mg injection every 
month  

 

Injection Schedule for every 2 month dosing 

Which 
medicine 

When 

Month 1 (at least 28 days) At Month 2 and Month 3 
following one month of tablets 

 Month 5 onwards 

Vocabria 30 mg tablet once a day 600 mg injection 600 mg injection every 2 
months 

Rilpivirine 25 mg tablet once a day 900 mg injection 900 mg injection every 2 
months 

 
If you miss a Vocabria injection 
 
 Contact your doctor immediately to make a new appointment  

 
It is important that you keep your regular planned appointments to receive your injection to control 
your HIV and to stop your illness from getting worse. Talk to your doctor if you are thinking about 
stopping treatment.  
 
Talk to your doctor if you think you will not be able to receive your Vocabria injection at the usual 
time. Your doctor may recommend you take Vocabria tablets instead, until you are able to receive 
Vocabria injection again. 
 
If you are given too much Vocabria injection 
A doctor or nurse will give this medicine to you, so it is unlikely that you will be given too much. If 
you are worried, tell the doctor or nurse. 
 
Don’t stop receiving Vocabria injections without advice from your doctor. 
Keep receiving Vocabria injections for as long as your doctor recommends. Don’t stop unless your 
doctor advises you to. If you stop, your doctor must start you on another HIV treatment within a month 
of your last Vocabria injection if you are having monthly injections, and within two months of your 
last Vocabria injection if you are having injections every two months, to reduce the risk of developing 
viral resistance. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 



66 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Very common side effects 
These may affect more than 1 in 10 people: 

• headache 
• injection site reactions. In clinical studies, these were generally mild to moderate and became 

less frequent over time. Symptoms may include: 
o very common: pain and discomfort, a hardened mass or lump 
o common: redness, itching, swelling, bruising, warmth or discolouration, which may 

include a collection of blood under the skin 
o uncommon: numbness, minor bleeding, an abscess (collection of pus) or cellulitis 

(heat, swelling or redness). 
• feeling hot (pyrexia). 

 
Common side effects 
These may affect up to 1 in 10 people: 

• depression 
• anxiety 
• abnormal dreams 
• difficulty in sleeping (insomnia) 
• dizziness 
• feeling sick (nausea)  
• vomiting 
• stomach pain (abdominal pain) 
• wind (flatulence) 
• diarrhoea 
• rash 
• muscle pain (myalgia) 
• lack of energy (fatigue) 
• feeling weak (asthenia) 
• generally feeling unwell (malaise) 
• weight gain. 

 
Uncommon side effects 
These may affect up to 1 in 100 people: 

• feeling drowsy (somnolence) 
• feeling lightheaded, during or following an injection. This may lead to fainting 
• liver damage (signs may include yellowing of the skin and the whites of the eyes, loss of 

appetite, itching, tenderness of the stomach, light-coloured stools or unusually dark urine) 
• changes in liver blood tests (increase in transaminases or increase in bilirubin). 

 
Other side effects that may show up in blood tests 

• an increase in lipases (a substance produced by the pancreas) 
 
Other possible side effects 
 
People receiving Vocabria and rilpivirine therapy for HIV may get other side effects. 
 
Allergic reactions 
 
Vocabria contains cabotegravir, which is an integrase inhibitor. Other integrase inhibitors can cause a 
serious allergic reaction known as a hypersensitivity reaction, although this has not been seen with 
Vocabria. 
 



67 

If you get any of the following symptoms: 
• skin rash 
• a high temperature (fever) 
• lack of energy (fatigue) 
• swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
• muscle or joint aches. 

 
 See a doctor straight away. Your doctor may decide to carry out tests to check your liver, kidneys 

or blood, and may tell you to stop taking Vocabria. 
 
Pancreatitis 
 
If you get severe pain in the abdomen (tummy), this may be caused by inflammation of your pancreas 
(pancreatitis). 
 
  Tell your doctor, especially if the pain spreads and gets worse. 
 
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 and/or muscle pain 
• joint pain or swelling 
• 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: 
 
  Tell your doctor immediately. Don’t take other medicines for the infection without your doctor’s 

advice. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. 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 Vocabria 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
This medicine does not require any special temperature storage conditions. 

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


68 

 
Do not freeze. 
 
 
6. Contents of the pack and other information 
 
What Vocabria contains  
- The active substance is cabotegravir. 
 
Each 2 ml vial contains 400 mg cabotegravir. 
 
The other ingredients are:  
Mannitol (E421) 
Polysorbate 20 (E432) 
Macrogol (E1521) 
Water for injections 
 
What Vocabria looks like and contents of the pack 
Cabotegravir prolonged release suspension for injection is presented in a brown glass vial with a 
rubber stopper. The pack also contains 1 syringe, 1 vial adaptor, and 1 injection needle. 
 
Marketing Authorisation Holder 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H,  
3811 LP Amersfoort  
Netherlands 
 
Manufacturer 
Glaxo Operations UK Limited (trading as Glaxo Wellcome Operations) 
Harmire Road 
Barnard Castle 
County Durham DL12 8DT 
UK 
 
GlaxoSmithKline Manufacturing SpA 
Strada Provinciale Asolana, 90 
San Polo di Torrile 
Parma, 43056 
Italy 
 
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 

mailto:info.lt@gsk.com


69 

 
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 69 69 
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 

 
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 7741600 

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

 
Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 397000 
gskcyprus@gsk.com 

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

 
Latvija 

 
United Kingdom 

mailto:viiv.med.info@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com


70 

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

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

  
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
------------------------------------------------------------------------------------------------------------------------ 
  



71 

The following information is intended for healthcare professionals only: 
 
Vocabria 2 mL injection Instructions for use: 

Overview 
A complete dose requires two injections: VOCABRIA and rilpivirine 
2 mL of cabotegravir and 2 mL of rilpivirine. 
Cabotegravir and rilpivirine are suspensions that do not need further dilution or reconstitution. The 
preparation steps for both medicines are the same. 
Cabotegravir and rilpivirine are for intramuscular use only. Both injections must be administered to the 
gluteal sites. The administration order is not important. 

Note: The ventrogluteal site is recommended. 
 

 Storage information 

• This medicine does not require any special storage conditions. 
Do not freeze.  

 

 
 

Your pack contains 
• 1 vial of cabotegravir 
• 1 vial adaptor 
• 1 syringe 
• 1 injection needle (0.65 mm, 38 mm [23 gauge, 1.5 inches]) 

 
Consider the patient’s build and use medical judgment to select an appropriate injection needle 
length. 

2 mL 

2 mL 

Cabotegravir vial Vial adaptor 

Vial cap 
(Rubber 
stopper 
under cap) 

Syringe 

Plunger 

Injection needle 

Needle guard 

Needle cap 



72 

You will also need 

• Non-sterile gloves 
• 2 alcohol swabs 
• 2 gauze pads 
• A suitable sharps container 
• 1 rilpivirine 2 mL pack 
Make sure to have the rilpivirine pack close by before starting. 

 
Preparation 
1. Inspect vial 

 

• Check that the expiry date has not passed. 
• Inspect the vial immediately. If you can see 

foreign matter, do not use the product. 
 

Note: The Cabotegravir vial has a brown tint 
to the glass. 
Do not use if the expiry date has passed. 

2. Wait 15 minutes 

 

• If the pack has been stored in a fridge, 
remove and wait at least 15 minutes before 
you are ready to give the injection to allow 
the medicine to come to room temperature. 

3. Shake vigorously 

 

• Hold the vial firmly and vigorously shake for 
a full 10 seconds as shown. 

• Invert the vial and check the resuspension. It 
should look uniform. If the suspension is not 
uniform, shake the vial again. 

• It is also normal to see small air bubbles. 

Check expiry date 
and medicine 

E
X

P 

M
O

N
T

H
/Y

E
A

R
 

Wait 15 minutes 

10 
secs 



73 

4. Remove vial cap 

 

• Remove the cap from the vial. 
• Wipe the rubber stopper with an alcohol 

swab. 
 

Do not allow anything to touch the rubber 
stopper after wiping it. 

 

5. Peel open vial adaptor 

 

• Peel off the paper backing from the vial 
adaptor packaging. 

 
Note: Keep the adaptor in place in its 
packaging for the next step.  

 

6. Attach vial adaptor 

 

• Press the vial adaptor straight down onto the 
vial using the packaging, as shown. 
The vial adaptor should snap securely into 
place. 

• When you are ready, lift off the vial adaptor 
packaging as shown. 

7. Prepare syringe 

 

• Remove the syringe from its packaging. 
• Draw 1 mL of air into the syringe. This will 

make it easier to draw up the liquid later. 



74 

8. Attach syringe 

 

• Hold the vial adaptor and vial firmly, as 
shown. 

• Screw the syringe firmly onto the vial adaptor. 
• Press the plunger all the way down to push the 

air into the vial. 

9. Slowly draw up dose 

 

• Invert the syringe and vial, and slowly 
withdraw as much of the liquid as possible 
into the syringe. There might be more liquid 
than the dose amount. 

 

10. Unscrew syringe 

 

• Screw the syringe off the vial adaptor, holding 
the vial adaptor as shown. 
 
Note: Keep the syringe upright to avoid 
leakage. Check that the cabotegravir 
suspension looks uniform and white to light 
pink. 

11. Attach needle 

 

• Peel open the needle packaging part way to 
expose the needle base. 

• Keeping the syringe upright, firmly twist the 
syringe onto the needle. 

• Remove the needle packaging from the 
needle. 



75 

Injection 
12. Prepare injection site 

 

Injections must be administered to the gluteal 
sites. Select from the following areas for the 
injection: 
• Ventrogluteal (recommended) 
• Dorsogluteal (upper outer quadrant) 

Note: For gluteal intramuscular use only. 
Do not inject intravenously. 

13. Remove cap 

 

• Fold the needle guard away from the needle. 
• Pull off the injection needle cap. 

14. Remove extra liquid 

 

• Hold the syringe with the needle pointing up. 
Press the plunger to the 2 mL dose to remove 
extra liquid and any air bubbles. 
 
Note: Clean the injection site with an alcohol 
swab. Allow the skin to air dry before 
continuing. 

15. Stretch skin 
 Use the z-track injection technique to minimise 

medicine leakage from the injection site. 
 
• Firmly drag the skin covering the injection 

site, displacing it by about an inch (2.5 cm). 
• Keep it held in this position for the injection. 

2 mL 

1 inch 
(2.5 cm) 

Ventrogluteal Dorsogluteal 



76 

16. Insert needle 

 

• Insert the needle to its full depth, or deep 
enough to reach the muscle. 

17. Inject dose 

 

• Still holding the skin stretched – slowly press 
the plunger all the way down. 

• Ensure the syringe is empty. 
• Withdraw the needle and release the stretched 

skin immediately. 

18. Assess the injection site 

 

• Apply pressure to the injection site using a 
gauze. 

• A small bandage may be used if a bleed 
occurs. 

 
Do not massage the area. 

19. Make needle safe 

 

• Fold the needle guard over the needle. 
• Gently apply pressure using a hard surface to 

lock the needle guard in place. 
• The needle guard will make a click when it 

locks.  

click 



77 

After injection 
20. Dispose safely 

 

• Dispose of used needles, syringes, vials and 
vial adaptors according to local health and 
safety laws. 

Repeat for 2nd medicine 
 If you have not yet injected both medicines, 

use the steps for preparation and injection 
for rilpivirine which has its own specific 
Instructions for Use. 

Questions and Answers 

1. How long can the medicine be left in the syringe? 

Once the suspension has been drawn into the syringe, the injection should be used immediately, from a 
microbiological point of view. 

Chemical and physical in-use stability has been demonstrated for 2 hours at 25°C. 

2. Why do I need to inject air into the vial? 

Injecting 1 mL of air into the vial makes it easier to draw up the dose into the syringe. 

Without the air, some liquid may flow back into the vial unintentionally, leaving less than intended in 
the syringe. 

3. Does the order in which I give the medicines matter? 

No, the order is unimportant. 

4. If the pack has been stored in the fridge, is it safe to warm the vial up to room temperature 
more quickly? 

It is best to let the vial come to room temperature naturally. However, you can use the warmth of your 
hands to speed up the warm up time, but make sure the vial does not get above 30°C. 

Do not use any other heating methods. 

5. Why is the ventrogluteal administration approach recommended? 
The ventrogluteal approach, into the gluteus medius muscle, is recommended because it is located away 
from major nerves and blood vessels. A dorso-gluteal approach, into the gluteus maximus muscle, is 
acceptable, if preferred by the health care professional. The injection should not be administered in any 
other site. 

Repeat all steps 
for 2nd medicine 



78 

 
Package leaflet: Information for the patient 

 
Vocabria 600 mg prolonged-release suspension for injection 

cabotegravir 
 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 
information. You can help by reporting any side effects you may get. See the end of section 4 for how 
to report side effects. 
 
Read all of this leaflet carefully before you start using 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 nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Vocabria is and what it is used for 
2. What you need to know before you are given Vocabria 
3. How Vocabria injections are given 
4. Possible side effects 
5. How to store Vocabria 
6. Contents of the pack and other information 
 
 
1. What Vocabria is and what it is used for 
 
Vocabria injection contains the active ingredient cabotegravir. Cabotegravir belongs to a group of anti-
retroviral medicines called integrase inhibitors (INIs). 
 
Vocabria injection is used to treat HIV (human immunodeficiency virus) infection in adults aged 18 
years and over, who are also receiving another antiretroviral medicine called rilpivirine and whose 
HIV-1 infection is under control. 
 
Vocabria injections do not cure HIV infection; they keep the amount of virus in your body at a low 
level. This helps maintain the number of CD4 cells in your blood. CD4 cells are a type of white blood 
cells that are important in helping your body to fight infection. 
 
Vocabria injection is always given in combination with another injection of an anti-retroviral 
medicine called rilpivirine injection. Refer to the rilpivirine package leaflet for information on that 
medicine. 
 
 
2. What you need to know before you are given Vocabria 
 
Do not receive a Vocabria injection: 
 if you are allergic (hypersensitive) to cabotegravir or any of the other ingredients of this medicine 

(listed in section 6). 
 if you are taking any of these medicines as they may affect the way Vocabria works: 

- carbamazepine, oxcarbazepine, phenytoin, phenobarbital (medicines to treat epilepsy and 
prevent fits). 

- rifampicin or rifapentine (medicines to treat some bacterial infections such as tuberculosis). 
 
  If you think this applies to you, tell your doctor. 
 



79 

Warnings and precautions 
 
Allergic reaction 
Vocabria contains cabotegravir, which is an integrase inhibitor. Other integrase inhibitors can cause a 
serious allergic reaction known as a hypersensitivity reaction. You need to know about important signs 
and symptoms to look out for while you’re receiving Vocabria. 
 
 Read the information in ‘Other possible side effects’ in section 4 of this leaflet. 
 
Liver problems including hepatitis B and/or C 
Tell your doctor if you have or have had problems with your liver, including hepatitis B and/or C. 
Your doctor may evaluate how severe your liver disease is before deciding if you can take Vocabria. 
 
Look out for important symptoms 
Some people taking medicines for HIV infection develop other conditions, which can be serious. 
You need to know about important signs and symptoms to look out for while you’re taking Vocabria. 
These include: 
• symptoms of infections 
• symptoms of liver damage. 
 
 Read the information in section 4 of this leaflet (‘Possible side effects’). 
 
If you get any symptoms of infection or liver damage: 
 
 Tell your doctor immediately. Don’t take other medicines for the infection without your doctor’s 

advice. 
 

Regular appointments are important 
 
It is important that you attend your planned appointments to receive your Vocabria injection, to 
control your HIV infection, and to stop your illness from getting worse. Talk to your doctor if you are 
thinking about stopping treatment. If you are late receiving your Vocabria injection, or if you stop 
receiving Vocabria, you will need to take other medicines to treat HIV infection and to reduce the risk 
of developing viral resistance. 
 
Vocabria injection is a long acting medication. If you stop treatment, low levels of cabotegravir (the 
active ingredient of Vocabria) can remain in your system for up to 12 months or more after your last 
injection. These low levels of cabotegravir will not protect you against the virus and the virus may 
become resistant. You must start a different HIV treatment within one month of your last Vocabria 
injection if you are having monthly injections, and within two months of your last Vocabria injection if 
you are having injections every two months. 
 
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 can still pass on HIV when receiving 
this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your doctor 
the precautions needed to avoid infecting other people. 
 
Children and adolescents 
This medicine is not for use in children or adolescents less than 18 years of age, because it has not 
been studied in these patients. 
 
Other medicines and Vocabria injection 
Tell your doctor if you are taking, have recently taken or might take any other medicines including 
other medicines bought without a prescription. 
 



80 

Vocabria must not be given with some other medicines. (see ‘Do not receive a Vocabria injection’ 
earlier in section 2). 
 
Some medicines can affect how Vocabria works or make it more likely that you will have side 
effects. Vocabria can also affect how some other medicines work. 
 
Tell your doctor if you are taking: 
 
 rifabutin (to treat some bacterial infections such as tuberculosis). 
 
 Tell your doctor or pharmacist if you are taking this medicine. Your doctor may decide that you 

need extra check-ups. 
 
Pregnancy and breastfeeding  
 
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby: 
 
 Talk to your doctor before receiving a Vocabria injection 
 
Pregnancy 
• Vocabria is not recommended during pregnancy. If needed, your doctor will consider the 

benefit to you and the risk to your baby of receiving Vocabria injections while you're pregnant. If 
you are planning to have a baby, talk to your doctor in advance 

• If you have become pregnant, do not stop attending your appointments to receive a Vocabria 
injection without consulting your doctor. 

 
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 of Vocabria injection can pass into breast milk. However, it is 
possible that cabotegravir may still pass into breast milk for 12 months after the last injection of 
Vocabria. 
 
If you’re breast-feeding, or thinking about breast-feeding: 
 
 Talk to your doctor immediately. 
 
Driving and using machines 
 
Vocabria can make you dizzy and have other side effects that make you less alert. 
 
 Don’t drive or use machines unless you are sure you’re not affected. 
 
 
3. How Vocabria injections are given 
 
You will be given Vocabria as an injection, either once every month or once every 2 months, together 
with another injection of medicine called rilpivirine. Your doctor will advise you of your dosing 
schedule. 
 
A nurse or doctor will give you Vocabria through an injection in the muscle of your buttock 
(intramuscular, or IM, injection). 
 
When you first start treatment with Vocabria 
 
Your doctor will tell you: 



81 

• to take one 30 mg Vocabria tablet and one 25 mg rilpivirine tablet, once a day, for 
approximately one month 

• after that receive monthly or every 2 month injections. 
This first month is called the lead-in period. It allows your doctor to assess whether it’s appropriate to 
proceed with injections. 
 
Injection schedule for monthly dosing 
  

When 

Which 
medicine 

Month 1 (at least 28 days) At Month 2 
following one 
month of tablets. 

 Month 3 onwards 

Vocabria 30 mg tablet once a day  600 mg injection 400 mg injection every 
month 

Rilpivirine 25 mg tablet once a day 900 mg injection 600 mg injection every 
month  

 
Injection Schedule for every 2 month dosing 
 
Which 
medicine 

When 

Month 1 (at least 28 days) At Month 2 and Month 3 
following one month of 
tablets 

 Month 5 onwards 

Vocabria 30 mg tablet once a day 600 mg injection 600 mg injection 
every 2 months 

Rilpivirine 25 mg tablet once a day 900 mg injection 900 mg injection 
every 2 months  

 
If you miss a Vocabria injection 
 
 Contact your doctor immediately to make a new appointment  

 
It is important that you keep your regular planned appointments to receive your injection to control 
your HIV and to stop your illness from getting worse. Talk to your doctor if you are thinking about 
stopping treatment.  
 
Talk to your doctor if you think you will not be able to receive your Vocabria injection at the usual 
time. Your doctor may recommend you take Vocabria tablets instead, until you are able to receive 
Vocabria injection again. 
 
If you are given too much Vocabria injection 
A doctor or nurse will give this medicine to you, so it is unlikely that you will be given too much. If 
you are worried, tell the doctor or nurse. 
 
Don’t stop receiving Vocabria injections without advice from your doctor. 
Keep receiving Vocabria injections for as long as your doctor recommends. Don’t stop unless your 
doctor advises you to. If you stop, your doctor must start you on another HIV treatment within a month 
of your last Vocabria injection if you are having monthly injections, and within two months of your 
last Vocabria injection if you are having injections every two months, to reduce the risk of developing 
viral resistance. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 



82 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Very common side effects 
These may affect more than 1 in 10 people: 

• headache 
• injection site reactions. In clinical studies, these were generally mild to moderate and became 

less frequent over time. Symptoms may include: 
o very common: pain and discomfort, a hardened mass or lump 
o common: redness, itching, swelling, bruising, warmth or discolouration, which may 

include a collection of blood under the skin 
o uncommon: numbness, minor bleeding, an abscess (collection of pus) or cellulitis 

(heat, swelling or redness). 
• feeling hot (pyrexia). 

 
Common side effects 
These may affect up to 1 in 10 people: 

• depression 
• anxiety 
• abnormal dreams 
• difficulty in sleeping (insomnia) 
• dizziness 
• feeling sick (nausea)  
• vomiting 
• stomach pain (abdominal pain) 
• wind (flatulence) 
• diarrhoea 
• rash 
• muscle pain (myalgia) 
• lack of energy (fatigue) 
• feeling weak (asthenia) 
• generally feeling unwell (malaise) 
• weight gain. 

 
Uncommon side effects 
These may affect up to 1 in 100 people: 

• feeling drowsy (somnolence) 
• feeling lightheaded, during or following an injection. This may lead to fainting 
• liver damage (signs may include yellowing of the skin and the whites of the eyes, loss of 

appetite, itching, tenderness of the stomach, light-coloured stools or unusually dark urine) 
• changes in liver blood tests (increase in transaminases or increase in bilirubin). 

 
Other side effects that may show up in blood tests 

• an increase in lipases (a substance produced by the pancreas) 
 
Other possible side effects 
 
People receiving Vocabria and rilpivirine therapy for HIV may get other side effects. 
 
Allergic reactions 
 
Vocabria contains cabotegravir, which is an integrase inhibitor. Other integrase inhibitors can cause a 
serious allergic reaction known as a hypersensitivity reaction, although this has not been seen with 
Vocabria. 
 



83 

If you get any of the following symptoms: 
• skin rash 
• a high temperature (fever) 
• lack of energy (fatigue) 
• swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
• muscle or joint aches. 

 
 See a doctor straight away. Your doctor may decide to carry out tests to check your liver, kidneys 

or blood, and may tell you to stop taking Vocabria. 
 
Pancreatitis 
 
If you get severe pain in the abdomen (tummy), this may be caused by inflammation of your pancreas 
(pancreatitis). 
 
  Tell your doctor, especially if the pain spreads and gets worse. 
 
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 and/or muscle pain 
• joint pain or swelling 
• 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: 
 
  Tell your doctor immediately. Don’t take other medicines for the infection without your doctor’s 

advice. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. 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 Vocabria 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
This medicine does not require any special temperature storage conditions. 

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


84 

 
Do not freeze. 
 
 
6. Contents of the pack and other information 
 
What Vocabria contains  
- The active substance is cabotegravir. 
 
Each 3 ml vial contains 600 mg cabotegravir. 
 
The other ingredients are:  
Mannitol (E421) 
Polysorbate 20 (E432) 
Macrogol (E1521) 
Water for injections 
 
What Vocabria looks like and contents of the pack 
Cabotegravir prolonged release suspension for injection is presented in a brown glass vial with a 
rubber stopper. The pack also contains 1 syringe, 1 vial adaptor, and 1 injection needle. 
 
Marketing Authorisation Holder 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H,  
3811 LP Amersfoort  
Netherlands 
 
Manufacturer 
Glaxo Operations UK Limited (trading as Glaxo Wellcome Operations) 
Harmire Road 
Barnard Castle 
County Durham DL12 8DT 
UK 
 
GlaxoSmithKline Manufacturing SpA 
Strada Provinciale Asolana, 90 
San Polo di Torrile 
Parma, 43056 
Italy 
 
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 

mailto:info.lt@gsk.com


85 

 
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 69 69 
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 

 
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 7741600 

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

 
Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 397000 
gskcyprus@gsk.com 

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

mailto:viiv.med.info@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com


86 

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

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

  
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
------------------------------------------------------------------------------------------------------------------------ 



87 

The following information is intended for healthcare professionals only: 
 
Vocabria 3 mL injection Instructions for use: 
 
Overview 
A complete dose requires two injections: VOCABRIA and rilpivirine 
3 mL of cabotegravir and 3 mL of rilpivirine. 
Cabotegravir and rilpivirine are suspensions that do not need further dilution or reconstitution. The 
preparation steps for both medicines are the same. 
Cabotegravir and rilpivirine are for intramuscular use only. Both injections must be administered to the 
gluteal sites. The administration order is not important. 

Note: The ventrogluteal site is recommended. 
 

 Storage information 

• This medicine does not require any special storage conditions. 
Do not freeze.  

 

 
 

Your pack contains 

• 1 vial of cabotegravir 
• 1 vial adaptor 
• 1 syringe 
• 1 injection needle (0.65 mm, 38 mm [23 gauge, 1.5 inches]) 

 
Consider the patient’s build and use medical judgment to select an appropriate injection needle 
length. 

2 mL 

2 mL 

Cabotegravir vial Vial adaptor 

Vial cap 
(Rubber 
stopper 
under cap) 

Syringe 

Plunger 

Injection needle 

Needle guard 

Needle cap 



88 

You will also need 

• Non-sterile gloves 
• 2 alcohol swabs 
• 2 gauze pads 
• A suitable sharps container 
• 1 rilpivirine 3 mL pack 

Make sure to have the rilpivirine pack close by before starting. 

 
Preparation 
1. Inspect vial 

 

• Check that the expiry date has not passed. 
• Inspect the vial immediately. If you can see 

foreign matter, do not use the product. 
 

Note: The cabotegravir vial has a brown tint 
to the glass. 
Do not use if the expiry date has passed. 

2. Wait 15 minutes 

 

• If the pack has been stored in a fridge, 
remove and wait at least 15 minutes before 
you are ready to give the injection to allow 
the medicine to come to room temperature. 

3. Shake vigorously 
 • Hold the vial firmly and vigorously shake for 

a full 10 seconds as shown. 
• Invert the vial and check the resuspension. It 

should look uniform. If the suspension is not 
uniform, shake the vial again. 

• It is also normal to see small air bubbles. 

Check expiry 
date and 

 

E
X

P 

M
O

N
T

H
/Y

E
A

Wait 15 minutes 

10 
secs 



89 

4. Remove vial cap 

 

• Remove the cap from the vial. 
• Wipe the rubber stopper with an alcohol 

swab. 
 

Do not allow anything to touch the rubber 
stopper after wiping it. 

 

5. Peel open vial adaptor 

 

• Peel off the paper backing from the vial 
adaptor packaging. 

 
Note: Keep the adaptor in place in its 
packaging for the next step.  

 

6. Attach vial adaptor 

 

• Press the vial adaptor straight down onto the 
vial using the packaging, as shown. 
The vial adaptor should snap securely into 
place. 

• When you are ready, lift off the vial adaptor 
packaging as shown. 

7. Prepare syringe 
 • Remove the syringe from its packaging. 

• Draw 1 mL of air into the syringe. This will 
make it easier to draw up the liquid later. 



90 

8. Attach syringe 

 

• Hold the vial adaptor and vial firmly, as 
shown. 

• Screw the syringe firmly onto the vial adaptor. 
• Press the plunger all the way down to push the 

air into the vial. 

9. Slowly draw up dose 

 

• Invert the syringe and vial, and slowly 
withdraw as much of the liquid as possible 
into the syringe. There might be more liquid 
than the dose amount. 

 

10. Unscrew syringe 

 

• Screw the syringe off the vial adaptor, holding 
the vial adaptor as shown. 
 
Note: Keep the syringe upright to avoid 
leakage. Check that the cabotegravir 
suspension looks uniform and white to light 
pink. 

11. Attach needle 

 

• Peel open the needle packaging part way to 
expose the needle base. 

• Keeping the syringe upright, firmly twist the 
syringe onto the needle. 

• Remove the needle packaging from the 
needle. 



91 

Injection 
12. Prepare injection site 
 Injections must be administered to the gluteal 

sites. 
Select from the following areas for the injection: 
• Ventrogluteal (recommended) 
• Dorsogluteal (upper outer quadrant) 

Note: For gluteal intramuscular use only. 
Do not inject intravenously. 

13. Remove cap 

 

• Fold the needle guard away from the needle. 
• Pull off the injection needle cap. 

14. Remove extra liquid 

 

• Hold the syringe with the needle pointing up. 
Press the plunger to the 3 mL dose to remove 
extra liquid and any air bubbles. 
 
Note: Clean the injection site with an alcohol 
swab. Allow the skin to air dry before 
continuing. 

15. Stretch skin 

 

Use the z-track injection technique to minimise 
medicine leakage from the injection site. 
 
• Firmly drag the skin covering the injection 

site, displacing it by about an inch (2.5 cm). 
• Keep it held in this position for the injection. 

Ventrogluteal Dorsogluteal 

3 mL 

1 inch 
(2.5 cm) 



92 

16. Insert needle 

 

• Insert the needle to its full depth, or deep 
enough to reach the muscle. 

17. Inject dose 

 

• Still holding the skin stretched – slowly press 
the plunger all the way down. 

• Ensure the syringe is empty. 
• Withdraw the needle and release the stretched 

skin immediately. 

18. Assess the injection site 

 

• Apply pressure to the injection site using a 
gauze. 

• A small bandage may be used if a bleed 
occurs. 

 
Do not massage the area. 

19. Make needle safe 

 

• Fold the needle guard over the needle. 
• Gently apply pressure using a hard surface to 

lock the needle guard in place. 
• The needle guard will make a click when it 

locks. 

click 



93 

After injection 
20. Dispose safely 

 

• Dispose of used needles, syringes, vials and 
vial adaptors according to local health and 
safety laws. 

Repeat for 2nd medicine 
 If you have not yet injected both medicines, 

use the steps for preparation and injection 
for Rilpivirine which has its own specific 
Instructions for Use. 

Questions and Answers 

1. How long can the medicine be left in the syringe? 

Once the suspension has been drawn into the syringe, the injection should be used immediately, from a 
microbiological point of view. 

Chemical and physical in-use stability has been demonstrated for 2 hours at 25°C. 

2. Why do I need to inject air into the vial? 

Injecting 1 mL of air into the vial makes it easier to draw up the dose into the syringe. 

Without the air, some liquid may flow back into the vial unintentionally, leaving less than intended in 
the syringe. 

3. Does the order in which I give the medicines matter? 

No, the order is unimportant. 

4. If the pack has been stored in the fridge, is it safe to warm the vial up to room temperature 
more quickly? 

It is best to let the vial come to room temperature naturally. However, you can use the warmth of your 
hands to speed up the warm up time, but make sure the vial does not get above 30°C. 

Do not use any other heating methods. 

5. Why is the ventrogluteal administration approach recommended? 
The ventrogluteal approach, into the gluteus medius muscle, is recommended because it is located away 
from major nerves and blood vessels. A dorso-gluteal approach, into the gluteus maximus muscle, is 
acceptable, if preferred by the health care professional. The injection should not be administered in any 
other site. 

Repeat all steps 
for 2nd medicine 



94 

Package leaflet: Information for the patient 
 

Vocabria 30 mg film-coated tablets 
cabotegravir 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how 
to report side effects. 
 
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 Vocabria tablets are and what they are used for 
2. What you need to know before you take Vocabria tablets 
3. How to take Vocabria tablets 
4. Possible side effects  
5. How to store Vocabria tablets 
6. Contents of the pack and other information 
 
 
1. What Vocabria is and what it is used for 
 
Vocabria tablets contain the active ingredient cabotegravir. Cabotegravir belongs to a group of anti-
retroviral medicines called integrase inhibitors (INIs). 
 
Vocabria tablets are used to treat HIV (human immunodeficiency virus) infection in adults aged 18 
years and over who are also taking another antiretroviral medicine called rilpivirine and whose HIV-1 
infection is under control.  
 
Vocabria tablets do not cure HIV infection; they keep the amount of virus in your body at a low level. 
This helps maintain the number of CD4+ cells in your blood. CD4+ cells are a type of white blood 
cells that are important in helping your body to fight infection. 
 
Your doctor will advise you to take Vocabria tablets before you are given a Vocabria injection for the 
first time.  
 
If you are being given Vocabria injection, but you are not able to receive your injection, your doctor 
may also recommend that you take Vocabria tablets instead, until you can receive the injection again. 
 
Vocabria tablets are always given in combination with another anti-retroviral medicine called 
rilpivirine tablets to treat HIV infection. Vocabria and rilpivirine tablets will replace your current 
antiretroviral medicines. Refer to the rilpivirine package leaflet for information on that medicine. 
 
 
2. What you need to know before you take Vocabria 
 
Do not take Vocabria tablets: 
- - if you are allergic (hypersensitive) to cabotegravir or any of the other ingredients of this 

medicine (listed in section 6). 



95 

- if you are taking any of these medicines, as they may affect the way Vocabria works: 
 
- carbamazepine, oxcarbazepine, phenytoin, phenobarbital (medicines to treat epilepsy and 

prevent fits) 
- rifampicin or rifapentine (medicines to treat some bacterial infections such as tuberculosis). 

 
  If you think this applies to you, tell your doctor. 
 
Warnings and precautions 
 
Allergic reaction 
Vocabria contains cabotegravir, which is an integrase inhibitor. Other integrase inhibitors can cause a 
serious allergic reaction known as a hypersensitivity reaction. You need to know about important signs 
and symptoms to look out for while you’re taking Vocabria. 
 
 Read the information in ‘Other possible side effects’ in section 4 of this leaflet. 
 
Liver problems including hepatitis B and/or C 
Tell your doctor if you have or have had problems with your liver, including hepatitis B and/or C. 
Your doctor may evaluate how severe your liver disease is before deciding if you can take Vocabria. 
 
Look out for important symptoms 
Some people taking medicines for HIV infection develop other conditions, which can be serious. You 
need to know about important signs and symptoms to look out for while you’re taking Vocabria. These 
include: 
• symptoms of infections 
• symptoms of liver damage. 

 
 Read the information in section 4 of this leaflet (‘Possible side effects’). 

 
If you get any symptoms of infection or liver damage: 
 
 Tell your doctor immediately. Don’t take other medicines for the infection without your doctor’s 

advice. 
 
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 can still pass on HIV when taking this 
medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your doctor the 
precautions needed to avoid infecting other people. 
 
Children and adolescents 
This medicine is not for use in children or adolescents less than 18 years of age, because it has not 
been studied in these patients. 
 
Other medicines and Vocabria tablets 
Tell your doctor if you are taking, have recently taken or might take any other medicines including 
other medicines bought without a prescription. 
 
Vocabria must not be taken with some other medicines (see ‘Do not take Vocabria tablets’ earlier in 
section 2): 
 
Some medicines can affect how Vocabria works or make it more likely that you will have side 
effects. Vocabria can also affect how some other medicines work. 
 
Tell your doctor if you are taking any of the medicines in the following list: 
 



96 

• Medicines called antacids, to treat indigestion and heartburn. Antacids can stop the medicine 
in Vocabria tablets from being absorbed into your body. 
Do not take these medicines in the 2 hours before you take Vocabria or for at least 4 hours after 
you take it. 

• rifabutin (to treat some bacterial injections such as tuberculosis).  
 

 Tell your doctor or pharmacist if you are taking any of these. Your doctor may decide that you 
need extra check-ups. 

 
Pregnancy and breastfeeding 
 
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby: 
 
 Talk to your doctor before taking Vocabria . 
 
Pregnancy 
• Vocabria is not recommended during pregnancy. If needed, your doctor will consider the 

benefit to you and the risk to your baby of taking Vocabria while you're pregnant. If you are 
planning to have a baby, talk to your doctor in advance 

• If you have become pregnant do not stop taking Vocabria without consulting your doctor. 
 
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 of Vocabria tablets can pass into breast milk. 
 
If you’re breast-feeding, or thinking about breast-feeding: 
 
 Talk to your doctor immediately. 
 
Driving and using machines 
 
Vocabria can make you dizzy and have other side effects that make you less alert. 
 
 Don’t drive or use machines unless you are sure you’re not affected. 
 
Important information about some of the ingredients of Vocabria 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-

free’. 
 
 
3. How to take Vocabria 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
Vocabria tablets must always be taken with another HIV medicine (rilpivirine tablets). You should 
also follow the instructions for rilpivirine carefully. The leaflet is supplied in the rilpivirine carton. 
 
Dosing schedule for Vocabria tablets followed by monthly injections 
 



97 

Which medicine When 

During month 1 (at 
least 28 days) 

At month 2 following 
one month of tablets 

 Month 3 onwards 

Vocabria 30 mg tablet once 
daily 

600 mg injection 400 mg injection 
monthly 

Rilpivirine 25 mg tablet once 
daily 

900 mg injection 600 mg injection 
monthly 

 
Dosing schedule for Vocabria tablets followed by every 2 month injections 
 

Which 
medicine 

When 

Month 1 (at least 28 days) At Month 2 and Month 
3 following one month 
of tablets 

 Month 5 onwards 

Vocabria 30 mg tablet once a day 600 mg injection 600 mg injection 
every 2 months 

Rilpivirine 25 mg tablet once a day 900 mg injection 900 mg injection 
every 2 months  

 
When you first start treatment with Vocabria 
Your doctor will tell you: 
 to take one 30 mg Vocabria tablet and one 25 mg rilpivirine tablet, once a day, for approximately 

one month.  
 after that, receive monthly or every 2 month injections. 
The first month is called the lead-in-period. It allows your doctor to assess whether it’s appropriate to 
proceed with injections. 
 
How to take the tablets 
Vocabria tablets should be swallowed with a small amount of water.  
 
Vocabria can be taken with or without food. However, when Vocabria is taken at the same time as 
rilpivirine, both tablets should be taken with a meal. 
 
If you cannot receive your Vocabria injection 
If you are not able to receive your Vocabria injection, your doctor may recommend you take Vocabria 
tablets instead, until you can receive an injection again. 
 
Antacid medicines  
Antacids, to treat indigestion and heartburn, can stop Vocabria tablets being absorbed into your body 
and make it less effective. 
Do not take an antacid during the 2 hours before you take a Vocabria, tablet or for at least 4 hours 
after you take it. Talk to your doctor for further advice on taking acid-lowering (antacid) medicines 
with Vocabria tablets. 
 
If you take more Vocabria than you should 
If you take too many tablets of Vocabria, contact your doctor or pharmacist for advice. If possible, 
show them the Vocabria tablet bottle. 
 
If you forget to take Vocabria 
If you notice within 12 hours of the time you usually take Vocabria, take the missed tablet as soon as 
possible. If you notice after 12 hours, then skip that dose and take the next dose as usual.  
 Do not take a double dose to make up for a forgotten tablet. 



98 

 
If you vomit less than 4 hours after taking Vocabria, take another tablet. If you vomit more than 4 
hours after taking Vocabria you do not need to take another tablet until your next scheduled dose. 
 
Don’t stop taking Vocabria without advice from your doctor 
Take Vocabria for as long as your doctor recommends. Don’t stop unless your doctor advises you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Very common side effects 
These may affect more than 1 in 10 people: 

• headache 
• feeling hot (pyrexia). 
 

Common side effects 
These may affect up to 1 in 10 people: 

• depression 
• anxiety 
• abnormal dreams 
• difficulty in sleeping (insomnia) 
• dizziness 
• feeling sick (nausea)  
• vomiting 
• stomach pain (abdominal pain) 
• wind (flatulence) 
• diarrhoea 
• rash 
• muscle pain (myalgia) 
• lack of energy (fatigue) 
• feeling weak (asthenia) 
• generally feeling unwell (malaise) 
• weight gain. 

 
Uncommon side effects 
These may affect up to 1 in 100 people: 

• feeling drowsy (somnolence) 
• liver damage (signs may include yellowing of the skin and the whites of the eyes, loss of 

appetite, itching, tenderness of the stomach, light-coloured stools or unusually dark urine) 
• changes in liver blood tests (increase in transaminases or increase in bilirubin). 

 
Other side effects that may show up in blood tests 

• an increase in lipases (a substance produced by the pancreas) 
 
Other possible side effects 

People taking Vocabria and rilpivirine therapy for HIV may get other side effects. 
 



99 

Allergic reactions 
Vocabria contains cabotegravir, which is an integrase inhibitor. Other integrase inhibitors can cause a 
serious allergic reaction known as a hypersensitivity reaction, although this has not been seen with 
Vocabria. 
If you get any of the following symptoms: 

• skin rash 
• a high temperature (fever) 
• lack of energy (fatigue) 
• swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
• muscle or joint aches. 

 
 See a doctor straight away. Your doctor may decide to carry out tests to check your liver, 

kidneys or blood, and may tell you to stop taking Vocabria. 
 
Pancreatitis 
 
If you get severe pain in the abdomen (tummy), this may be caused by inflammation of your pancreas 
(pancreatitis). 
 
  Tell your doctor, especially if the pain spreads and gets worse. 
 

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 and/or muscle pain 
• joint pain or swelling 
• 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 and inflammation 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. 
 
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 Vocabria 
 
Keep this medicine out of the sight and reach of children. 

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


100 

 
Do not use this medicine after the expiry date which is stated after EXP on the carton and bottle. The 
expiry date refers to the last day of that month. 
 
This medicine does not require any special temperature 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 protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Vocabria contains 
The active substance is cabotegravir. Each tablet contains 30 mg cabotegravir. 
 
The other ingredients are: 
 
Tablet core 
Lactose Monohydrate 
Microcrystalline Cellulose (E460) 
Hypromellose (E464) 
Sodium Starch Glycolate 
Magnesium Stearate 
 
Tablet coating 
Hypromellose (E464) 
Titanium Dioxide (E171) 
Macrogol (E1521) 
 
What Vocabria looks like and contents of the pack 
Vocabria film-coated tablets are white, oval, film-coated tablets, debossed with ‘SV CTV’ on one side. 
 
The film-coated tablets are provided in bottles closed with child-resistant closures.  
 
Each bottle contains 30 film-coated tablets. 
 
Marketing Authorisation Holder 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H,  
3811 LP Amersfoort  
Netherlands 
 
Manufacturer 
Glaxo Wellcome, S.A.  
Avda. Extremadura, 3 
Aranda De Duero 
Burgos 09400 
Spain 
 
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 
 

mailto:info.lt@gsk.com


101 

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 69 69 
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 

 
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 

mailto:viiv.med.info@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com


102 

 
Italia 
ViiV Healthcare S.r.l  
Tel: + 39 (0)45 7741600 
 

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

 
Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 397000 
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 Limited 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  

  
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 


	ANNEX I 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