VOCABRIA

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.

4). The healthcare provider and patient may decide to use cabotegravir tablets as an oral lead-in prior to the initiation of cabotegravir injection to assess tolerability to cabotegravir (see Table 1) or may proceed directly to cabotegravir injections (see cabotegravir injection SmPC).

4). One Vocabria 30 mg tablet should be taken with one rilpivirine 25 mg tablet, once daily. Table 1 Recommended Dosing Schedule 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.

1. 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. 2). 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).

2]). If administered in a patient with severe hepatic impairment, cabotegravir should be used with caution. Paediatric population The safety and efficacy of Vocabria in children aged less than 12 years or adolescents weighing less than 35 kg have not been established.

No data are 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.

Summary of the safety profile The most frequently reported adverse reactions (ARs) were headache and pyrexia6. 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 Immune system disorders Uncommon Hypersensitivity*2 Common Depression Anxiety Abnormal dreams Insomnia Psychiatric disorders Uncommon Suicide attempt2; Suicidal ideation2 (particularly in patients with a pre-existing history of psychiatric illness) Very common Headache Common Dizziness Nervous system disorders Uncommon Somnolence Gastrointestinal disorders Common Nausea Vomiting Abdominal pain3 Flatulence Diarrhoea Hepatobiliary Disorders Uncommon Hepatotoxicity Common Rash4 Uncommon Urticaria*2 Angioedema*2 Skin and subcutaneous tissue disorders Very rare Stevens-Johnson syndrome*5, toxic epidermal necrolysis*5 Musculoskeletal and connective tissue disorders Common Myalgia Very common Pyrexia6 General disorders and administrative site conditions Common Fatigue Asthenia Malaise Common Weight increasedInvestigations 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 This adverse reaction was identified through post-marketing reporting. The frequency category is based on individuals exposed to cabotegravir in randomised clinical studies. 3 Abdominal pain includes the following grouped MedDRA preferred term: upper abdominal pain.

4 Rash includes the following grouped MedDRA preferred terms: rash, rash erythematous, rash generalised, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic. 5 This adverse reaction was identified through post-marketing reporting.

The frequency category is based on individuals exposed to cabotegravir in clinical studies. 6 Pyrexia includes the following grouped MedDRA preferred terms: feeling hot, body temperature increased. 4 ‘Hypersensitivity reactions’. The overall safety profile at Week 96 and Week 124 in the FLAIR study was consistent with that observed at Week 48, with no new safety findings identified.

1). 5 kg in weight; subjects continuing on their current antiretroviral therapy (CAR) gained a median of 1 kg (pooled analysis). 3 kg in the CAR arms. 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. 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.

1). 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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.

Available data suggest that virologic failure occurs more often when these patients are treated according to the every 2 month dosing regimen as compared to the monthly dosing regimen. 1). Hypersensitivity reactions Hypersensitivity reactions have been reported in association with integrase inhibitors including cabotegravir.

These reactions were characterised by rash, constitutional findings and sometimes organ dysfunction, including liver injury. Vocabria and other suspected medicinal products should be discontinued 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. 1). 8). Administration of cabotegravir oral lead-in was used in clinical studies to help identify patients who may be at risk of hepatotoxicity.

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.

5). 5). 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 does 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.

Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption should not take this medicine.

1. 5).