Special Warning : אזהרת שימוש

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. 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. 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 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. (See sections 4.2, section 4.8 and 5.1).

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). 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
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).

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’.

Effects on Driving

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.