VOCABRIA Prolonged-release suspension for injection Ref.[10733] Active ingredients: Cabotegravir

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 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).

The healthcare provider and patient may decide to use cabotegravir tablets as an oral lead-in prior to the initiation of Vocabria injection to assess tolerability to cabotegravir (see Table 1) or may proceed directly to Vocabria injections (see Table 2 for monthly and Table 3 for every 2 month dosing recommendations).

Posology

Adults

Oral lead-in

When used for oral lead-in, 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).

Table 1. Oral Lead-in Dosing Schedule in Adults:

^a see Table 2 for monthly injection dosing schedule and Table 3 for every 2 month dosing schedule.

Monthly dosing

Initiation injection (600 mg corresponding to 3 mL dose):

On the final day of current antiretroviral therapy or 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 2. Recommended monthly intramuscular dosing schedule in adults:

Every 2 Month Dosing

Initiation Injections – one month apart (600 mg):

On the final day of current antiretroviral therapy or oral lead-in therapy, the recommended initial Vocabria injection in adults is a single 600 mg intramuscular injection.

One month later, 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 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 3. Recommended every 2 month intramuscular dosing schedule in adults:

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 Tables 4 and 5 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 4.

Table 4. Vocabria injection dosing recommendations after missed injections or oral therapy for patients on monthly injection dosing:

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 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 5.

Table 5. Vocabria injection dosing recommendations after missed injections or oral therapy for patients on every 2 month injection dosing:

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 (ChildPugh score C, [see section 5.2]). 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 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.

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.

Unopened vial:

3 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.

Unopened vial:

This medicinal product does not require any special storage conditions. Do not freeze.

Suspension in syringe:

For storage conditions after first opening of the product, see section 6.3.

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]).

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).