Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands
Apretude is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in high-risk adults and adolescents, weighing at least 35 kg (see sections 4.2, 4.4 and 5.1).
Apretude should be prescribed by a healthcare professional experienced in the management of HIV PrEP.
Each injection should be administered by a healthcare professional.
Individuals must be tested for HIV-1 prior to initiating cabotegravir and at each subsequent injection of cabotegravir (see section 4.3). A combined antigen/antibody test as well as an HIV-RNA-based test should both be negative. Prescribers are advised to perform both tests, even if the result of the HIVRNA-based test will become available after cabotegravir injection. If a combined testing strategy including both tests is not available, testing should follow local guidelines.
Prior to starting Apretude, individuals should be carefully selected to agree to the required dosing schedule and counselled about the importance of adherence to scheduled dosing visits to help reduce the risk of acquiring HIV-1 infection.
The healthcare provider and individual may decide to use cabotegravir tablets as an oral lead-in prior to the initiation of Apretude injection to assess tolerability or may proceed directly to Apretude injections (see Table 1 and Table 2 for dosing recommendations).
Refer to the oral Apretude tablet SmPC for oral lead-in information.
The recommended initial dose is a single 600 mg intramuscular injection. If oral lead-in has been used, the first injection should be planned for the last day of oral lead-in or within 3 days thereafter.
One month later, a second 600 mg intramuscular injection should be administered. Individuals may be given the second 600 mg initiation injection up to 7 days before or after the scheduled dosing date.
After the second initiation injection, the recommended continuation injection dose in adults is a single 600 mg intramuscular injection administered every 2 months. Individuals may be given injections up to 7 days before or after the date of the scheduled injection date.
Table 1. Recommended intramuscular dosing schedule:
| Initiation injections (one month apart) | Continuation injections (two months apart) | |
| Medicinal product | Direct to injection: months 1 and 2 or Following oral lead-in: months 2 and 3 | Two months after final initiation injection and every 2 months onwards |
| Cabotegravir | 600 mg | 600 mg |
Individuals who miss a scheduled injection visit should be reassessed to ensure resumption of PrEP remains appropriate.
If a delay of more than 7 days from a scheduled injection date cannot be avoided it will be a missed dose, therefore, cabotegravir 30 mg tablets may be used once daily, for a duration of up to two months, to replace one scheduled injection visit. The first dose of oral therapy should be taken approximately two months (+/- 7 days) after the last injection of cabotegravir. For oral PrEP durations greater than two months, an alternative PrEP regimen is recommended.
Injection dosing should be resumed on the day oral dosing completes or within 3 days, thereafter, as recommended in Table 2.
Table 2. Injection dosing recommendations after missed injections or following oral PrEP to replace an injection:
| Missed Doses | ||
| Time since last injection | Recommendation | |
| If second injection is missed and time since first injection is: | ||
| ≤2 months | Administer one 600 mg injection as soon as possible and continue with the every 2 month injection dosing schedule. | |
| >2 months | Restart the individual on one 600 mg initiation injection, followed by a second 600 mg initiation injection one month later. Then follow the every two month injection dosing schedule. | |
| If 3rd or subsequent injection is missed and time since prior injection is: | ||
| ≤3 months | Administer one 600 mg injection as soon as possible and continue with the every 2 month injection dosing schedule. | |
| >3 months | Restart the individual on one 600 mg initiation injection, followed by a second 600 mg initiation injection one month later. Then follow the every two month injection dosing schedule. | |
No dose adjustment is required in elderly individuals. There are limited data available on the use of cabotegravir in individuals aged 65 years and over (see section 5.2).
No dose adjustment is required in individuals with mild or moderate hepatic impairment (Child-Pugh score A or B). Cabotegravir has not been studied in individuals with severe hepatic impairment (ChildPugh score C, [see section 5.2]). If administered in an individual with severe hepatic impairment, cabotegravir should be used with caution.
No dose adjustment is required in individuals with mild to severe renal impairment (CrCl <30 mL/min and not on dialysis [see section 5.2]). Cabotegravir has not been studied in individuals 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 an individual on renal replacement therapy, cabotegravir should be used with caution.
The safety and efficacy of cabotegravir in children and adolescents weighing less than 35 kg have not been established. No data are available.
For intramuscular use. Injections must be administered to the ventrogluteal (recommended as it is located away from major nerves and blood vessels) or the dorsogluteal sites.
Care should be taken to avoid inadvertent injection into a blood vessel.
Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible, but may remain in the syringe for up to 2 hours. If the medicinal product remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded.
When administering Apretude injection, healthcare professionals should take into consideration the Body Mass Index (BMI) of the individual to ensure that the needle length is sufficient to reach the gluteus muscle.
There is no specific treatment for Apretude overdose. If overdose occurs, the individual 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 Apretude injection should take into consideration the prolonged exposure to the medicinal product following an injection (see section 4.4).
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, the injection should be used as soon as possible, but may be stored for up to 2 hours. If 2 hours are exceeded, the medicinal product, syringe and needle must be discarded. 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: Do not freeze.
Suspension in syringe: Do not store above 25°C (see section 6.3).
Brown 3 mL type I glass vial, with bromobutyl rubber stopper and a grey aluminium overseal with an orange plastic flip-cap.
Pack sizes of 1 vial or 25 vials. Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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.
Full instructions for use and handling of Apretude injection are provided in the package leaflet (see Instructions for Use).
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