Posology : מינונים

4.2    Posology and method of administration

Therapy should be prescribed by a physician experienced in the management of HIV infection. Each injection should be administered by a healthcare professional.

Prior to starting REKAMBYS, the healthcare professional should carefully select 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 associated with missed doses.

Following discontinuation of REKAMBYS in combination with cabotegravir injection, it is essential to adopt an alternative, fully suppressive antiretroviral regimen no later than one month after the last every 1 month injection of REKAMBYS or two months after the last every 2 months injection of REKAMBYS (see section 4.4).

The prescribing information for cabotegravir injection should be consulted for recommended dosing.

Posology
REKAMBYS may be initiated with oral lead-in or without (direct to injection).

The healthcare professional and patient may decide to use rilpivirine tablets as an oral lead-in prior to the initiation of REKAMBYS injections to assess tolerability (see table 1), or proceed directly to REKAMBYS therapy (see Tables 2 and 3, for monthly and every 2 months docing recommendations, respectively).


Oral lead-in
When used for oral lead-in prior to the initiation of REKAMBYS, rilpivirine oral tablets, together with cabotegravir oral tablets,should be taken for approximately 1 month (at least 28 days) to assess tolerability to rilpivirine and cabotegravir. One rilpivirine 25-mg tablet should be taken with a meal with one cabotegravir 30-mg tablet once daily (see Table 1).

Table 1 Oral                   Oral Lead-In
Lead-in Dosing
Schedule in Adults
Drug                           For 1 month (at least 28 days), followed by the Initiation Injectiona Rilpivirine                    25 mg once daily with a meal
Cabotegravir                   30 mg once daily asee   Table 2 for monthly injection dosing schedule and Table 3 for every 2 months injection dosing schedule 

Every 1 month dosing
Initiation injection (900 mg corresponding to 3 mL)
On the final day of current antiretroviral therapy or oral lead-in, the recommended initiation injection dose of rilpivirine in adults is asingle 900 mg intramuscular injection.

Continuation injection (600 mg corresponding to 2 mL)
After the initiation injection, the recommended continuation injection dose of rilpivirine in adults is a single 600 mg monthly intramuscular injection. Patients may be given injections up to 7 days before or after the date of the monthly injection schedule.

Table 2     Recommended monthly intramuscular injection dosing schedule in adult patients Initiation injection             Continuation injections
Direct to injection: month 1
One month after initiation injection or
Medicinal                                               and monthly onwards Product     Following oral lead-in: month 2
Rilpivirine                    900 mg                             600 mg Cabotegravir                   600 mg                             400 mg 
Every 2 months dosing
Initiation Injections –1 month apart (900 mg corresponding to 3 mL) On the final day of current antiretroviral therapy or oral lead-in, the recommended initial rilpivirine injection dose in adults is a single900 mg intramuscular injection.

One month later, a second 900 mg intramuscular injection should be administered. Patientsmay be given the second 900 mg injection up to 7 days before or after the scheduled dosing date.

Continuation Injections – 2 months apart (900 mg corresponding to 3 mL) After the initiation injections, the recommended rilpivirine continuation injection dose in adults is a single 900 mg intramuscular injection administered every 2 months. Patients may be given injections up to 7 days before or after the date of the every 2 months injection schedule.

Table 3     Recommended every 2 months intramuscular injection dosing schedule in adult patients
Initiation injections            Continuation injections
Medicinal     Direct to injection: months 1 and 2
Product                                             Two months after final initiation or injection and every 2 months
Following oral lead-in: months 2 and 3             onwards
Rilpivirine                       900 mg                            900 mg Cabotegravir                      600 mg                            600 mg 

Dosing Recommendations When Switching From Monthly to Every 2 Months Injections Patients switching from a monthly continuation injection schedule to an every 2 months continuation injection schedule should receive a single 900 mg intramuscular injection of REKAMBYS one month after the last 600 mg REKAMBYS continuation injection dose and then 900 mg every 2 months thereafter.

Dosing Recommendations When Switching From Every 2 Months to Monthly Injections Patients switching from an every 2 months continuation injection schedule to a monthly continuation injection schedule should receive a single 600 mg intramuscular injection of REKAMBYS two months after the last 900 mg REKAMBYS continuation injection dose and then 600 mg monthly thereafter.

Missed doses
Patients who miss an injection visit should be clinically reassessed to ensure resumption of therapy is appropriate. See Table 4 and 5 for dosing recommendations after a missed injection.

Missed every 1 month injection (Oral Dosing to Replace Up to 2 Consecutive Monthly Injections) If a patient plans to miss a scheduled injection by more than 7 days, daily oral therapy (one rilpivirine tablet [25 mg] and one cabotegravir tablet [30 mg]) may be used to replace up to 2 consecutive monthly injection visits. The first dose of oral therapy should be taken 1 month (± 7 days) after the last injection doses of REKAMBYS and cabotegravir. Injection dosing should be resumed on the day oral dosing completes, as recommended in Table 4.
In case more than two months need to be covered for, i.e., missing more than two monthly injections, analternative oral regimen should be initiated one month (± 7 days) after the final injection of REKAMBYS.

Table 4     REKAMBYS 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 600 mg injection schedule as soon as possible.
> 2 months:                Re-initiate the patient on the 900 mg dose, and then continue to follow the monthly 600 mg injection schedule.

Missed every 2 months injection (Oral Dosing to Replace 1 Every 2 Months Injection) If a patient plans to miss a scheduled injection visit by more than 7 days, daily oral therapy (one rilpivirine tablet [25 mg] and one cabotegravir tablet [30 mg]) may be used to replace one ‘every 2 months’ injection visit. The first dose of oral therapy should be taken approximately two months
(±7 days) after the last injection doses of REKAMBYS and cabotegravir. Injection dosing should be resumed on the day oral dosing completes, as recommended in Table 5.
In case more than two months need to be covered for, i.e., missing more than one ‘every 2 months’ injection, an alternative oral regimen should be initiated two months (± 7 days) after the final injection of REKAMBYS.

Table 5     REKAMBYS dosing recommendations after missed injections or oral therapy for patients on every 2 months injection dosing
Missed Injection Time since last Recommendation (all injections are 3 mL) Visit               injection
Injection 2         ≤ 2 months      Continue with the 900 mg injection as soon as possible and continue with every 2 months injection schedule.
> 2 months      Re-initiate the patient on the 900 mg dose, followed by a second 900 mg initiation injection one month later. Then follow the every 2 months injection schedule.
Injection 3 or        ≤ 3 months        Continue with the 900 mg injection as soon as possible and later                                   continue with every 2 months injection schedule.
> 3 months        Re-initiate the patient on the 900 mg dose, followed by a second 900 mg initiation injection one month later. Then follow the every 2 months injection schedule.
Special populations

Elderly
There is limited information regarding the use of REKAMBYS in patients > 65 years of age. No dose adjustment of REKAMBYS is required in older patients (see sections 5.1 and 5.2).

Renal impairment
No dose adjustment is required in patients with mild or moderate renal impairment. In patients with severe renal impairment or end stage renal disease, the combination of REKAMBYS with a strong CYP3A inhibitor should only be used if the benefit outweighs the risk. Subjects with estimated creatinine clearance < 50 mL/min/1.73 m2 were not included in the Phase 3 studies. No data are available in subjects receiving dialysis although differences in pharmacokinetics are not expected in this population (see section 5.2).

Hepatic impairment
No dose adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh score A or B), but caution is advised in patients with moderate hepatic impairment. No data are available in patients with severe hepatic impairment (Child-Pugh score C); therefore REKAMBYS is not recommended in these patients (see section 5.2).

Paediatric population
The safety and efficacy of REKAMBYS in children and adolescents aged < 18 years have not been established. No data are available.

Method of administration

For intramuscular use.
Care should be taken to avoid inadvertent injection of REKAMBYS into a blood vessel. The suspension should be injected slowly (see section 4.4).

Prior to administration, the REKAMBYS vial should be brought to room temperature.

REKAMBYS should be administered by a healthcare professional. For instructions on administration, see “Instructions for Use” in the package leaflet. These instructions should be carefully followed when preparing the suspension for injection to avoid leakage.

REKAMBYS should always be co-administered with a cabotegravir injection. REKAMBYS and cabotegravir injections should be administered at separate gluteal injection sites during the same visit.
The order of injections is not important.

When administering REKAMBYS, the healthcare professional 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. The pack contains 1 injection needle (see section 6.5).

The vial should be held firmly and shaken vigorously for a full 10 seconds. The vial should be inverted and the resuspension should be checked. It should look uniform. If the suspension is not uniform, the vial should be shaken again. It is normal to see small air bubbles.

Injections must be administered to the ventrogluteal (recommended) or the dorsogluteal sites.