Rekambys

Package leaflet: Information for the user

REKAMBYS 600 mg prolonged-release injectable suspension

rilpivirine

This medicinal product is under additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

What is in this leaflet

1. What REKAMBYS is and what it is used for
2. What you need to know before using REKAMBYS
3. How REKAMBYS is administered
4. Possible side effects
5. How to store REKAMBYS
6. Contents of the pack and other information

1. What REKAMBYS is and what it is used for

REKAMBYS contains the active substance rilpivirine. It belongs to a group of medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are used to treat human immunodeficiency virus type 1 (HIV-1) infection.
REKAMBYS works in combination with other anti-HIV medicines to block the virus's ability to make copies of itself. REKAMBYS injections do not cure HIV infection, but help reduce the amount of HIV in the body and keep it at a low level. This helps prevent damage to the immune system and the development of AIDS-related infections and diseases.
REKAMBYS is always administered together with another injectable anti-HIV medicine called cabotegravir. They are used together in adults and adolescents (at least 12 years of age and weighing at least 35 kg) who already have their HIV-1 infection under control.

2. What you need to know before using REKAMBYS

Do not use REKAMBYS if you are allergic to rilpivirine or any of the other ingredients of this
medicinal product (listed in section 6).
Do not use REKAMBYS if you are taking any of the following medicines, because they may
affect the activity of REKAMBYS or of the other medicine:

• carbamazepine, oxcarbazepine, phenobarbital, phenytoin (medicines used to treat epilepsy and prevent epileptic seizures)
• rifabutin, rifampicin, rifapentine (medicines used to treat certain bacterial infections, such as tuberculosis)
• dexamethasone (a corticosteroid used for various conditions, such as inflammation and allergic reactions) when taken orally or by injection
• products containing St. John’s wort (Hypericum perforatum, a herbal remedy for depression).

If you are taking any of these medicines, consult your doctor for advice on alternative treatments.
Warnings and precautions
Talk to your doctor or pharmacist before using REKAMBYS.
Inform your doctor about your medical condition
Review the following points and inform your doctor if any of these apply to you.

• Inform your doctor if you have or have had liver problems, including hepatitis B or C, or kidney problems. Your doctor may check how well your liver or kidneys are working to determine whether you can use REKAMBYS. See “Uncommon side effects” in section 4 of this leaflet for signs of liver damage.
• Inform your doctor immediately if you notice any symptoms of infection (for example, fever, chills, sweating). In some HIV patients, inflammation caused by previous infections may occur soon after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that were previously present but did not cause obvious symptoms.
• Immediately inform your doctor if you notice any symptoms such as muscle weakness, weakness starting in the hands and feet and progressing toward the trunk, palpitations, tremor, or hyperactivity. This is because autoimmune disorders (conditions in which the immune system mistakenly attacks healthy body tissues) may occur even after starting treatment for HIV infection. Autoimmune disorders may appear several months after treatment initiation.
• Inform your doctor if you are taking medicines that, according to information you have received, may cause a potentially life-threatening irregular heartbeat (torsade de pointes).

Reactions to injections
In some individuals, post-injection reaction symptoms occurred within minutes after the rilpivirine injection. Most symptoms resolved within a few minutes after the injection.
Symptoms of post-injection reactions may include: difficulty breathing, stomach cramps, rash, sweating, numbness of the mouth, feeling of anxiety, sensation of warmth, dizziness or feeling faint, changes in blood pressure, and pain (e.g., in the back and chest). Inform the healthcare provider if you experience any of these symptoms after receiving the injections.
It is important to keep your appointments
It is important to attend all scheduled appointments for REKAMBYS administration to monitor your HIV infection and prevent worsening of the disease. Do not miss any visits, as this is very important for treatment success. If you are unable to attend a scheduled visit, inform your doctor as soon as possible. Talk to your doctor if you are considering stopping treatment. If you miss the appointment on the day scheduled for the REKAMBYS injection or if you discontinue REKAMBYS therapy, you will need to take other medicines to treat HIV infection and to reduce the risk of the virus becoming resistant when drug levels in your body become too low to control HIV infection.
Children
REKAMBYS is not intended for use in children under 12 years of age or in adolescents weighing less than 35 kg, as it has not been studied in these patients.
Other medicines and REKAMBYS
Inform your healthcare provider if you are taking, have recently taken, or might take any other medicines. Some medicines may affect REKAMBYS blood levels if taken during REKAMBYS treatment, or REKAMBYS may affect how other medicines work.
REKAMBYS must not be administered with certain medicines (see "Do not use
REKAMBYS" in section 2).
The effects of REKAMBYS or other medicines may change if you use REKAMBYS together with any of the following medicines:

• clarithromycin, erythromycin (antibiotics)
• methadone (used to treat narcotic dependence and withdrawal)

If you are taking any of these medicines, consult your doctor for advice on alternative treatments.
Pregnancy and breastfeeding
If you are pregnant or planning to become pregnant, inform your doctor immediately.
Your doctor will evaluate the benefits and risks of using REKAMBYS during pregnancy for you and your baby. If you are planning a pregnancy, discuss this with your doctor beforehand, because rilpivirine may remain in the body for up to 4 years after the last REKAMBYS injection.
Breastfeeding is not recommended for HIV-positive women because HIV infection can be transmitted to the infant through breast milk.
If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Some patients may experience fatigue, dizziness, or drowsiness during treatment with REKAMBYS. Do not drive or operate machinery if you experience any of these side effects.
REKAMBYS contains sodium
This medicinal product contains less than 1 mmol of sodium (23 mg) per injection, i.e., essentially “sodium-free”.

3. How REKAMBYS is administered

REKAMBYS will be administered to you by a doctor or nurse as an injection into the muscle of the buttock ( intramuscular or i.m. injection ).
The injection will be given once every month or once every two months, together with another injectable medicine called cabotegravir. Your doctor will explain to you how often the medicine will be administered.
When starting treatment with REKAMBYS, you and your doctor may decide to begin with a daily oral regimen of one 25 mg tablet of rilpivirine taken with a meal and one 30 mg tablet of cabotegravir for one month before the first injection of REKAMBYS. This period is called the induction period – taking these tablets before receiving the REKAMBYS and cabotegravir injections allows your doctor to assess how well these medicines are tolerated by you.
Alternatively, you and your doctor may decide to start directly with the REKAMBYS injections.

If you receive REKAMBYS every month, your treatment will be as follows:

| When | Medicine | First injection | From the second injection onwards, every month |
|------|--------------|---------------------|--------------------------------------------------|
| Rilpivirine | Single 900 mg injection | 600 mg by monthly injection |
| Cabotegravir | Single 600 mg injection | 400 mg by monthly injection |

If you receive REKAMBYS every two months, your treatment will be as follows:

| When | Medicine | First and second injection,
one month apart | From the third injection onwards,
every two months |
|------|--------------|----------------------------------|------------------------------------------|
| Rilpivirine | Single 900 mg injection | 900 mg by injection every two months |
| Cabotegravir | Single 600 mg injection | 600 mg by injection every two months |

If you miss an injection of REKAMBYS
It is important to keep your scheduled appointments for receiving the injection. If you miss an appointment, contact your doctor immediately to reschedule.
Talk to your doctor if you think you may not be able to attend a scheduled appointment for your REKAMBYS injection. Your doctor may advise you to take tablets until you are able to receive the REKAMBYS injection again.

If you are given too much REKAMBYS
This is unlikely to occur, as this medicine will be administered by a doctor or nurse. For any concerns, speak to your doctor or nurse.

Do not stop using REKAMBYS without first consulting your doctor.
REKAMBYS should be used for the entire duration recommended by your doctor. Do not discontinue this treatment unless instructed by your doctor.
Low levels of rilpivirine (the active substance in REKAMBYS) may remain in the body for up to 4 years after stopping treatment. However, after your last REKAMBYS injection, the low levels of rilpivirine that remain will not be sufficient to act against the virus, which may then become resistant. To control HIV-1 infection and prevent the virus from developing resistance, you must start a different anti-HIV treatment regimen before your next scheduled REKAMBYS injection.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following is a list of side effects that have been reported when REKAMBYS is used together with cabotegravir injection.

Very common side effects (may affect at least 1 in 10 people)

• headache
• injection site reactions: these reactions are generally mild to moderate and have become less frequent over time. Symptoms may include: pain and discomfort, formation of a lump or hardened mass
• feeling hot/fever (pyrexia), which may occur within one week after injections

Common side effects (may affect less than 1 in 10 people)

• depression
• anxiety
• abnormal dreams
• difficulty sleeping (insomnia)
• dizziness
• nausea
• vomiting
• stomach ache (abdominal pain)
• abdominal gas (flatulence)
• diarrhoea
• rash
• muscle pain (myalgia)
• tiredness (fatigue)
• feeling of weakness (asthenia)
• feeling generally unwell
• weight gain
• injection site reactions – generally mild to moderate and diminish over time. Symptoms may include: redness, itching, swelling, feeling of warmth or bruising (which may include skin discoloration or accumulation of blood under the skin)

Uncommon side effects (may affect less than 1 in 100 people)

• drowsiness
• feeling faint or dizzy, during or after an injection, possibly leading to fainting
• liver damage (signs may include yellowing of the skin and whites of the eyes, loss of appetite, itching, abdominal tenderness, pale stools or unusually dark urine)
• abnormal liver blood tests (increase in transaminases)
• increased bilirubin (a substance produced by the liver) in the blood
• injection site reactions – generally mild to moderate and diminish over time. Symptoms may include: numbness, minor bleeding, abscess (collection of pus), or cellulitis (feeling of warmth, swelling or redness of the skin)

Other side effects

• severe abdominal pain caused by inflammation of the pancreas (pancreatitis)

The following side effects, which may occur with rilpivirine tablets, may also occur with REKAMBYS injections.

Very common side effects (may affect at least 1 in 10 people)

• increased cholesterol and/or pancreatic amylase in the blood

Common side effects (may affect less than 1 in 10 people)

• loss of appetite
• sleep disorders
• depressed mood
• stomach discomfort
• dry mouth
• low white blood cell count and/or platelet count, decreased haemoglobin levels in the blood, increased triglycerides and/or lipase in the blood

Uncommon side effects (may affect less than 1 in 100 people)

• signs or symptoms of inflammation or infection, for example fever, chills, sweating (immune reconstitution syndrome – see section 2 for further details)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store REKAMBYS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after “Exp.”. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What REKAMBYS contains

• The active substance is rilpivirine. Each 2 mL vial contains 600 mg of rilpivirine.
• The excipients are poloxamer 338, citric acid monohydrate (E330), glucose monohydrate, monosodium dihydrogen phosphate monohydrate, sodium hydroxide (E524) for pH adjustment and maintenance of isotonicity, and water for injections.

Description of the appearance of REKAMBYS and contents of the pack
Prolonged-release injectable suspension. REKAMBYS is contained in a glass vial. The pack also contains 1 syringe, 1 vial adapter, and 1 injection needle.

Marketing Authorization Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien
ViiV Healthcare srl/bv
Tél/Tel: + 32 (0) 10 85 65 00
[email protected]

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
[email protected]

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227
[email protected]

Danmark
Janssen-Cilag A/S
Tlf.: +45 4594 8282
[email protected]

Deutschland
ViiV Healthcare GmbH
Tel.: + 49 (0)89 203 0038-10
[email protected]

Eesti
UAB “JOHNSON & JOHNSON” Eesti filiaal
Tel: +372 617 7410
[email protected]

Ελλάδα
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

España
Laboratorios ViiV Healthcare, S.L.
Tel: + 34 900 923 501
[email protected]

France
ViiV Healthcare SAS
Tél.: + 33 (0)1 39 17 69 69
[email protected]

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
[email protected]

Ireland
Janssen Sciences Ireland UC
Tel: 1 800 709 122
[email protected]

Ísland
Janssen-Cilag AB
c/o Vistor hf.
Sími: +354 535 7000
[email protected]

Italia
ViiV Healthcare S.r.l
Tel: +39 045 7741600

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Latvija
UAB “JOHNSON & JOHNSON” filiāle Latvijā
Tel: +371 678 93561
[email protected]

Lietuva
UAB “JOHNSON & JOHNSON”
Tel: +370 5 278 68 88
[email protected]

Luxembourg/Luxemburg
ViiV Healthcare srl/bv Belgique/Belgien
Tél/Tel: + 32 (0) 10 85 65 00
[email protected]

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
[email protected]

Malta
AM MANGION LTD
Tel: +356 2397 6000

Nederland
ViiV Healthcare BV
Tel: + 31 (0) 33 2081199

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
[email protected]

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00

Portugal
VIIVHIV HEALTHCARE, UNIPESSOAL, LDA
Tel: + 351 21 094 08 01
[email protected]

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
[email protected]

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
[email protected]

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
[email protected]

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:

Instructions for Use of REKAMBYS 2 mL Injection:

General Description
A complete dose requires two injections:
2 mL of cabotegravir and 2 mL of rilpivirine.
Cabotegravir and rilpivirine are suspensions that do not require further dilution or
reconstitution. The preparation procedure is identical for both medications. Follow carefully
these instructions when preparing the injectable suspension to avoid leakage of liquid.
Cabotegravir and rilpivirine are for intramuscular use only. Both injections must
be administered at separate injection sites in the gluteal muscles.
Note: The ventrogluteal site is recommended. The order of administration is

not important.
Storage Information

• Store in a refrigerator at a temperature between 2 °C and 8 °C. Do not freeze.

Package Contents

• 1 vial of rilpivirine
• 1 vial adapter
• 1 syringe
• 1 syringe needle (23 G, 1½ inches)

Consider the patient's body habitus and, based on clinical judgment, select a needle of appropriate length for
injection.

Rilpivirine Vial Vial Adapter
Vial Cap
(rubber stopper under
the cap)
Syringe Injection Needle
Plunger
Needle Shield
Needle Cap
Additional Supplies Required

• Non-sterile gloves
• 2 alcohol swabs
• 2 gauze pads
• A suitable sharps container

1 package of 2 mL cabotegravir
Ensure the closed 2 mL cabotegravir package is readily available before starting.
Preparation

1. Inspect the vial

• Check that the expiration date has not been exceeded

Check the
expiration date.

expiration date and

• Inspect the vial immediately. If the medicine shows visible foreign particulate matter, do not use the medicine.

Do not use if the expiration date has been exceeded.

2. Wait for 15 minutes

• Wait at least 15 minutes before

proceeding with the injection, to allow the

Wait
medicinal product to reach room
15 minutes
temperature.

3. Shake vigorously

Holding the vial firmly, shake it
vigorously for 10 seconds, as illustrated
10
in the figure.
sec.

4. Inspect the suspension

Invert the bottle and check the
resuspension, which should have a
uniform appearance. If the suspension is not uniform,
shake the bottle again.

• It is normal to see small air bubbles.

Note: The order of preparation of the bottles

is not important.

5. Remove the vial cap

Remove the cap from the vial.

• Wipe the rubber stopper with an alcohol swab.

Avoid any contact with the rubber
stopper after disinfection.

6. Open the vial adapter container

Peel off the protective paper from the
vial adapter container.
Note: do not remove the adapter from its
container at this stage. The adapter
will not fall out if the container is inverted.

7. Apply the adapter to the vial

Place the vial on a flat surface.

• Press the adapter onto the vial, as shown in the figure.
• The adapter should snap into place with an audible "click".

click

8. Lift the container

Lift the vial adapter container,
as shown.

9. Prepare the syringe

Remove the syringe from its packaging.

• Draw 1 mL of air into the syringe. This step will facilitate drawing up the liquid in the next step.

10. Attach the syringe

Hold the vial and its adapter firmly, as shown in the figure.

• Screw the syringe securely onto the vial adapter.

11. Press the plunger

Press the plunger all the way down,
introducing the air into the vial.

12. Slowly draw up the dose

Invert the syringe and vial, then
slowly draw up as much liquid as possible
into the syringe. The amount of liquid in the
vial may be more than the prescribed dose.
Note: keep the syringe in a vertical position

to prevent leakage of the liquid.

13. Unscrew the syringe

Firmly hold the syringe plunger in place as shown to prevent leakage of liquid. It is normal to feel some resistance.

• Remove the syringe by unscrewing it from the vial adapter, holding the adapter as illustrated in the figure.

Note: check that the suspension has a uniform appearance and is white and milky.

14. Attach the needle

Partially open the needle packaging
to expose only the base of the needle.

• Holding the syringe vertically, firmly insert it into the needle with a twisting motion.
• Remove the needle cover.

Injection

15. Prepare the injection site

Injections must be administered at the

gluteal site. Choose one of the following areas for the injection:

• Ventrogluteal (recommended site)
• Dorsogluteal (upper outer quadrant)

Note: Administer the injection exclusively via the intramuscular route at the gluteal site.
Do not inject intravenously.
Dorsogluteal

Ventrogluteal

16. Remove the needle cap

Fold the needle cover outward,
away from the needle.

• Remove the cap from the injection needle.

17. Remove excess liquid

• Hold the syringe with the needle pointing upwards.

Push the plunger up to the 2 mL mark to remove
excess liquid and any air bubbles.

Note: disinfect the injection site with a
2 ml
alcohol swab. Allow the skin to dry in the air before proceeding.

18. Stretch the skin

Use the z-track injection technique to
minimize the risk of leakage of
medication from the injection site.

2.5 cm

• Firmly stretch the skin covering the injection site and displace it approximately 2.5 cm.
• Keep the skin in this position while administering the injection.

19. Insert the needle

Insert the needle fully or deep enough to
reach the muscle.

20. Inject the dose

While continuing to keep the skin taut,
slowly push the plunger all the way in.

• Make sure the syringe is empty.
• Remove the needle and immediately release the skin.

21. Examine the injection site

• Apply pressure to the injection site with a gauze pad.
• If bleeding occurs, a plaster may be applied.

Do not massage the area.

22. Avoid the risk of needlestick injury

Fold the needle cap over the needle.

• Gently press the needle cap against a hard surface to lock it in place.
• The needle cap locks into place with a "click".

click
After the injection

23. Safe Disposal

Dispose of used needles, syringes, vials, and adapters
according to local health and safety regulations.
Repeat the procedure for the second medicine

If cabotegravir has not yet been injected,
follow the specific instructions for use provided
with the medicine for its preparation and injection.
Repeat all
steps for the
second
medicine
Frequently Asked Questions

1. How long can the medicine be kept outside the refrigerator?

The best practice is to inject the medicine as soon as it reaches room temperature.
However, the vial may remain in its carton at room temperature (maximum 25 °C) for up to 6 hours.
Do not return it to the refrigerator. If not used within 6 hours, the vial must be discarded.

2. How long can the medicine remain in the syringe?

The best practice is to inject the drug (at room temperature) as soon as possible after drawing it up
from the vial. However, the drug may remain in the syringe for up to 2 hours before administering
the injection.
If this 2-hour period is exceeded, the drug, syringe, and needle must be discarded.

3. Why is it necessary to inject air into the vial?

Introducing 1 mL of air into the vial facilitates the subsequent withdrawal of the dose into the syringe.
Without air, part of the liquid could inadvertently flow back into the vial, leaving less liquid in the syringe than required.

4. Is the order of administration of the two drugs important?

No, the order is not important.

5. Can anything be done to warm the vial to room temperature more quickly? The best thing to do is to allow the vial to reach room temperature spontaneously. To speed up the warming process, you may use the warmth of your hands, but make sure that the temperature of the vial does not exceed 25 °C. Do not use any other method of heating.

6. Why is the ventrogluteal site recommended for administration?

The ventrogluteal approach, into the gluteus medius muscle, is recommended because this area is located far from major nerves and blood vessels. The dorsogluteal approach, into the gluteus maximus muscle, is acceptable if preferred by the healthcare provider. The injection must not be administered at any other site.

Package leaflet: information for the user

REKAMBYS 900 mg prolonged-release injectable suspension

rilpivirine

This medicinal product is subject to additional monitoring. This will allow for rapid identification of
new safety information. You can help by reporting any side effects you experience while taking
this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine, as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What REKAMBYS is and what it is used for
2. What you need to know before using REKAMBYS
3. How REKAMBYS is administered
4. Possible side effects
5. How to store REKAMBYS
6. Contents of the pack and other information

1. What REKAMBYS is and what it is used for

REKAMBYS contains the active substance rilpivirine. It belongs to a group of medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.
REKAMBYS works in combination with other anti-HIV drugs to block the virus's ability to make copies of itself. REKAMBYS injections do not cure HIV infection, but help reduce the amount of HIV in the body and keep it at a low level. This helps prevent damage to the immune system and the development of AIDS-related infections and diseases.
REKAMBYS is always administered together with another injectable anti-HIV medicine called cabotegravir. They are used together in adults and adolescents (at least 12 years of age and weighing at least 35 kg) who have HIV-1 infection that is already under control.

2. What you need to know before using REKAMBYS

Do not use REKAMBYS if you are allergic to rilpivirine or to any of the other ingredients of this
medicinal product (listed in section 6).
Do not use REKAMBYS if you are taking any of the following medicines, because they may
affect the activity of REKAMBYS or of the other medicine:

• carbamazepine, oxcarbazepine, phenobarbital, phenytoin (medicines used to treat epilepsy and prevent epileptic seizures)
• rifabutin, rifampicin, rifapentine (medicines used to treat certain bacterial infections, such as tuberculosis)
• dexamethasone (a corticosteroid used for various conditions, such as inflammation and allergic reactions) when taken orally or by injection
• products containing St John's wort ( Hypericum perforatum , a herbal remedy for depression).

If you are taking any of these medicines, consult your doctor for advice on alternative treatments.
Warnings and precautions
Talk to your doctor or pharmacist before using REKAMBYS.
Inform your doctor about your medical condition
Check the following points and inform your doctor if any of these conditions apply to you.

• Inform your doctor if you have or have had liver problems, including hepatitis B or C, or kidney problems. Your doctor may monitor the function of your liver or kidneys to determine whether you can use REKAMBYS. See “Uncommon side effects” in section 4 of this leaflet for signs of liver damage.
• Inform your doctor immediately if you notice any symptoms of infection (for example, fever, chills, sweating). In some patients with HIV, inflammation caused by previous infections may occur soon after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that were previously present but did not cause obvious symptoms.
• Immediately inform your doctor if you experience any symptoms such as muscle weakness, weakness starting in the hands and feet and progressing towards the trunk, palpitations, tremor, or hyperactivity. This is because autoimmune disorders (conditions in which the immune system mistakenly attacks healthy body tissues) may occur even after starting treatment for HIV infection. Autoimmune disorders may occur several months after starting treatment.
• Inform your doctor if you are taking medicines that, according to information you have received, may cause a potentially life-threatening irregular heartbeat (torsade de pointes).

Injection-related reactions
In some individuals, post-injection reaction symptoms occurred within minutes after
administration of rilpivirine. Most symptoms resolved within a few minutes after the injection.
Symptoms of post-injection reactions may include: difficulty breathing, stomach cramps,
rash, sweating, numbness of the mouth, feeling anxious, feeling hot, dizziness or feeling faint,
changes in blood pressure, and pain (e.g. in the back and chest). Inform the healthcare provider if you experience any of these symptoms after receiving the injection.
It is important to keep your appointments
It is important to attend all scheduled appointments for administration of
REKAMBYS, in order to monitor your HIV infection and prevent the disease from worsening. Do not miss any appointments, as this is very important for treatment success. If you are unable to attend a scheduled appointment, inform your doctor as soon as possible. Consult your doctor if you are considering stopping treatment. If you missed your appointment on the day scheduled for the REKAMBYS injection or if you have discontinued REKAMBYS therapy, you will need to take other medicines to treat HIV infection and to reduce the risk of the virus becoming resistant when drug levels in your body become too low to treat HIV infection.
Children
The use of REKAMBYS is not recommended in children under 12 years of age or in adolescents weighing less than 35 kg, as it has not been studied in these patients.
Other medicines and REKAMBYS
Inform your healthcare provider if you are taking, have recently taken, or might take any other medicine. Some medicines may affect REKAMBYS blood levels if taken during treatment with REKAMBYS, or REKAMBYS may affect how other medicines work.
REKAMBYS must not be administered with certain medicines (see "Do not use
REKAMBYS" in section 2).
The effects of REKAMBYS or other medicines may change if you take REKAMBYS together
with any of the following medicines:

• clarithromycin, erythromycin (antibiotics)
• methadone (used to treat narcotic dependence and withdrawal)

If you are taking any of these medicines, consult your doctor for advice on alternative treatments.
Pregnancy and breastfeeding
If you are pregnant or planning to become pregnant, inform your doctor immediately.
Your doctor will consider the benefits and risks to you and your baby of using REKAMBYS during pregnancy. If you are planning a pregnancy, discuss this with your doctor in advance, because rilpivirine may remain in the body for up to 4 years after the last REKAMBYS injection.
Breastfeeding is not recommended for women with HIV because HIV infection can be transmitted to the baby through breast milk.
If you are breastfeeding or considering doing so, discuss this with your doctor as soon as possible.
Driving and using machines
Some patients may experience fatigue, dizziness, or somnolence during treatment with
REKAMBYS. Do not drive or operate machinery if you experience any of these side effects.
REKAMBYS contains sodium
This medicinal product contains less than 1 mmol of sodium (23 mg) per injection, i.e. essentially
“sodium-free”

3. How REKAMBYS is administered

REKAMBYS will be administered to you by a doctor or nurse as an injection into the muscle of the buttock ( intramuscular or i.m. injection ).
The injection will be given once every month or once every two months , together with another injectable medicine called cabotegravir. Your doctor will explain how often the medicine will be administered to you.
When starting treatment with REKAMBYS , you and your doctor may decide to begin with a daily tablet of 25 mg rilpivirine taken with a meal and a 30 mg tablet of cabotegravir for one month before the first REKAMBYS injection. This period is known as the induction period – taking these tablets before receiving the REKAMBYS and cabotegravir injections allows your doctor to assess how well these medicines are suitable for you.
Alternatively, you and your doctor may decide to start directly with the REKAMBYS injections.
If you receive REKAMBYS every month, your treatment will be as follows:
When
Medicine First injection From the second injection onwards, every month
Rilpivirine Single 900 mg injection 600 mg by monthly injection
Cabotegravir Single 600 mg injection 400 mg by monthly injection
If you receive REKAMBYS every two months, your treatment will be as follows:
When
Medicine First and second injection, From the third injection onwards,
one month apart every two months
Rilpivirine Single 900 mg injection 900 mg by injection every two months
Cabotegravir Single 600 mg injection 600 mg by injection every two months
If you miss an injection of REKAMBYS
It is important to keep the scheduled appointments for receiving your injection. If you miss an appointment, contact your doctor immediately to reschedule.
Talk to your doctor if you think you may not be able to attend an appointment for your REKAMBYS injection on the scheduled date. Your doctor may advise you to take tablets until you are able to receive the REKAMBYS injection again.
If you are given too much REKAMBYS
This is unlikely to happen, as this medicine will be administered by a doctor or nurse. For any concerns, speak to your doctor or nurse.
Do not stop using REKAMBYS without first consulting your doctor.
REKAMBYS should be used for the entire period recommended by your doctor. Do not stop this treatment unless instructed by your doctor.
Low levels of rilpivirine (the active substance in REKAMBYS) may remain in the body for up to 4 years after stopping treatment. However, after your last REKAMBYS injection, the low levels of rilpivirine that remain will not be effective enough against the virus, which could then become resistant. To keep HIV-1 infection under control and prevent the virus from developing resistance, you must start a different anti-HIV treatment until the next scheduled REKAMBYS injection.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following is a list of side effects that have been reported when REKAMBYS is used together with cabotegravir injection.

Very common side effects (may affect at least 1 in 10 people)

• headache
• injection site reactions: these reactions are generally mild to moderate and have become less frequent over time. Symptoms may include: pain and discomfort, formation of a nodule or hardened mass
• feeling hot/fever (pyrexia), which may occur within one week after injections.

Common side effects (may affect less than 1 in 10 people)

• depression
• anxiety
• abnormal dreams
• difficulty sleeping (insomnia)
• dizziness
• nausea
• vomiting
• stomach ache (abdominal pain)
• abdominal gas (flatulence)
• diarrhoea
• rash
• muscle pain (myalgia)
• tiredness (fatigue)
• feeling of weakness (asthenia)
• feeling generally unwell
• weight gain
• injection site reactions – generally mild to moderate and diminish over time. Symptoms may include: redness, itching, swelling, feeling of warmth or bruising (which may include skin colour changes or blood accumulation under the skin).

Uncommon side effects (may affect less than 1 in 100 people)

• somnolence
• feeling dizzy, during or after an injection, possibly leading to fainting
• liver damage (signs may include yellowing of the skin and whites of the eyes, loss of appetite, itching, abdominal tenderness, pale stools or unusually dark urine)
• abnormal liver blood test results (increase in transaminases)
• increased bilirubin (a substance produced by the liver) in the blood
• injection site reactions – generally mild to moderate and diminish over time. Symptoms may include: numbness, minor bleeding, abscess (collection of pus) or cellulitis (skin warmth, swelling or redness).

Other side effects

• severe abdominal pain due to inflammation of the pancreas (pancreatitis).

The following side effects, which may occur with rilpivirine tablets, may also occur with REKAMBYS injections.

Very common side effects (may affect at least 1 in 10 people)

• increased cholesterol and/or pancreatic amylase in the blood

Common side effects (may affect less than 1 in 10 people)

• loss of appetite
• sleep disorders
• depressed mood
• stomach discomfort
• dry mouth
• low white blood cell count and/or platelet count, decreased haemoglobin levels in blood, increased triglycerides and/or lipase in blood

Uncommon side effects (may affect less than 1 in 100 people)

• signs or symptoms of inflammation or infection, for example fever, chills, sweating (immune reconstitution syndrome, see section 2 for more details)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store REKAMBYS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after “Exp.”. The expiry
date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What REKAMBYS contains

• The active substance is rilpivirine. Each 3 mL vial contains 900 mg of rilpivirine.
• The excipients are poloxamer 338, citric acid monohydrate (E330), glucose monohydrate, monosodium dihydrogen phosphate monohydrate, sodium hydroxide (E524) for pH adjustment and maintenance of isotonicity, and water for injections.

Description of the appearance of REKAMBYS and contents of the pack
Prolonged-release injectable suspension. REKAMBYS is contained in a glass vial. The pack also contains 1 syringe, 1 vial adapter, and 1 injection needle.

Marketing Authorization Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
ViiV Healthcare srl/bv UAB “JOHNSON & JOHNSON”
Tél/Tel: + 32 (0) 10 85 65 00 Tel: +370 5 278 68 88
[email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД ViiV Healthcare srl/bv
Тел.: +359 2 489 94 00 Belgique/Belgien
[email protected] Tél/Tel: + 32 (0) 10 85 65 00

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf.: +45 4594 8282 Tel: +356 2397 6000
[email protected]

Deutschland Nederland
ViiV Healthcare GmbH ViiV Healthcare BV
Tel.: + 49 (0)89 203 0038-10 Tel: +31 (0) 33 2081199
[email protected]

Eesti Norge
UAB “JOHNSON & JOHNSON” Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Janssen-Cilag Pharma GmbH
Α.Ε.Β.Ε. Tel: +43 1 610 300
Tηλ: +30 210 80 90 000

España Polska
Laboratorios ViiV Healthcare, S.L. Janssen-Cilag Polska Sp. z o.o.
Tel: + 34 900 923 501 Tel.: +48 22 237 60 00
[email protected]

France Portugal
ViiV Healthcare SAS VIIVHIV HEALTHCARE, UNIPESSOAL,
Tél.: + 33 (0)1 39 17 69 69 LDA
[email protected] Tel: +351 21 094 08 01
[email protected]

Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: 1 800 709 122 Tel: +386 1 401 18 00
[email protected] [email protected]

Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]

Italia Suomi/Finland
ViiV Healthcare S.r.l Janssen-Cilag Oy
Tel: +39 045 7741600 Puh/Tel: +358 207 531 300
[email protected]

Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]

Latvija
UAB “JOHNSON & JOHNSON” filiāle Latvijā
Tel: +371 678 93561
[email protected]

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

The following information is intended for healthcare professionals only:

Instructions for use of REKAMBYS 3 mL injection:

General description
A complete dose requires two injections:
3 mL of cabotegravir and 3 mL of rilpivirine.
Cabotegravir and rilpivirine are suspensions that require no further dilution or
reconstitution. The preparation procedure is identical for both medicines. Follow carefully
these instructions when preparing the injectable suspension to avoid leakage of liquid.
Cabotegravir and rilpivirine are for intramuscular use only. Both injections must
be administered at separate injection sites in the gluteal muscles.
Note: the ventrogluteal site is recommended. The order of administration is not

important.
Storage information

• Store in a refrigerator at a temperature between 2 °C and 8 °C. Do not freeze.

Package contents

• 1 vial of rilpivirine
• 1 vial adapter
• 1 syringe
• 1 syringe needle (23 G, 1½ inches) Consider the patient's body habitus and, based on clinical judgment, select an injection needle of appropriate length.

Vial adapter
Rilpivirine vial
Vial cap
(rubber stopper
under the cap)

Syringe

Injection needle

Plunger

Needle shield

Needle cap
Additional required materials

• Non-sterile gloves
• 2 alcohol swabs
• 2 gauze pads
• A suitable sharps container

1 package of cabotegravir 3 mL

Ensure the closed 3 mL cabotegravir package is readily available before starting.
Preparation

1. Inspect the vial

• Check that the expiration date has not been
  exceeded.

Check the expiration date.

expiration date and

• Immediately inspect the vial. If the medicine contains visible foreign particulate matter, do not use the medicine.

Do not use if the expiration date has
been exceeded.

2. Wait for 15 minutes

• Wait at least 15 minutes before proceeding

with the injection, to allow the medicine to
reach room temperature.

Wait 15 minutes

3. Shake vigorously

Holding the vial firmly, shake it
vigorously for 10 seconds, as illustrated
10
in the figure.
sec

4. Inspect the suspension

Invert the bottle and check the
resuspension, which should have a
uniform appearance. If the suspension is not uniform,
shake the bottle again.

• It is normal to see small air bubbles.

Note: The order of preparing the bottles
is not important.

5. Remove the vial cap

Remove the cap from the vial.

• Wipe the rubber stopper with an alcohol swab.

Avoid any contact with the rubber stopper after disinfection.

6. Open the vial adapter container

Peel off the protective paper from the
vial adapter container.

Note: do not remove the adapter from its
container for the next step. The adapter
does not fall out if the container is inverted.

7. Attach the adapter to the vial

Place the vial on a flat surface.

• Press the adapter onto the vial as shown in the figure.
• The adapter should snap into place with an audible click ("click").

click

8. Lift the container

Lift the vial adapter container, as shown.

9. Prepare the syringe

Remove the syringe from its packaging.

• Draw 1 mL of air into the syringe. This will make it easier to withdraw the liquid in the next step.

10. Attach the syringe

Hold the vial and its adapter firmly, as shown in the figure.

• Screw the syringe securely onto the vial adapter.

11. Press the plunger

Press the plunger completely down,
introducing the air into the vial.

12. Slowly draw up the dose

Turn the syringe and vial upside down, then
slowly draw up as much liquid as possible
into the syringe. The liquid in the
vial may exceed the prescribed dose.

Note: keep the syringe in an upright position
to prevent leakage of liquid.

13. Unscrew the syringe

Firmly hold the syringe plunger in place as shown to prevent leakage of liquid. It is normal to feel some resistance.

• Remove the syringe by unscrewing it from the vial adapter, holding the adapter as illustrated in the figure.

Note: check that the suspension has a uniform appearance and a white, milky color.

14. Attach the needle

Partially open the needle packaging
to expose only the base of the needle.

• Holding the syringe vertically, firmly insert it into the needle with a twisting motion.
• Remove the needle cover.

Injection

15. Prepare the injection site

Injections must be administered into the

gluteal area. Choose one of the following sites
for the injection:

• Ventrogluteal (recommended site)
• Dorso gluteal (upper outer quadrant)

Note: Administer the injection only
intramuscularly into the gluteal site.
Do not inject intravenously.
Ventrogluteal Dorso gluteal

16. Remove the cap

Fold the needle cover outward,
away from the needle.

• Remove the injection needle cap.

17. Remove excess liquid

• Hold the syringe with the needle pointing upwards.

Push the plunger until the 3 mL mark to remove excess liquid and any air bubbles.

Note: disinfect the injection site with an alcohol-soaked swab. Allow

3 mL
the skin to dry in air before proceeding.

18. Stretch the skin

Use the Z-track injection technique to
minimize the risk of leakage of
medication from the injection site.
2.5 cm

• Firmly stretch the skin covering the injection site, displacing it approximately 2.5 cm.
• Keep the skin in this position while administering the injection.

19. Insert the needle

Insert the needle fully or deep enough
to reach the muscle.

20. Inject the dose

While continuing to keep the skin taut,
slowly press the plunger all the way down.

• Make sure the syringe is empty.
• Remove the needle and immediately release the skin.

21. Examine the injection site

• Apply pressure to the injection site with a gauze pad.
• If bleeding occurs, a plaster may be applied.

Do not massage the area.

22. Avoid needlestick injury risks

Fold the needle cover over the needle.

• Apply slight pressure on the needle cover, pushing it against a hard surface to lock it in place.
• The needle cover locks into position with a "click".

click
After injection

23. Safe Disposal

Dispose of used needles, syringes, vials, and adapters
according to local health and safety regulations.
Repeat the procedure for the second medicine

If cabotegravir has not yet been injected,
follow the specific instructions for use provided
for the preparation and injection of that medicine.
Repeat all
steps for the
second
medicine
Questions and Answers

1. How long can the medicine be kept outside the refrigerator?

The best practice is to inject the medicine as soon as it has reached room temperature. However, the vial can remain in its carton at room temperature (maximum 25 °C) for up to 6 hours. Do not return it to the refrigerator. If not used within 6 hours, the vial must be discarded.

2. How long can the medicine be left in the syringe?

The best practice is to inject the drug (at room temperature) as soon as possible after drawing it up from the vial. However, the medicine may remain in the syringe for up to 2 hours before administering the injection.
If this 2-hour period is exceeded, the medicine, syringe, and needle must be discarded.

3. Why is it necessary to inject air into the vial?

Introducing 1 mL of air into the vial facilitates the subsequent withdrawal of the dose into the syringe.
Without air, part of the liquid might unintentionally flow back into the vial, leaving less than the required amount of liquid in the syringe.

4. Is the order of administration of the two drugs important?

No, the order is not important.

5. Is there anything that can be done to warm the vial to room temperature more quickly? The best approach is to allow the vial to reach room temperature spontaneously. To speed up the warming process, you may use the warmth of your hands, making sure, however, that the temperature of the vial does not exceed 25 °C.

Do not use any other method of heating.

6. Why is the ventrogluteal site recommended for administration?

The ventrogluteal approach, into the gluteus medius muscle, is recommended because this site is located far from major nerves and blood vessels. The dorsogluteal approach, into the gluteus maximus muscle, is acceptable if preferred by the healthcare provider. The injection must not be administered at any other site.