Apretude 600 mg/3 ml Suspension

APRETUDE is used to reduce the risk of getting HIV-1 infection in people weighing 35 kg or more. This is called pre-exposure prophylaxis (PrEP). APRETUDE contains the active ingredient cabotegravir, which belongs to a group of anti-retroviral medicines called integrase inhibitors (INIs).

You must not receive APRETUDE injection:

• if you are allergic (hypersensitive) to cabotegravir or to any of the other ingredients of APRETUDE (listed in section 6)
• if you are taking any of these medicines:
  • rifampicin or rifapentine (to treat some bacterial infections such as tuberculosis)
  • phenytoin, phenobarbitone, carbamazepine or oxcarbazepine (also known as anticonvulsants used to treat epilepsy and prevent fits (seizures))
• unless you have had a recent HIV test to confirm you are HIV-negative. APRETUDE can only help reduce your risk of getting HIV before you are infected so, you must get tested to make sure you don’t already have HIV infection before taking APRETUDE.

Conditions you need to look out for:

APRETUDE can cause serious side effects. You must look out for certain symptoms while you are taking APRETUDE and tell your doctor.

Severe skin reactions:

The serious skin reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely in association with APRETUDE. Stop using APRETUDE and seek medical attention immediately if you notice any of the symptoms related to these serious skin reactions. Read the information in section 4 of this Leaflet (Possible side effects).

Allergic reaction:

APRETUDE can cause a serious allergic reaction known as a hypersensitivity reaction. You need to know about important signs and symptoms to look out for while you are receiving APRETUDE. See ‘Allergic Reactions’ in Section 4.

Warnings and precautions:

Take special care with APRETUDE injection:

Just receiving APRETUDE may not stop you getting HIV: You can still get HIV when taking this medicine, although APRETUDE lowers the risk. HIV infection is spread by sexual contact with someone who has the infection or by transfer of infected blood. To reduce your risk of getting HIV:

• Use a condom when you have oral or penetrative sex.
• Don’t risk blood transfer - for example, don’t share needles.

Discuss with your doctor the additional precautions needed to further decrease the risk getting HIV.

While receiving APRETUDE injections to reduce the risk of getting HIV:

• it is important that you attend your planned appointments to receive your APRETUDE injection. Talk to your doctor if you are thinking about stopping injections as this may increase your risk of getting HIV infection. If you do stop or are late receiving your APRETUDE injection, you will need to take other medicines or precautions to reduce your risk of getting HIV and possibly developing viral resistance.
• Get tested for HIV every 2-3 months.
• If you think you were infected with HIV (you may get a flu-like illness), tell your doctor straight away. They may want to do more tests to make sure you are still HIV-negative.

APRETUDE injection is a long-acting medication, so if you stop APRETUDE injections, cabotegravir will remain in your system for up to a year or more after your last injection. It is important that you attend your planned appointments to receive APRETUDE injection and talk to your doctor if you are thinking about stopping PrEP. You may need to take other medicines to reduce the risk of getting HIV infection or use other safe sex precautions if you stop APRETUDE injections.

Liver problems:

Let your doctor know if you have liver problems. Your liver function may need to be closely monitored. (See also ‘Liver problems’ in section 4).

APRETUDE Injections contain mannitol which may have a mild laxative effect.

Other medicines and APRETUDE injection:

Always tell your healthcare provider if you are taking any other medicine. (This includes all complementary and traditional medicines.) Some medicines can affect how APRETUDE works or make it more likely that you will have side effects. APRETUDE can also affect how some other medicines work.

Don't take APRETUDE with these medicines:

• carbamazepine, oxcarbazepine, phenobarbital, or phenytoin (also known as anticonvulsants used to treat epilepsy and prevent fits (seizures)),
• rifampicin or rifapentine (to treat some bacterial infections such as tuberculosis).

Tell your doctor if you are taking any of the medicines in the following list:

• rifabutin (to treat some bacterial infections such as tuberculosis).

Tell your doctor or pharmacist if you are taking any of the above. Your doctor may decide that you need extra check-ups.

Pregnancy and breastfeeding and fertility:

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist, or other healthcare provider for advice before you are given APRETUDE Injections.

If you are planning to have a baby, talk to your doctor in advance, as APRETUDE injection can stay in your system for up to 12 months or longer, after the last injection of APRETUDE. It is not known whether the ingredients of APRETUDE can pass into breast milk and harm your baby. APRETUDE may still pass into breast milk for 12 months after the last injection.

Talk to your doctor immediately, if you are breastfeeding, or thinking about breastfeeding.

Driving and using machines:

APRETUDE can make you dizzy and have other side effects that make you less alert. Don’t drive or use machines unless you are sure you are not affected.

Do not share medicines prescribed for you with any other person. Your doctor will schedule regular appointments according to the dosing schedule he will put you on. Check with your doctor if you are not sure.

You are not expected to administer the injection to yourself. It will be given to you by your doctor or his nurse, in the muscle of your buttock (intramuscular injection). You will be given APRETUDE as a single injection once every two months.

If you will miss an APRETUDE injection:

If you are not able to receive your injection, your doctor may recommend you take APRETUDE tablets instead, until you can receive an injection again. Your doctor will advise you to take one tablet a day until your next APRETUDE injection.

You will need regular blood tests:

For as long as you are using APRETUDE injection, your doctor will arrange regular blood tests to test for HIV infection and to check for side effects. There is more information about these side effects in Section 4 of this leaflet.

When you first start PrEP with APRETUDE, you and your doctor may decide to either:

• start PrEP directly with APRETUDE injection.
• start PrEP with APRETUDE tablets. If you start with APRETUDE tablets, the doctor will advise you to:
  • take one 30 mg APRETUDE tablet once a day, for approximately one month, then receive injections every 2 months.
  • Your first injection should preferably be on the same day as your last tablet or no later than 3 days after. This first month of tablets is called the oral lead-in period. It allows your doctor to assess whether it’s appropriate to proceed with injections.

Injection Schedule for every 2-month dosing:

Which medicine When

First and second injections one month apart

Third injection onwards, every two months

Apretude 600 mg / 3 mL 600 mg / 3 mL

If you are given more APRETUDE injection than you should:

A doctor or nurse will give this medicine to you, so it is unlikely that you will be given too much. If you are worried, tell the doctor or nurse.

You may need regular blood tests:

While you’re taking APRETUDE, your doctor may arrange regular blood tests to check for side effects. There is more information about these side effects in Section 4 of this leaflet.

Keep in touch with your doctor and attend your planned appointments to receive APRETUDE injections. Don’t stop without your doctor’s advice. If you miss an APRETUDE injection: Contact your doctor immediately to make a new appointment. It is important that you keep your regular planned appointments to receive your APRETUDE injection to reduce the risk of getting HIV. Talk to your doctor if you are thinking about stopping APRETUDE. Don’t stop receiving APRETUDE injections without advice from your doctor. Use APRETUDE for as long as your doctor recommends. Don’t stop unless your doctor advises you to. If you miss an appointment to receive your injection, contact your doctor right away to make a new appointment.

APRETUDE can have side effects. Not all side effects reported for APRETUDE are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking APRETUDE, please consult your healthcare provider for advice.

Serious skin reactions:

Stop using Apretude and seek medical attention immediately if you notice any of the following symptoms:

• reddish non-elevated, target-like or circular patches on the trunk, often with central blisters, skin peeling, ulcers of the mouth, throat, nose, genitals, and eyes. These serious skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Allergic Reactions:

These are uncommon in people taking APRETUDE. Signs include:

• skin rash
• a high temperature (fever)
• lack of energy (fatigue)
• raised and itchy rash (hives)
• swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing
• muscle or joint aches.

Contact your doctor as soon as possible. Your doctor may decide to carry out tests on your liver, kidneys or blood, and may tell you to stop APRETUDE injections.

The following side effects can also occur. Some side effects may only be seen in your blood tests and may not appear immediately after you start using APRETUDE. If you get any of these effects, and if they are severe, your doctor may advise you to stop using APRETUDE.

Frequent side effects:

• headache
• diarrhoea
• injection site reactions, these were generally mild to moderate and became less frequent over time. Symptoms include:

- Frequent: pain and tenderness, a hardened mass or lump, redness, itching, swelling, warmth, numbness, or bruising (which may include discolouration or a collection of blood under the skin)

- Less frequent: an abscess (collection of pus)

• changes in liver blood tests (increase in transaminases)
• feeling hot (pyrexia)
• depression
• abnormal dreams
• difficulty in sleeping (insomnia)
• dizziness
• feeling sick (nausea)
• being sick (vomiting)
• stomach pain (abdominal pain)
• wind (flatulence)
• rash
• muscle pain (myalgia)
• lack of energy (fatigue)
• generally feeling unwell (malaise).

Less frequent side effects:

• weight gain
• feeling lightheaded, during or following an injection. This may lead to fainting
• liver damage (signs may include yellowing of the skin and the whites of the eyes, loss of appetite, itching, tenderness of the stomach, light-coloured stools, or unusually dark urine), hepatotoxicity
• suicidal thoughts, suicidal events (mainly in patients who have had depression or mental health conditions before).

Tell your doctor or pharmacist if any of the side effects listed becomes severe or troublesome, or if you notice any side effects not listed in this leaflet.

Reporting of side effects: If you get side effects, talk to your doctor or pharmacist or nurse. You can also report side effects to SAHPRA via the Med Safety App (Medsafety X SAHPRA) and eReporting platform (who-umc-org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of APRETUDE injections.

Store all medicines out of reach of children.

Unopened packs: Store at or below 30 ºC. Do not freeze.

Open packs: Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible but may be stored for up to 2 hours at room temperature. If 2 hours are exceeded, the medication, syringe and needle must be discarded.

Do not use after the expiry date on the label or carton. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g., toilets).