Prolia ® 60 mg Solution

What PROLIA ® is and how it works
PROLIA ® contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, in order to treat bone loss and osteoporosis. Treatment with PROLIA ® makes bone stronger and less likely to break.

Bone is a living tissue and is renewed all the time. Oestrogen helps keep bones healthy. After the menopause, oestrogen level drops which may cause bones to become thin and fragile. This can eventually lead to a condition called osteoporosis. Osteoporosis can also occur in men due to a number of causes including ageing and/or a low level of the male hormone, testosterone. It can also occur in patients receiving glucocorticoids. Many patients with osteoporosis have no symptoms, but they are still at risk of breaking bones, especially in the spine, hips and wrists. Surgery or medicines that stop the production of oestrogen or testosterone used to treat patients with breast or prostate cancer can also lead to bone loss. The bones become weaker and break more easily.

What PROLIA ® is used for
PROLIA ® is used to treat:

• osteoporosis in women after the menopause (postmenopausal) and men who have an increased risk of fracture (broken bones), reducing the risk of spinal, non-spinal and hip fractures.
• bone loss that results from a reduction in hormone (testosterone) level caused by surgery or treatment with medicines in patients with prostate cancer.
• bone loss that results from long-term treatment with glucocorticoids in patients who have an increased risk of fracture.

Do not use PROLIA ®

• if you have low calcium levels in the blood (hypocalcaemia).
• if you are allergic (hypersensitive) to denosumab or any of the other ingredients of PROLIA ® (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before using PROLIA ®. Whilst being treated with PROLIA ® you may develop a skin infection with symptoms such as a swollen, red area of skin, most commonly in the lower leg, that feels hot and tender (cellulitis), and possibly with symptoms of fever. Please tell your doctor immediately if you develop any of these symptoms.

You should also take calcium and vitamin D supplements while being on treatment with PROLIA ®. Your doctor will discuss this with you.

You may have low levels of calcium in your blood while receiving PROLIA ®. Please tell your doctor immediately if you notice any of the following symptoms: spasms, twitches, or cramps in your muscle, and/or numbness or tingling in your fingers, toes or around your mouth, and/or seizures, confusion, or loss of consciousness. Severe low blood calcium levels leading to hospitalisation and even life-threatening reactions have been reported in rare cases. Before each dose and in patients predisposed to hypocalcaemia within two weeks after initial dose, the calcium levels in your blood will therefore be checked (via blood test).

Tell your doctor if you have or have ever had severe kidney problems, kidney failure or have needed dialysis or are taking medicines called glucocorticoids (such as prednisolone or dexamethasone), which may increase your risk of getting low blood calcium if you do not take calcium supplements.

Problems with your mouth, teeth or jaw
A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported rarely (may affect up to 1 in 1 000 people) in patients receiving PROLIA ® for osteoporosis. The risk of ONJ increases in patients treated for a long time (may affect up to 1 in 200 people if treated for 10 years). ONJ can also occur after stopping treatment. It is important to try to prevent ONJ developing as it may be a painful condition that can be difficult to treat. In order to reduce the risk of developing ONJ, some take the following precautions: Before receiving treatment, tell your doctor or nurse (healthcare professional if you:

• have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction.
• don’t receive routine dental care or have not had a dental check-up for a long time.
• are a smoker (as this may increase the risk of dental problems).
• have previously been treated with a bisphosphonate (used to treat or prevent bone disorders).
• are taking medicines called corticosteroids (such as prednisolone or dexamethasone).
• have cancer.

Your doctor may ask you to undergo a dental examination before you start treatment with PROLIA ®. While being treated, you should maintain good oral hygiene and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with PROLIA ®. Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, or non-healing of sores or discharge, as these could be signs of ONJ.

Unusual thigh bone fractures
Some people have developed unusual fractures in their thigh bone while being treated with PROLIA ®. Contact your doctor if you experience new or unusual pain in your hip, groin, or thigh.

Children and adolescents
PROLIA ® should not be used in children and adolescents under 18 years of age.

Other medicines and PROLIA ®
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. It is especially important that you tell your doctor if you are being treated with another medicine containing denosumab. You should not take PROLIA ® together with another medicine containing denosumab.

Pregnancy and breastfeeding
PROLIA ® has not been tested in pregnant women. It is important to tell your doctor if you are pregnant; think you may be pregnant; or plan to get pregnant. PROLIA ® is not recommended for use if you are pregnant. Women of child-bearing potential should use effective methods of contraception while being treated with PROLIA ® and for at least 5 months after stopping treatment with PROLIA ®. If you become pregnant during treatment with PROLIA ® or less than 5 months after stopping treatment with PROLIA ®, please inform your doctor. It is not known whether PROLIA ® is excreted in breast milk. It is important to tell your doctor if you are breastfeeding or plan to do so. Your doctor will then help you decide whether to stop breastfeeding, or whether to stop taking PROLIA ®, considering the benefit of breastfeeding to the baby and the benefit of PROLIA ® to the mother. If you are breastfeeding during PROLIA ® treatment, please inform your doctor.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
PROLIA ® has no or negligible influence on the ability to drive and use machines.

PROLIA ® contains sorbitol
This medicine contains 47 mg sorbitol in each ml of solution. If you have been told that you have an intolerance to some sugars, you should not take PROLIA ®.

PROLIA ® contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per 60 mg, that is to say essentially ‘sodium-free’.

The recommended dose is one pre-filled syringe of 60 mg administered once every 6 months, as a single injection under the skin (subcutaneous). The best places to inject are the top of your thighs and the abdomen. Your carer can also use the outer area of your upper arm. Please consult your doctor on the date for a potential next injection.

Each pack of PROLIA ® contains a reminder card, that can be removed from the carton and used to keep a record of the next injection date. You should also take calcium and vitamin D supplements while being on treatment with PROLIA ®. Your doctor will discuss this with you.

Your doctor may decide that it is best for you or a carer to inject PROLIA ®. Your doctor or healthcare provider will show you or your carer how to use PROLIA ®. For instructions on how to inject PROLIA ®, please read the section at the end of this leaflet.

Do not shake.

If you forget to use PROLIA ®
If a dose of PROLIA ® is missed, the injection should be administered as soon as possible. Thereafter, injections should be scheduled every 6 months from the date of the last injection.

If you stop using PROLIA ®
To get the most benefit from your treatment in reducing the risk of fractures, it is important to use PROLIA ® for as long as your doctor prescribes it for you. Do not stop your treatment without contacting your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will get them. Uncommonly, patients receiving PROLIA ® may develop skin infections (predominantly cellulitis). Please tell your doctor immediately if you develop any of these symptoms while being on treatment with PROLIA ®: swollen, red area of skin, most commonly in the lower leg, that feels hot and tender, and possibly with symptoms of fever.

Rarely, patients receiving PROLIA ® may develop pain in the mouth and/or jaw, swelling or non-healing of sores in the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. These could be signs of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediately if you experience such symptoms while being treated with PROLIA ® or after stopping treatment.

Rarely, patients receiving PROLIA ® may have low calcium levels in the blood (hypocalcaemia); severely low blood calcium levels may lead to hospitalisation and may even be life-threatening. Symptoms include spasms, twitches, or cramps in your muscles, and/or numbness or tingling in your fingers, toes or around your mouth and/or seizures, confusion, or loss of consciousness. If any of these apply to you, tell your doctor immediately. Low calcium in the blood may also lead to a change in heart rhythm called QT prolongation which is seen by electrocardiogram (ECG).

Rarely unusual fractures of the thigh bone may occur in patients receiving PROLIA ®. Contact your doctor if you experience new or unusual pain in your hip, groin or thigh as this may be an early indication of a possible fracture of the thigh bone.

Rarely, allergic reactions may occur in patients receiving PROLIA ®. Symptoms include swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin, wheezing or difficulty breathing. Please tell your doctor if you develop any of these symptoms while being treated with PROLIA ®.

Very common side effects (may affect more than 1 in 10 people):

• bone, joint, and/or muscle pain which is sometimes severe,
• arm or leg pain (pain in extremity).

Common side effects (may affect up to 1 in 10 people):

• painful urination, frequent urination, blood in the urine, inability to hold your urine,
• upper respiratory tract infection,
• pain, tingling or numbness that moves down your leg (sciatica),
• constipation,
• abdominal discomfort,
• rash,
• skin condition with itching, redness and/or dryness (eczema),
• hair loss (alopecia).

Uncommon side effects (may affect up to 1 in 100 people):

• fever, vomiting and abdominal pain or discomfort (diverticulitis),
• ear infection,
• rash that may occur on the skin or sores in the mouth (lichenoid drug eruptions).

Very rare side effects (may affect up to 1 in 10 000 people):

• allergic reaction that can damage blood vessels mainly in the skin (e.g. purple or brownish-red spots, hives or skin sores) (hypersensitivity vasculitis).

Not known (frequency cannot be estimated from the available data):

• talk to your doctor if you have ear pain, discharge from the ear and/or an ear infection. These could be signs of bone damage in the ear.

Reporting of side effects
If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of PROLIA ®. Alternatively, suspected side effects can be reported via our distributor, Aspen Pharmacare (Pty) Ltd: Tel: +27 800 118 088 Email: [email protected] / [email protected]

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 label and carton after EXP. The expiry date refers to the last day of that month. Store at or between 2 °C - 8 °C (in a refrigerator). Do not freeze. Keep the container in the outer carton in order to protect from light. Your pre-filled syringe may be left outside the refrigerator to reach room temperature (up to 25 °C) before injection. This will make the injection more comfortable. Once your syringe has been left to reach room temperature (up to 25 °C), it must be used within 30 days.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.