IMPORTANT SAFETY INFORMATION

WARNING: SEVERE LOW CALCIUM LEVELS IN PATIENTS WITH ADVANCED KIDNEY DISEASE

If you have advanced chronic kidney disease (may or may not be on kidney dialysis), BOSAYA may increase your risk for severe low calcium levels in your blood, which could result in hospitalization, life-threatening events and death. A mineral and bone disorder associated with kidney disease called chronic kidney disease-mineral bone disorder (CKD-MBD) may increase your risk for severe low calcium levels in blood. Before you start BOSAYA and during treatment, your doctor may need to do certain blood tests to check for CKD-MBD.

Do not take BOSAYA if you:

• Have been told by your doctor that your blood calcium level is too low.
• Are pregnant or plan to become pregnant.
• Are allergic to denosumab products or any of the ingredients in BOSAYA.

What is the most important information I should know about BOSAYA?

If you receive BOSAYA, you should not receive other denosumab products.

BOSAYA can cause serious side effects including:

• Increased risk of severe low calcium levels in your blood (hypocalcemia). BOSAYA may lower the calcium levels in your blood. If you have low blood calcium before you start receiving BOSAYA, it may get worse during treatment. Your low blood calcium must be treated before you receive BOSAYA. Talk to your doctor before starting BOSAYA. Your doctor may prescribe calcium and vitamin D to help prevent low calcium levels in your blood while you take BOSAYA. Take calcium and vitamin D as your doctor tells you to.

If you have advanced chronic kidney disease (may or may not be on kidney dialysis), BOSAYA may increase your risk for severe low calcium levels in your blood, which could result in hospitalization, life-threatening events and death. A mineral and bone disorder associated with kidney disease called chronic kidney disease-mineral bone disorder (CKD-MBD) may increase your risk for severe low calcium levels in blood. Before you start BOSAYA and during treatment, your doctor may need to do certain blood tests to check for CKD-MBD.

Most people with low blood calcium levels do not have symptoms, but some people may have symptoms. Call your doctor right away if you have symptoms of low blood calcium such as:

• Spasms, twitches, or cramps in your muscles.
• Numbness or tingling in your fingers, toes, or around your mouth.

• Serious allergic reactions. Serious allergic reactions have happened in people who take denosumab products. Call your doctor or go to your nearest emergency room right away if you have any symptoms of a serious allergic reaction, including low blood pressure (hypotension); trouble breathing; throat tightness; swelling of your face, lips, or tongue; rash; itching; or hives.

• Severe jawbone problems (osteonecrosis). Severe jawbone problems may happen when you take BOSAYA. Your doctor should examine your mouth before you start BOSAYA. Your doctor may tell you to see your dentist before you start BOSAYA. It is important for you to practice good mouth care during treatment with BOSAYA.

• Unusual thigh bone fractures. Some people have developed unusual fractures in their thigh bone. Symptoms of a fracture include new or unusual pain in your hip, groin, or thigh.

• Increased risk of broken bones, including broken bones in the spine, after stopping, skipping, or delaying BOSAYA. Talk with your doctor before starting BOSAYA treatment. After your treatment with BOSAYA is stopped, or if you skip or delay taking a dose, your risk for breaking bones, including bones in your spine, is increased. Your risk for having more than 1 broken bone in your spine is increased if you have already had a broken bone in your spine. Do not stop, skip, or delay taking BOSAYA without first talking with your doctor. If your BOSAYA treatment is stopped, talk to your doctor about other medicine that you can take.

• Serious infections. Serious infections in your skin, lower stomach area (abdomen), bladder, or ear may happen if you take BOSAYA. Inflammation of the inner lining of the heart (endocarditis) due to an infection also may happen more often in people who take BOSAYA. You may need to go to the hospital for treatment if you develop an infection.

BOSAYA is a medicine that may affect the ability of your body to fight infections. People who have a weakened immune system or take medicines that affect the immune system may have an increased risk for developing serious infections. Call your doctor right away if you have any of the following symptoms of infection:

• Fever or chills.
• Skin that looks red or swollen and is hot or tender to touch.
• Fever, shortness of breath, cough that will not go away.
• Severe abdominal pain.
• Frequent or urgent need to urinate or burning feeling when you urinate.

• Skin problems. Skin problems such as inflammation of your skin (dermatitis), rash, and eczema may happen if you take BOSAYA. Call your doctor if you have any of the following symptoms of skin problems that do not go away or get worse: redness; itching; small bumps or patches (rash); your skin is dry or feels like leather; blisters that ooze or become crusty; or skin peeling.

• Bone, joint, or muscle pain. Some people who take denosumab products develop severe bone, joint, or muscle pain.

Call your doctor right away if you have any of these side effects.

What should I tell my doctor BEFORE starting BOSAYA?

Tell your doctor about all of your medical conditions, including if you:

• Are taking other denosumab products.
• Have low blood calcium.
• Cannot take daily calcium and vitamin D.
• Had parathyroid or thyroid surgery (glands located in your neck).
• Have been told you have trouble absorbing minerals in your stomach or intestines (malabsorption syndrome).
• Have kidney problems or are on kidney dialysis.
• Are taking medicine that can lower your blood calcium levels.
• Plan to have dental surgery or teeth removed.
• Are pregnant or plan to become pregnant. BOSAYA may harm your unborn baby.

Females who are able to become pregnant:

• Your healthcare provider should do a pregnancy test before you start treatment with BOSAYA.
• You should use an effective method of birth control (contraception) during treatment with BOSAYA and for at least 5 months after your last dose of BOSAYA.
• Tell your doctor right away if you become pregnant while taking BOSAYA.

• Are breastfeeding or plan to breastfeed. It is not known if BOSAYA passes into your breast milk. You and your doctor should decide if you will take BOSAYA or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of BOSAYA?

BOSAYA may cause serious side effects.

It is not known if the use of BOSAYA over a long period of time may cause slow healing of broken bones.

The most common side effects of BOSAYA in women who are being treated for osteoporosis after menopause are back pain, pain in your arms and legs, high cholesterol, muscle pain, and bladder infection. The most common adverse reactions leading to discontinuation in patients with postmenopausal osteoporosis are back pain and constipation.

The most common side effects of BOSAYA in men with osteoporosis are back pain, joint pain, and common cold (runny nose or sore throat).

The most common side effects of BOSAYA in patients with glucocorticoid-induced osteoporosis are back pain, high blood pressure, lung infection (bronchitis), and headache.

The most common side effects of BOSAYA in patients receiving certain treatments for prostate or breast cancer are joint pain, back pain, pain in your arms and legs, and muscle pain. Additionally, in denosumab-treated men with nonmetastatic prostate cancer receiving androgen deprivation therapy (ADT), a greater incidence of cataracts was observed.

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of BOSAYA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.