Prolia (Page 8 of 9)

14.5 Treatment of Bone Loss in Women with Breast Cancer

The efficacy and safety of Prolia in the treatment of bone loss in women receiving adjuvant aromatase inhibitor (AI) therapy for breast cancer was assessed in a 2-year, randomized (1:1), double-blind, placebo-controlled, multinational study. Women had baseline BMD T-scores between -1.0 to -2.5 at the lumbar spine, total hip, or femoral neck, and had not experienced fracture after age 25. The mean baseline lumbar spine BMD T-score was -1.1, and 2.0% of women had a vertebral fracture at baseline. The 252 women enrolled ranged in age from 35 to 84 years (median 59 years). Women were randomized to receive subcutaneous injections of either placebo (n = 125) or Prolia 60 mg (n = 127) once every 6 months for a total of 4 doses. Randomization was stratified by duration of adjuvant AI therapy at trial entry (≤ 6 months vs. > 6 months). Sixty-two percent of patients received adjuvant AI therapy for more than 6 months at study entry. All women received at least 1000 mg calcium and 400 IU vitamin D supplementation daily.

Effect on Bone Mineral Density (BMD)

The primary efficacy variable was percent change in lumbar spine BMD from baseline to month 12. Lumbar spine BMD was higher at 12 months in Prolia-treated patients as compared to placebo-treated patients [-0.7% placebo, +4.8% Prolia; treatment difference 5.5% (95% CI: 4.8, 6.3); p < 0.0001].

With approximately 81% of patients followed for 2 years, treatment differences in BMD at 2 years were 7.6% (-1.4% placebo, +6.2% Prolia) at the lumbar spine, 4.7% (-1.0% placebo, +3.8% Prolia) at the total hip, and 3.6% (-0.8% placebo, +2.8% Prolia) at the femoral neck.

16 HOW SUPPLIED/STORAGE AND HANDLING

Prolia is supplied in a single-dose prefilled syringe with a safety guard. The gray needle cap on the single-dose prefilled syringe contains dry natural rubber (a derivative of latex).

60 mg/1 mL in a single-dose prefilled syringe

1 per carton

NDC 55513-710-01

Store Prolia in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Prior to administration, Prolia may be allowed to reach room temperature (up to 25°C/77°F) in the original container. Once removed from the refrigerator, Prolia must not be exposed to temperatures above 25°C/77°F and must be used within 14 days. If not used within the 14 days, Prolia should be discarded. Do not use Prolia after the expiry date printed on the label.

Protect Prolia from direct light and heat.

Avoid vigorous shaking of Prolia.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Drug Products with Same Active Ingredient

Advise patients that denosumab is also marketed as Xgeva, and if taking Prolia, they should not receive Xgeva [see Warnings and Precautions (5.1)].

Hypersensitivity

Advise patients to seek prompt medical attention if signs or symptoms of hypersensitivity reactions occur. Advise patients who have had signs or symptoms of systemic hypersensitivity reactions that they should not receive denosumab (Prolia or Xgeva) [see Warnings and Precautions (5.2), Contraindications (4)].

Hypocalcemia

Advise the patient to adequately supplement with calcium and vitamin D and instruct them on the importance of maintaining serum calcium levels while receiving Prolia [see Warnings and Precautions (5.3), Use in Specific Populations (8.6)]. Advise patients to seek prompt medical attention if they develop signs or symptoms of hypocalcemia.

Osteonecrosis of the Jaw

Advise patients to maintain good oral hygiene during treatment with Prolia and to inform their dentist prior to dental procedures that they are receiving Prolia. Patients should inform their physician or dentist if they experience persistent pain and/or slow healing of the mouth or jaw after dental surgery [see Warnings and Precautions (5.4)].

Atypical Subtrochanteric and Diaphyseal Femoral Fractures

Advise patients to report new or unusual thigh, hip, or groin pain [see Warnings and Precautions (5.5)].

Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia Treatment

Advise patients not to interrupt Prolia therapy without talking to their physician [see Warnings and Precautions (5.6)].

Serious Infections

Advise patients to seek prompt medical attention if they develop signs or symptoms of infections, including cellulitis [see Warnings and Precautions (5.7)].

Dermatologic Adverse Reactions

Advise patients to seek prompt medical attention if they develop signs or symptoms of dermatological reactions (dermatitis, rashes, and eczema) [see Warnings and Precautions (5.8)].

Musculoskeletal Pain

Inform patients that severe bone, joint, and/or muscle pain have been reported in patients taking Prolia. Patients should report severe symptoms if they develop [see Warnings and Precautions (5.9)].

Pregnancy/Nursing

Counsel females of reproductive potential to use effective contraceptive measure to prevent pregnancy during treatment and for at least 5 months after the last dose of Prolia. Advise the patient to contact their physician immediately if pregnancy does occur during these times. Advise patients not to take Prolia while pregnant or breastfeeding. If a patient wishes to start breastfeeding after treatment, advise her to discuss the appropriate timing with her physician [see Contraindications (4), Use in Specific Populations (8.1)].

Schedule of Administration

Advise patients that if a dose of Prolia is missed, the injection should be administered as soon as convenient. Thereafter, schedule injections every 6 months from the date of the last injection.

Prolia^® (denosumab)

Manufactured by:
Amgen Inc.
One Amgen Center DriveThousand Oaks, California 91320-1799

Patent: http://pat.amgen.com/prolia/

© 2010-2021 Amgen Inc. All rights reserved.

1xxxxxx – v21

This Medication Guide has been approved by the U.S. Food and Drug Administration.			Revised: 10/2019
Medication GuideProlia® (PRÓ-lee-a)(denosumab)Injection, for subcutaneous use
What is the most important information I should know about Prolia?
If you receive Prolia, you should not receive XGEVA ® . Prolia contains the same medicine as Xgeva (denosumab).Prolia can cause serious side effects including: Serious allergic reactions. Serious allergic reactions have happened in people who take Prolia. Call your doctor or go to your nearest emergency room right away if you have any symptoms of a serious allergic reaction. Symptoms of a serious allergic reaction may include:
	low blood pressure (hypotension) trouble breathing throat tightness swelling of your face, lips, or tongue	rash itching hives
Low calcium levels in your blood (hypocalcemia). Prolia may lower the calcium levels in your blood. If you have low blood calcium before you start receiving Prolia, it may get worse during treatment. Your low blood calcium must be treated before you receive Prolia. 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 Your doctor may prescribe calcium and vitamin D to help prevent low calcium levels in your blood while you take Prolia. Take calcium and vitamin D as your doctor tells you to. Severe jaw bone problems (osteonecrosis). Severe jaw bone problems may happen when you take Prolia. Your doctor should examine your mouth before you start Prolia. Your doctor may tell you to see your dentist before you start Prolia. It is important for you to practice good mouth care during treatment with Prolia. Ask your doctor or dentist about good mouth care if you have any questions. 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 Prolia. Talk with your doctor before starting Prolia treatment. After your treatment with Prolia 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 Prolia without first talking with your doctor. If your Prolia 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 Prolia. Inflammation of the inner lining of the heart (endocarditis) due to an infection also may happen more often in people who take Prolia. You may need to go to the hospital for treatment if you develop an infection. Prolia 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 Prolia. 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 skin peeling
Bone, joint, or muscle pain. Some people who take Prolia develop severe bone, joint, or muscle pain. Call your doctor right away if you have any of these side effects.
What is Prolia? Prolia is a prescription medicine used to: Treat osteoporosis (thinning and weakening of bone) in women after menopause (“change of life”) who: are at high risk for fracture (broken bone) cannot use another osteoporosis medicine or other osteoporosis medicines did not work well Increase bone mass in men with osteoporosis who are at high risk for fracture. Treat osteoporosis in men and women who will be taking corticosteroid medicines (such as prednisone) for at least 6 months and are at high risk for fracture. Treat bone loss in men who are at high risk for fracture receiving certain treatments for prostate cancer that has not spread to other parts of the body. Treat bone loss in women who are at high risk for fracture receiving certain treatments for breast cancer that has not spread to other parts of the body. It is not known if Prolia is safe and effective in children.
Do not take Prolia 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 or any of the ingredients in Prolia. See the end of this Medication Guide for a complete list of ingredients in Prolia.
Before taking Prolia, tell your doctor about all of your medical conditions, including if you: are taking a medicine called Xgeva (denosumab). Xgeva contains the same medicine as Prolia. 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. Prolia 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 Prolia. You should use an effective method of birth control (contraception) during treatment with Prolia and for at least 5 months after your last dose of Prolia. Tell your doctor right away if you become pregnant while taking Prolia. are breastfeeding or plan to breastfeed. It is not known if Prolia passes into your breast milk. You and your doctor should decide if you will take Prolia 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. Know the medicines you take. Keep a list of medicines with you to show to your doctor or pharmacist when you get a new medicine.
How will I receive Prolia? Prolia is an injection that will be given to you by a healthcare professional. Prolia is injected under your skin (subcutaneous). You will receive Prolia 1 time every 6 months. You should take calcium and vitamin D as your doctor tells you to while you receive Prolia. If you miss a dose of Prolia, you should receive your injection as soon as you can. Take good care of your teeth and gums while you receive Prolia. Brush and floss your teeth regularly. Tell your dentist that you are receiving Prolia before you have dental work.
What are the possible side effects of Prolia?Prolia may cause serious side effects. See “What is the most important information I should know about Prolia?“ It is not known if the use of Prolia over a long period of time may cause slow healing of broken bones. The most common side effects of Prolia in women who are being treated for osteoporosis after menopause are:
	back pain pain in your arms and legs high cholesterol	muscle pain bladder infection
The most common side effects of Prolia in men with osteoporosis are:
	back pain joint pain	common cold (runny nose or sore throat)
The most common side effects of Prolia in patients with glucocorticoid-induced osteoporosis are:
	back pain high blood pressure	lung infection (bronchitis) headache
The most common side effects of Prolia in patients receiving certain treatments for prostate or breast cancer are:
	joint pain back pain	pain in your arms and legs muscle pain
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 Prolia. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Prolia if I need to pick it up from a pharmacy? Keep Prolia in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton. Do not freeze Prolia. When you remove Prolia from the refrigerator, Prolia must be kept at room temperature [up to 77°F (25°C)] in the original carton and must be used within 14 days. Do not keep Prolia at temperatures above 77°F (25°C). Warm temperatures will affect how Prolia works. Do not shake Prolia. Keep Prolia in the original carton to protect from light. Keep Prolia and all medicines out of the reach of children.
General information about the safe and effective use of Prolia. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Prolia for a condition for which it was not prescribed. Do not give Prolia to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about Prolia that is written for health professionals.
What are the ingredients in Prolia? Active ingredient: denosumabInactive ingredients: sorbitol, acetate, polysorbate 20, Water for Injection (USP), and sodium hydroxideAmgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-17991xxxxxx – v15 For more information, go to www.Prolia.com or call Amgen at 1-800-772-6436.