PROLIA 60 MG SYRINGE is a prescription medicine used to treat osteoporosis in women after menopause who are at high risk for fracture or cannot use another osteoporosis medicine or other osteoporosis medicines did not work well.

PROLIA 60 MG SYRINGE is used to increase bone mass in men with osteoporosis who are at high risk for fracture.

treats osteoporosis in men and women who will be taking corticosteroid medicines (such as prednisone) for at least six months and are at high risk for fracture.

It decreases bone loss in men who are at high risk for fracture by receiving certain treatments for prostate cancer that has not spread to other parts of the body.

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.

Active ingredient of PROLIA 60 MG SYRINGE

Densumab

Indications of PROLIA 60 MG SYRINGE

PROLIA 60 MG SYRINGE is a prescription medicine used to treat osteoporosis in women after menopause who are at high risk for fracture or cannot use another osteoporosis medicine or other osteoporosis medicines did not work well.
PROLIA 60 MG SYRINGE used to increase bone mass in men with osteoporosis who are at high risk for fracture.
treats osteoporosis in men and women who will be taking corticosteroid medicines (such as prednisone) for at least six months and are at high risk for fracture.
It decreases 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.
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.

How PROLIA 60 MG SYRINGE works?

PROLIA 60 MG SYRINGE ^® is a targeted treatment that stops bone-removing cells before they can reach and damage the bone.

^{PROLIA 60 MG SYRINGE ®} is an injection that works with your body to help stop the development of bone-removing cells.

Precautions when using PROLIA 60 MG SYRINGE

Do not take PROLIA 60 MG SYRINGE if you: have low blood calcium; or are pregnant or plan to become pregnant, as Prolia® may harm your unborn baby; or are allergic to denosumab or any ingredients in Prolia.

What is the most important information I should know about PROLIA 60 MG SYRINGE ?

If you receive Prolia, you should not receive XGEVA. Prolia contains the same active ingredient as XGEVA (denosumab).

Before taking PROLIA 60 MG SYRINGE ®, tell your doctor about all of your medical conditions, including if you:

Take the medicine XGEVA (denosumab)
Have low blood calcium
Cannot take daily calcium and vitamin D
Had parathyroid or thyroid surgery (glands located in your neck)
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
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 breast-feeding or plan to breast-feed

What are the possible side effects of PROLIA 60 MG SYRINGE ?

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 being treated for osteoporosis after menopause are back pain, pain in your arms and legs, high cholesterol, muscle pain, and bladder infection.

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

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

Joint pain, back pain, pain in your arms and legs, and muscle pain. Additionally, in Prolia®-treated men with non-metastatic prostate cancer receiving ADT, a greater incidence of cataracts was observed.

Hypocalcemia
Serious Infections
Dermatologic Adverse Reactions
Osteonecrosis of the Jaw
Atypical Sub trochanteric and Diaphyseal Femoral Fractures
Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia Treatment

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, including low blood pressure (hypotension); trouble breathing; throat tightness; swelling of your face, lips, or tongue; rash; itching; or hives.

Low blood calcium (hypocalcemia).

Prolia® may lower the calcium levels in your blood. If you have low blood calcium, it may get worse during treatment.

you must get treatment for your low blood calcium before you receive Prolia®.

Take calcium and vitamin D as your doctor tells you to help prevent low blood calcium.

Severe jaw bone problems (osteonecrosis) may occur. Your doctor should examine your mouth before you start Prolia® and may tell you to see your dentist. It is important for you to practice good mouth care during treatment with Prolia®.

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 finishing your treatment with Prolia, or if you skip or delay taking a dose, it will increase your risk for breaking bones, including bones in your spine.
This will increase the risk for having more than 1 broken bone in your spine. 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.
Serious infections in your skin, lower stomach area (abdomen), bladder, or ear may happen. Inflammation of the inner lining of the heart (endocarditis) due to an infection may also happen more often in people who take PROLIA 60 MG SYRINGE. You may need to go to the hospital for treatment.
PROLIA 60 MG SYRINGE is a medicine that may affect the ability of your body to fight infections. People who have weakened immune systems or take medicines that affect the immune system may have an increased risk for developing serious infections.
Skin problems such as inflammation of your skin (dermatitis), rash, and eczema.
Bone, joint, or muscle pain. Some people who take Prolia® develop severe bone, joint, or muscle pain.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnant women can’t use densumab because it may cause harm to a fetus.

There are insufficient data with denosumab use in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with

denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on

body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes,

abnormal bone growth, and decreased neonatal growth.

Lactation

There is no information regarding the presence of denosumab in human milk, the effects on the breastfed

infant, or the effects on milk production. Scientists found out densumab after testing the maternal milk of cynomolgus

monkeys up to 1 month after the last dose of denosumab (≤ 0.5% milk: serum ratio) and maternal

mammary gland development was normal, with no impaired lactation. However, pregnant RANKL

knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation.

Contraception

Females

Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of Prolia.

Males

Denosumab was present at low concentrations (approximately 2% of serum exposure) in the seminal fluid

of male subjects given Prolia. Following vaginal intercourse, the maximum amount of denosumab

delivered to a female partner would result in exposures approximately 11000 times lower than the

prescribed 60 mg subcutaneous dose, and at least 38 times slower than the NOEL in monkeys.

Therefore, male condom use would not be necessary as it is unlikely that a female partner or fetus would

be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid.

Pediatric Use

Prolia is not recommended in pediatric patients younger than age 4 years because of the high rates of
skeletal growth and the potential for Prolia to negatively affect long-bone growth and dentition. The
safety and effectiveness of Prolia in pediatric patients have not been established.
Treatment with Prolia may impair bone growth in children with open growth plates and may inhibit
eruption of dentition. In neonatal rats, inhibition of RANKL (the target of Prolia therapy) with a
construct of osteoprotegerin bound to Fc (OPG-Fc) at doses ≤ 10 mg/kg was associated with inhibition of
bone growth and tooth eruption. Adolescent primates treated with denosumab at doses 10 and 50 times
(10 and 50 mg/kg dose) higher than the recommended human dose of 60 mg administered every
6 months, based on body weight (mg/kg), had abnormal growth plates, considered to be consistent with

The pharmacological activity of denosumab in pediatrics

Cynomolgus monkeys exposed in utero to denosumab exhibited bone abnormalities, an absence of

axillary, inguinal, mandibular, and mesenteric lymph nodes, reduced hematopoiesis, tooth malalignment,

and decreased neonatal growth. Some bone abnormalities recovered once exposure was ceased following

birth; however, axillary and inguinal lymph nodes remained absent 6 months post-birth.

Geriatric Use

Of the total number of patients in clinical studies of Prolia, 9943 patients (76%) were ≥ 65 years old,

while 3576 (27%) were ≥ 75 years old. Of the patients in the osteoporosis study in men, 133 patients

(55%) were ≥ 65 years old, while 39 patients (16%) were ≥ 75 years old. Of the patients in the

glucocorticoid-induced osteoporosis study, 355 patients (47%) were ≥ 65 years old, while 132 patients

(17%) were ≥ 75 years old. No overall differences in safety or efficacy were observed between these

patients and younger patients, and other reported clinical experience has not identified differences in

responses between the elderly and younger patients, but greater sensitivity of some older individuals

cannot be ruled out.

Renal Impairment

No dose adjustment is necessary in patients with renal impairment.

In clinical studies, patients with severe renal impairment (creatinine clearance < 30 mL/min) or receiving

dialysis were at greater risk of developing hypocalcemia. Consider the benefit-risk profile when

administering Prolia to patients with severe renal impairment or receiving dialysis. Clinical monitoring of

calcium and mineral levels (phosphorus and magnesium) is highly recommended. Adequate intake of

calcium and vitamin D is important in patients with severe renal impairment or receiving dialysis.

Hepatic Impairment

No clinical studies have been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of Prolia.

OVERDOSAGE of PROLIA 60 MG SYRINGE

There is no experience with overdosage with Prolia.

CLINICAL PHARMACOLOGY

Mechanism of Action

Prolia binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and
survival of osteoclasts, the cells responsible for bone resorption. Prolia prevents RANKL from activating
its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK
interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and
increasing bone mass and strength in both cortical and trabecular bone.