Instructions for Prolia (Denosumab) 60 mg
Release form
Solution for injection
Description:
The solution for injection is transparent, from colourless to light yellow, practically free from visible inclusions.
1 syringe 1 ml
denozumab 60 mg 60 mg
Auxiliary substances: sorbitol (E420) 47 mg
acetic acid ice 1 mg,
sodium hydroxide up to pH 5.0 - 5.5,
polysorbate 20 0.1 mg,
water d/i up to 1 ml
1 ml - disposable syringes (1) pre-filled - cardboard packs.
ATC codes
M05BX04 Denosumab
Clinical-pharmacological groups / Group affiliation
Bone tissue resorption inhibitor. Monoclonal antibody
Active substance
denozumab
Pharmacotherapy group:
Other drugs Prolia that affect bone structure and mineralization. Monoclonal antibodies
Storage Conditions
Store at 2-8°C. Do not freeze. Store in original packaging to protect against light.
Don't shake. Keep away from children!
Once removed from the fridge, the Prolya can be stored at room temperature no higher than 25°C in its original packaging for a maximum of 30 days.
Best before date
Shelf life is 3 years.
Pharmacological effect:
Denosumab is an all-human monoclonal antibody (IgG2) with high affinity and ligand specificity of the kappa B nuclear factor activator (RANKL) receptor and thus prevents the activation of the only RANKL receptor, the kV nuclear factor activator (RANK) located on the surface of osteoclasts and their precursors. Thus, preventing the RANKL/RANK interaction inhibits the formation, activation, and lifetime of osteoclasts. As a result, denosumab reduces bone resorption and increases the mass and strength of the cortical and trabecular layers of the bone.
Pharmacodynamic effects Denosumab:
The administration of denosumab at a dose of 60 mg resulted in a rapid reduction of serum concentrations of the bone resorption marker 1C telopeptide (STH) by approximately 70% within 6 hours of administration and approximately 85% over the next 3 days. The reduction in FSH remained stable in the 6-month interval between dosing. The rate of reduction of serum STH decreased in part with a reduction in serum denosumab concentration, reflecting the reversibility of denosumab's effect on bone remodeling.
These effects were observed throughout the course of treatment. Accordingly, the physiological relationship between the formation and resorption processes in bone tissue remodeling has shown a reduction in bone formation markers (e.g. bone-specific alkaline phosphatase and serum N-terminal collagen type 1 propeptide) from the first month following the introduction of the first dose of denosumab.
Bone remodeling markers (bone formation and bone resorption markers) typically reached pre-treatment concentrations no later than 9 months after the last dose. After the resumption of denosumab treatment, the degree of reduction in FSH concentrations was similar to the degree of reduction in FSH concentration at the beginning of denosumab treatment.
It has been shown that conversion from a treatment with alendron acid (average duration of use - 3 years) to denosumab results in an additional reduction in serum STH concentration compared to the group of women in postmenopause with low bone mass who continued treatment with alendron acid. At the same time, changes in serum calcium were the same in both groups.
In experimental studies, inhibition of RANK/RANKL at the same time as binding of osteoprotegerin to the Fc-fragment (OPG-Fc) resulted in slower bone growth and impaired teething. Therefore, denosumab treatment can inhibit the growth of bones with open growth areas in children and lead to impaired teething.
Immunogenicity
Denosumab is a human monoclonal antibody, so, as with other drugs Prolia of protein nature, there is a theoretical risk of immunogenicity. More than 13,000 patients were screened for antibody binding using the sensitive electrochemiluminescence technique in combination with immunological analysis. Less than 1% of patients who took denosumab for 5 years had antibodies (including pre-existing, transitive, and growing).
Seropositive patients were further screened for neutralizing antibodies, using chemiluminescence analysis in in vitro culture, neutralizing antibodies were not detected. No changes in pharmacokinetic profile, toxic profile or clinical response were identified due to antibody formation.
Clinical effectiveness
Treatment of osteoporosis in postmenopause
In women with postmenopausal osteoporosis, Prolia increases bone mineral density (MPC), reduces the incidence of hip fractures, vertebral and non-verbal fractures. The efficacy and safety of denosumab in the treatment of postmenopausal osteoporosis was proven in a study lasting 3 years. The results of the study show that denosumab significantly, in comparison with placebo reduces the risk of vertebral and nonverbal fractures, hip fractures in women with osteoporosis in postmenopause. The study included 7,808 women, of whom 23 per cent had frequent fractures in their vertebrae. All three efficiency endpoints in fracture relationships reached statistically significant values as measured by
The reduction of the risk of new vertebral fractures during the use of denosumab for more than 3 years remained stable and significant. The risk was reduced regardless of the 10-year probability of major osteoporotic fractures. The risk reduction was also not affected by frequent fractures of the vertebrae in the anamnesis, non-verbal fractures, age, patients, MPC, bone remodeling and prior osteoporosis therapy.
In postmenopausal women over 75, denosumab decreased the incidence of new vertebral fractures, and, according to post hoc analysis, decreased the incidence of hip fractures.
The decrease in the incidence of non-verbal fractures was observed irrespective of the 10-year probability of major osteoporotic fractures.
Denosumab significantly increased MPC in all anatomical regions compared to placebo. MPC was determined 1 year, 2 and 3 years after the start of therapy. Similar effects on MPC are found in the lumbar spine, regardless of age, race, body mass index (BMI), MPC and bone remodeling.
Histological studies confirmed normal bone architectonics and, as expected, a reduction in bone remodeling compared to placebo. No pathological changes have been observed, including fibrosis, osteomalination and bone architectonics disorders.
Clinical efficacy in the treatment of bone loss caused by hormone-deprivation therapy or aromatase inhibitors
Treatment of bone loss caused by androgen deprivation
The efficacy and safety of denosumab in the treatment of bone loss associated with reduced androgen concentrations were proven in a 3-year study involving 1,468 patients with non-metastatic prostate cancer.
Significant increases in MPC were determined in the lumbar spine, the entire femur, the femur neck, the femur spinner 1 month after the first dose. The increase in MPC in the lumbar spine was not dependent on age, race, geographical region, BMI, initial values of MPC, bone remodeling; duration of hormone-deprivation therapy and the presence of a vertebral fracture in the anamnesis.
Denosumab significantly reduced the risk of new vertebral fractures during 3 years of use. Risk reduction was observed 1 year and 2 years after the start of therapy. Denosumab also reduced the risk of more than one osteoporotic fracture in any location.
Bone loss treatment in women treated with aromatase inhibitors for breast cancer
The efficacy and safety of denosumab in treating bone loss caused by adjuvant therapy with an aromatase inhibitor was assessed in a 2-year study involving 252 patients with non-metastatic breast cancer. Denosumab significantly increased MPC in all anatomical regions, compared to placebo, for 2 years. An increase in MPC was observed in the lumbar spine a month after the first dose. Positive effects on MPC in the lumbar spine were noted regardless of age, duration of aromatase inhibitor therapy, BMI prior to chemotherapy, prior use of selective estrogen receptor modulator (SMRE) and time elapsed from the beginning of menopause.
Testimony Denosumab:
- treatment of postmenopausal osteoporosis;
- Treatment of bone loss in women treated with aromatase inhibitors for breast cancer and in men with prostate cancer treated with hormone-deprivation therapy.
Method of use, course and dosage
Introduction
The injection of the drug Prolia requires prior training - see the recommendations for drug Prolia administration at the end of this instruction.
The recommended dose of Prolya is one p/k injection of 60 mg every 6 months. During the course of treatment, it is recommended to take additional calcium and vitamin D.
Children
Prolya is not recommended for use in pediatrics because its efficacy and safety have not been studied in this age group.
Elderly patients
Based on the available data on the effectiveness and safety of the drug Denosumab in this age group, no correction of the dosage regimen of the drug is required.
Kidney failure
Based on the available data on the effectiveness and safety of the drug Prolia in this group of patients, no correction of the dosage regimen of the drug is required.
Patients with severe renal failure (creatinine clearance <30 ml/min) or on dialysis are at high risk of developing hypocalciemia. These patients need to take calcium and vitamin D supplements.
Liver failure
Effectiveness and safety were not studied.
Usage Guidelines
You should evaluate the solution before applying for inclusions or color changes. The solution cannot be used when a color is clouded or changed. Don't shake.
To avoid discomfort at the injection site, warm the solution to room temperature (up to 25°C) before injection and then slowly inject all the contents of the pre-filled syringe. Throw away the syringe with the rest of the drug Prolia.
Any quantities of unused medicine or unused materials must be destroyed according to local requirements
Side Effect
Data derived from controlled use in clinical trials.
Adverse reactions are listed by organ system class in terms of the MedDRA.
The incidence of adverse events was classified as follows: very often (≥1/10), often (≥1/100, <1/10), sometimes (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), very rarely (<1/10 000), including some cases.
In each group of organ systems and frequency of messages, unwanted reactions are given in descending order of severity.
Class of organ system Frequency Adverse reaction
Infections and infestations Infrequent subcutaneous inflammation
From the metabolic and electrolytic side Very rarely hypocalcemia
From the viewpoint Frequently cataract in men receiving androgen-deprivation therapy for prostate cancer
Skin and subcutaneous fat Infrequent eczema including dermatitis, allergic dermatitis, atopic dermatitis, contact dermatitis
From the side of the musculoskeletal system and connective tissue Frequently
Rarely Limb pain
Osteonecrosis of the jaw
Special Instructions:
It is recommended to take calcium and vitamin D during the use of Prolya.
Hypocalcemia can be corrected by taking calcium and vitamin D in adequate doses before starting denosumab therapy. Control of calcium concentration in patients predisposed to hypocalcemia is recommended.
Patients treated with Prolya may develop skin and appendage infections (mainly subcutaneous inflammation) that may require hospitalization in some cases. Such reactions were more commonly reported for the denosumab group (0.4%) than the placebo group (0.1%). The total incidence of skin infections is comparable in the denosumab and placebo groups. Patients should be instructed to seek immediate medical attention in case of developing symptoms and signs of subcutaneous inflammation.
In patients with common cancer who received 120 mg of denosumab every 4 weeks, the development of cases of osteonecrosis of the jaw was reported. There are isolated reports of oral osteonecrosis developing at a dose of 60 mg every 6 months.
Persons with a latex allergy should not touch a rubber needle cap (a latex derivative).
Influence on the ability to control vehicles and machinery
No studies have been conducted on the impact on the ability to drive vehicles and to control machinery.
Use in liver disorders
Effectiveness and safety were not studied.
Terms of Sale
The drug Denosumab is prescription.
Application in elderly patients
Based on the available data on the effectiveness and safety of the drug Denosumab in this age group, no correction of the dosage regimen of the drug Prolia is required.
Use in children
Prolya is not recommended for use in pediatrics because its efficacy and safety have not been studied in this age group.
Nosology (ICD codes)
C50
Malignant breast neoplasm
C61
Malignant prostate neoplasm
M80.0
Postmenopausal osteoporosis with pathological fracture
M80.1
Osteoporosis with pathological fracture after ovarian removal
M81.0
Postmenopausal osteoporosis
M81.1
Osteoporosis after ovarian removal