Prolia - Instructions For Use Of The Drug, Reviews, Price, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Prolia

Prolia: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Prolia

ATX code: M05BX04

Active ingredient: denosumab (denosumab)

Manufacturer: Amgen Manufacturing Limited (Puerto Rico)

Description and photo updated: 12.07.2018

Prices in pharmacies: from 12336 rubles.

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Prolia - a drug that inhibits bone resorption; monoclonal antibody.

Release form and composition

Prolia is produced in the form of a solution for subcutaneous (s / c) administration: colorless or pale yellow, transparent, practically free from visible inclusions [1 ml each in a disposable pre-filled syringe (PZS) made of glass with a 27G stainless steel needle with elastomeric a plunger laminated with fluoropolymer (with or without a needle protector); in a contour acheikova package 1 labeled syringe, in a cardboard box 1 package or 1 syringe without packaging].

1 ml of solution (1 PZH) contains:

• active substance: denosumab - 60 mg;
• additional components: glacial acetic acid, sorbitol (E420), polysorbate 20, sodium hydroxide, water for injection.

Pharmacological properties

Pharmacodynamics

The active component of Prolia, denosumab, is a fully human monoclonal antibody (IgG2). This substance is characterized by a high degree of affinity (affinity) and specificity to the ligand of the nuclear factor kappa B (RANKL) activator receptor, which prevents the activation of the only RANKL receptor located on the surface of osteoclasts and their precursors, the nuclear factor kB activator (RANK). Denosumab, by blocking the RANKL / RANK interaction, counteracts the formation, increased activity and duration of the existence of osteoclasts, which leads to a decrease in bone resorption and an increase in the mass and strength of the cortical (outer) and trabecular (cancellous) layers of bone.

The administration of the active substance at a dose of 60 mg provided a rapid decrease in serum levels of 1C-telopeptide (CTX), which is a marker of bone resorption, within 6 hours after s.c. injection by about 70%, and during the next 3 days by about 85%. The reduced CTX concentration was stably maintained during the six-month interval between Prolia applications. With a decrease in the level of the substance in the blood serum, a partial decrease in the rate of decrease in the level of CTX was observed, which reflected the reversibility of the effect of denosumab on bone remodeling. These effects persisted throughout the entire therapeutic course. In accordance with the relationship between the formation and resorption of bone tissue during its remodeling, already from the first month after the first injection of the drug, a decrease in the number of markers of bone formation was noted,including bone-specific alkaline phosphatase (ALP) and serum N-terminal type I collagen propeptide.

Markers of bone formation and resorption (bone remodeling) in most cases reached the levels observed before the start of the course no later than 9 months after using the last dose of the drug. Upon resumption of denosumab therapy, the level of decrease in CTX corresponded to that after the first administration of Prolia.

In the course of the studies, it was demonstrated that the transfer from therapy with alendronic acid (course duration on average 3 years) to the use of denosumab in postmenopausal patients with low bone mass provides an additional decrease in serum CTX concentration when compared with a similar group of patients who continued to use alendronic acid. The detected changes in the level of calcium in serum were the same in both study groups.

Since denosumab belongs to human monoclonal antibodies, its use, like the use of other proteinaceous agents, could theoretically increase the risk of immunogenicity. Over 13,000 patients were recruited for examinations with the aim of detecting binding antibodies in them using immunological analysis, as well as the method of sensitive electrochemiluminescence. Antibodies (including transient, growing and pre-existing antibodies) were detected in less than 1% of patients during treatment with denosumab for 5 years. After further examination of seropositive patients, in order to detect neutralizing antibodies using the method of chemiluminescence analysis, these antibodies were not detected in the in vitro cell culture. The effect of antibody formation on the clinical effect,no toxic profile or pharmacokinetics were observed.

The drug Prolia in women with postmenopausal osteoporosis increases bone mineral density (BMD), which helps to reduce the incidence of vertebral and non-vertebral fractures, and hip fractures. In the course of studies, in which 7808 women took part over 3 years, the safety and efficacy of the drug in the treatment of postmenopausal osteoporosis was proved. According to the results of these studies, with this disease in women (23% of whom had previously had frequent vertebral fractures) during the use of denosumab, the risk of fractures was significantly reduced compared with the placebo group. For fractures, all three efficacy endpoints achieved statistically significant values, which were assessed using a previously established sequential test design.

With drug therapy for more than three years, the reduction in the risk of vertebral fractures was significant and stable. A decrease in risk was noted regardless of the age of patients, previous frequent vertebral fractures, non-vertebral fractures, BMD, level of bone remodeling, 10-year probability of major osteoporotic fractures, and previous therapy for osteoporosis.

In postmenopausal women over 75 years of age, Prolia treatment reduced the incidence of new cases of vertebral fractures and, according to the results obtained in post hoc analysis, reduced the incidence of fractures of the femoral neck.

A decrease in the occurrence of non-vertebral fractures was also observed regardless of the 10-year probability of occurrence of large osteoporotic fractures. Compared with placebo, denosumab significantly increased BMD in all anatomical areas, determined annually during the period of three years of therapy. In the lumbar region of the spine, a similar effect of Prolia on BMD was revealed, unaffected by age, race of the patient, BMI (body mass index), bone remodeling, BMD value. The results of histological studies indicated a normal structure of bones and a decrease in their remodeling in comparison with placebo, as well as the absence of such pathological changes as osteomalacia, fibrosis, and impaired bone architectonics.

Also, over three years of studies, which included 1468 patients with non-metastatic prostate cancer, the safety and effectiveness of Prolia in the treatment of bone loss associated with a decrease in the level of androgens in the body was demonstrated. One month after the administration of the first dose of the drug, a pronounced increase in BMD in the lumbar region of the spine, the entire femur, its neck and trochanter was revealed. This increase in BMD in the lumbar spine did not depend on race, BMI, age, geographic region, bone remodeling, initial BMD, a history of vertebral fracture, and the duration of hormone deprivation therapy.

The use of denosumab for 3 years (already after 1 and 2 years after the start of treatment) significantly reduced the threat of fresh vertebral fractures. The introduction of Prolia also reduced the risk of developing more than one osteoporotic fracture of various localization.

In the treatment of bone loss associated with adjuvant aromatase inhibitor therapy, the safety and efficacy of the active ingredient Prolia was assessed in a two-year study involving 252 patients with non-metastatic breast cancer. According to the results obtained, the agent, in comparison with placebo, allowed a significant increase in BMD within 2 years in all anatomical areas. In the lumbar zone, an increase in BMD was noted 1 month after the introduction of the first dose and persisted during therapy, regardless of the duration of treatment with an aromatase inhibitor, the patient's age, BMI, previous use of the selective estrogen receptor modulator (SERM) and chemotherapy, as well as the period since the onset of menopause. …

Pharmacokinetics

For denosumab with subcutaneous administration, a dose-dependent non-linear pharmacokinetics in a wide dosage range is characteristic, characterized by an increase in exposure in direct proportion to the dose when it is used from 60 mg (or 1 mg / kg) or more.

After subcutaneous injection of 60 mg of the substance after about 10 days (range 2–28 days), bioavailability was 61%, and the maximum concentration (Cmax) averaged 6 μg / ml (range 1–17 μg / ml). Upon reaching Cmax, the serum level of the substance decreased with an elimination half-life (T _½) of about 26 days (range 6–52 days) and thereafter for 3 months (range 1.5–4.5 months). Six months after the last SC administration, denosumab was not detected in blood serum in 53% of patients.

Against the background of repeated administration of 60 mg denosumab every 6 months, no changes in its pharmacokinetic parameters and cumulation were observed.

Denosumab, like normal immunoglobulin, contains only carbohydrates and amino acids. According to the data obtained in preclinical studies, it is assumed that the biotransformation of the active substance and its subsequent excretion will be carried out by the usual way of clearance and excretion of immunoglobulins from the body, which will lead to breakdown into individual amino acids and small peptide chains.

No racial dependence of the pharmacokinetics of denosumab was found.

Indications for use

According to the instructions, Prolia is recommended for the treatment of the following diseases / conditions:

• postmenopausal osteoporosis;
• loss of bone mass in women with breast cancer using aromatase inhibitors and in men with prostate cancer receiving hormone deprivation therapy.

Contraindications

• hypocalcemia;
• hypersensitivity to any of the constituents of Prolia.

Instructions for use of Prolia: method and dosage

Prolia is administered sc. The drug should be injected on its own only after preliminary instructions from the attending physician or nurse on the technique of performing subcutaneous injection of the solution.

The recommended dose of Prolia is 60 mg administered subcutaneously every 6 months. During the course of therapy, it is advisable to take additional vitamin D and medications containing calcium.

Before carrying out the procedure, it is necessary to make sure that there are no visible inclusions in the solution, as well as evaluate it for color change (only a clear, colorless or pale yellow solution can be used). Do not use PZSh after the last day of the final month of storage indicated on the package.

If the PZSh has a safety device for the needle (safety device), which reduces the risk of a possible accidental prick, this device is automatically activated immediately after the injection to close the needle. You should not try to disassemble the PZSh or activate the protective fuse. If the cap is missing or the needle guard is activated, the syringe cannot be used.

For self-injection, you need to take a new PZS Prolia and tampons soaked in alcohol, alcohol wipes or similar materials. Before the introduction, the PZH should be removed from the refrigerator without holding it by the piston or protective cap, as this may damage the device. You do not need to shake the syringe and remove the needle cap before starting the injection. In order to prevent discomfort at the injection site, before injecting the PZH solution, leave it at room temperature for some time without heating it in any other way (for example, under the influence of direct sunlight, in a microwave oven, in hot water, etc.).

The procedure should be carried out in a well-lit, comfortable area with a clean surface available on which to place all the necessary materials.

The injection is best done in the upper thighs or abdomen. If someone else is administering the solution, you can also use the back of your hands to inject. In the event that the selected area of the skin for the injection is reddened or swollen, it is recommended to inject Prolia elsewhere.

With thoroughly washed hands, you should disinfect the selected injection site with a swab soaked in alcohol. To prevent the needle from bending, it is necessary to carefully remove the protective cap from it by pulling it up without twisting, without pressing the plunger or touching the needle. If there are small air bubbles inside the syringe, there is no need to remove the latter, since a solution with small air bubbles is suitable for injection.

Pressing the skin (but not squeezing it) between the thumb and forefinger, insert the needle at a 45 ° angle into the base of the fold to about 15 mm. While continuing to hold the skin clamped, you need to gently and slowly press on the piston, pushing it until the solution is injected in full. The needle protector will only work if the PZSh becomes empty.

Without decreasing the pressure on the piston, it is necessary to remove the needle from the skin and release the skin fold, and then, stopping the pressure on the piston, allow the safety guard to cover the entire needle. Failure to activate the safety device may indicate an incomplete dose of Prolia, which requires consultation with your doctor.

The cap should not be installed on a used syringe. If blood comes out at the point of the injection puncture, it must be carefully removed with a gauze cloth or cotton swab, without rubbing the skin. If necessary, you can seal the injection site with a plaster.

One PZH is intended for the administration of one dose only, the remaining solution in the syringe must not be used. The used syringe must be disposed of in accordance with the rules recommended by the pharmacist or attending physician.

Side effects

• metabolism and electrolyte metabolism: extremely rare - hypocalcemia;
• the musculoskeletal system and connective tissue: often - pain in the limbs, rarely - osteonecrosis of the jaw;
• organ of vision: often - cataracts in men with prostate cancer who are on androgen deprivation therapy;
• infections and invasions: infrequently - inflammation of the subcutaneous tissue;
• skin and subcutaneous fat: infrequently - eczema (including dermatitis - atopic, allergic and contact).

Overdose

Overdose cases of Prolia during clinical studies with the introduction of denosumab at a dose of up to 180 mg every 4 weeks (for 6 months the cumulative dose was less than 1080 mg) were not recorded.

special instructions

Before starting treatment with denosumab with existing hypocalcemia, its correction can be carried out with the use of vitamin D and calcium preparations. Patients prone to hypocalcemia should be monitored for calcium levels.

During the treatment of Prolia, infections of the skin and its appendages are sometimes observed (especially inflammatory processes in the subcutaneous tissue), which in some cases may lead to the need for hospitalization. In the course of studies, the development of such reactions was recorded mainly in the group using denosumab (0.4%) when compared with the group using placebo (0.1%). The overall incidence of skin infections was comparable in both study groups. If you experience symptoms of inflammation of the subcutaneous tissue, you should urgently consult a doctor.

There have been reports of the development of osteonecrosis of the jaw in patients with advanced cancer who took 120 mg of denosumab every 4 weeks. There have also been isolated reports of this complication when using denosumab 60 mg every 6 months.

Patients who are allergic to latex should avoid touching the rubber needle cap (a latex derivative).

Influence on the ability to drive vehicles and complex mechanisms

The influence of Prolia on the ability to control complex mechanisms, including motor vehicles, has not been studied.

Application during pregnancy and lactation

It is not recommended to use Prolia during pregnancy, since there are no data on its use during this period.

According to the results of toxicological studies of denosumab in lower primates, the drug, administered in doses 100 times higher than those recommended for use in humans, did not have a negative effect on fetal development and fertility.

In experiments on mice with a gene turned off, it was demonstrated that the absence of RANKL can cause the development of lymph nodes in the fetus, in addition, there is a possibility of weakening lactation, due to a possible effect on the maturation of the mammary gland. Also, according to experimental studies, inhibition of the RANK / RANKL interaction in combination with the binding of osteoprotegerin to the Fc-fragment (OPG-Fc) caused a slowdown in bone growth and impaired dentition. As a result, against the background of the use of Prolia in children, it is possible to inhibit the growth of bones with open growth zones and disrupt the process of teething.

It is not known whether denosumab penetrates into breast milk, but since the drug can cause negative effects in infants, if it is necessary to use it during lactation, breastfeeding should be stopped.

Pediatric use

The pharmacokinetics of denosumab in patients under the age of 18 has not been studied.

Prolia is not recommended for use in pediatric practice, since there is no information confirming its safety and effectiveness in children and adolescents.

With impaired renal function

When conducting studies with the participation of 55 patients who had various stages of renal failure, including in patients requiring dialysis, no effect of the severity of renal pathologies on the pharmacodynamics and pharmacokinetics of denosumab was found. In connection with the above, this category of patients does not need to adjust the dosage regimen.

In patients on dialysis, patients with severe renal failure (creatinine clearance less than 30 ml / min), the threat of hypocalcemia is aggravated by the use of Prolia. They are advised to take additional calcium and vitamin D supplements.

For violations of liver function

The safety profile of denosumab in patients with liver pathologies has not been studied.

Use in the elderly

No significant effect of age on the pharmacokinetic parameters of denosumab when used in patients aged 28–87 years was found.

Patients over 65 years of age do not need to correct the Prolia dosage regimen.

Drug interactions

Drug interaction studies of denosumab with other substances / drugs have not been conducted.

Prolia is not recommended to be mixed with other drugs.

Analogs

Exjiva is an analogue of Prolia.

Terms and conditions of storage

Store out of the reach of children, at a temperature of 2-8 ° C, without freezing, in the original packaging (to protect from light).

Once removed from the refrigerator at a temperature not exceeding 25 ° C, the solution can be stored in its original packaging for a maximum of 30 days.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Prolia

There are very few reviews of Prolia, and they are quite contradictory. According to some reviews, patients who received only 1 injection of the drug, 6 months after the injection, noted an improvement in their condition, confirmed by the result of another densitometry. All reviews pointed out the inadmissibility of self-medication with the drug and the need to strictly follow all the doctor's prescriptions.

According to other patients, Prolia did not help them at all or its effectiveness was negligible. The disadvantages of the tool, almost all patients attribute its high cost. There are no data on side effects.

Price for Prolia in pharmacies

The price of Prolia can be approximately: a solution in a syringe containing 1 ml / 60 mg, with a needle protection device - 15350-16900 rubles.

Prolia: prices in online pharmacies

Drug name Price Pharmacy

Prolia 60 mg / ml solution for subcutaneous administration 1 ml 1 pc. 12336 RUB Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!