Prolia 60 mg

/ Amgen

The recommended dose of Prolia is 60 mg administered as a single subcutaneous injection once every 6 months into the thigh, abdomen or upper arm. Patients must be adequately supplemented with calcium and vitamin D.
Patients with renal impairment: No dose adjustment is required in patients with renal impairment.
No data is available in patients with long-term systemic glucocorticoid therapy and severe renal impairment (GFR < 30 mL/min).
Patients with hepatic impairment: The safety and efficacy of denosumab have not been studied in patients with hepatic impairment.
Elderly Patients (age  65): No dose adjustment is required in elderly patients.
Paediatric Population: Prolia is not indicated for use in children and adolescents below 18 years.
See prescribing information for full details.

Treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures. In postmenopausal women Denosumab significantly reduces the risk of vertebral, non -vertebral and hip fractures.
Treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. In men with prostate cancer receiving hormone ablation, Denosumab significantly reduces the risk of vertebral fractures.
Treatment of bone loss associated with long-term systemic glucocorticoid therapy of a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 3 months, in adult patients at high risk of fracture.

Hypersensitivity to the active substance or to any of the excipients.
Hypocalcaemia.

Calcium and Vitamin D supplementation: Adequate intake of calcium and vitamin D is important in all patients.
Precautions for use:
Hypocalcaemia: It is important to identify patients at risk for hypocalcaemia. Hypocalcaemia must be corrected by adequate intake of calcium and vitamin D before initiating therapy. Clinical monitoring of calcium levels is recommended before each dose and, in patients predisposed to hypocalcaemia within two weeks after the initial dose. If any patient presents with suspected symptoms of hypocalcaemia during treatment calcium levels should be measured. Patients should be encouraged to report symptoms indicative of hypocalcaemia. In the post-marketing setting, severe symptomatic hypocalcaemia (resulting in hospitalization, life‑threatening events, and fatal cases) has been reported, with most cases occurring in the first weeks of initiating therapy, but it can occur later.
Concomitant glucocorticoid treatment is an additional risk factor for hypocalcemia.
Renal impairment: Patients with severe renal impairment (creatinine clearance < 30 mL/min) or receiving dialysis are at greater risk of developing hypocalcemia. The risks of developing hypocalcemia and accompanying parathyroid hormone elevations increase with increasing degree of renal impairment. Severe and fatal cases have been reported. Adequate intake of calcium, vitamin D and regular monitoring of calcium is especially important in these patients.
Skin Infections: Patients receiving this drug may develop skin infections (predominantly cellulitis) leading to hospitalization.  Patients should be advised to seek prompt medical attention if they develop signs or symptoms of cellulitis.
Osteonecrosis of the Jaw (ONJ): ONJ has been reported rarely in patients receiving this drug for osteoporosis. The start of treatment/new treatment course should be delayed in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit risk assessment is recommended prior to treatment with denosumab in patients with concomitant risk factors.
Osteonecrosis of the external auditory canal: Osteonecrosis of the external auditory canal has been reported with denosumab. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving denosumab who present with ear symptoms including chronic ear infections. All patients should be encouraged to maintain good oral hygiene, receive routine dental check ups, and immediately report any oral symptoms such as dental mobility, pain or swelling or non-healing of sores or discharge during treatment with denosumab.
Atypical fractures of the femur: Atypical femoral fractures have been reported in patients receiving denosumab. Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur. Specific radiographic findings characterize these events. Discontinuation of denosumab therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient based on an individual benefit-risk assessment. During denosumab treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patients presenting with such symptoms should be evaluated for an incomplete femoral fracture.
Long-term antiresorptive treatment: Long-term antiresorptive treatment (including both denosumab and bisphosphonates) may contribute to an increased risk for adverse outcomes such as osteonecrosis of the jaw and atypical femur fractures due to significant suppression of bone remodeling.
Treatment discontinuation
Following denosumab discontinuation, decrease in bone mineral density (BMD) is expected, leading to an increased risk for fractures. Monitoring of BMD is recommended, and alternative treatment should be considered according to clinical guidelines.
Concomitant treatment with other denosumab-containing medicinal products: Patients being treated with denosumab should not be treated concomitantly with other denosumab‑containing medicinal products (for prevention of skeletal related events in adults with bone metastases from solid tumors).
Hypercalcemia in pediatric patients: This drug should not be used in pediatric patients (age < 18). Serious hypercalcemia has been reported. Some clinical trial cases were complicated by acute renal injury.
Multiple vertebral fractures (MVF) following discontinuation of denosumab:
Cases of multiple vertebral fractures (MVF) have been reported following denosumab discontinuation in patients with osteoporosis that participated in clinical trials and from post-marketing reports.
Consistent with the pharmacological properties of this drug, treatment discontinuation is associated with reversibility of denosumab effects on bone mineral density (BMD) and bone remodeling. In clinical trials, BMD returned to pre-treatment values following Prolia discontinuation; however in some patients BMD declined to below the baseline value before the beginning of Prolia treatment, but it remained, on average, higher than the previously treated placebo group.
See prescribing information for full details.

The most common side effects with Prolia (seen in more than one patient in ten) are musculoskeletal pain and pain in the extremity. Uncommon cases of cellulitis, rare cases of hypocalcemia, hypersensitivity, osteonecrosis of the jaw and atypical femoral fractures have been observed in patients taking Prolia.
See prescribing information for full details.

In an interaction study, Prolia did not affect the pharmacokinetics of midazolam, which is metabolized by cytochrome P450 3A4 (CYP3A4). This indicates that Prolia should not alter the pharmacokinetics of drugs metabolized by CYP3A4. There are no clinical data on the co-administration of denosumab and hormone replacement therapy (oestrogen), however the potential for a pharmacodynamic interaction is considered to be low.
In postmenopausal women with osteoporosis the pharmacokinetics and pharmacodynamics of denosumab were not altered by previous alendronate therapy, based on data from a transition study (alendronate to denosumab).

Pregnancy: There are no or limited amount of data from the use of denosumab in pregnant women. Studies in animals have shown reproductive toxicity.
Prolia is not recommended for use in pregnant women and women of child-bearing potential not using contraception. Women should be advised not to become pregnant during and for at least 5 months after treatment with Prolia. Any effects of Prolia are likely to be greater during the second and third trimesters of pregnancy since monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester.
Breast-feeding: It is unknown whether denosumab is excreted in human milk. In genetically engineered mice in which RANKL has been turned off by gene removal (a “knockout mouse”), studies suggest absence of RANKL during pregnancy may interfere with maturation of the mammary gland leading to impaired lactation post-partum. A decision on whether to abstain from breast-feeding or to abstain from therapy with Prolia should be made, taking into account the benefit of breast-feeding to the newborn/infant and the benefit of Prolia therapy to the woman.
Fertility: No data are available on the effect of denosumab on human fertility. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

There is no experience with overdose in clinical studies. Denosumab has been administered in clinical studies using doses up to 180 mg every 4 weeks (cumulative doses up to 1,080 mg over 6 months), and no additional adverse reactions were observed.

Storage: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the pre-filled syringe in the original outer carton in order to protect from light.
Once removed from the refrigerator, this medicinal product may be stored at room temperature (up to 25°C) for up to 30 days in the original carton. It must be used within this 30 days period.