EVENITY^® (romosozumab)
Prescriber Guide

This guide contains important safety information for Healthcare
Professionals to minimise key risks when prescribing romosozumab.

Start Prescriber GuideLength: 8 minutes

In the resources section, you can download the SmPC and the Prescriber Guide (in your selected language)
as well as the Patient Alert Card (in your patient’s selected language).

The patient or, if appropriate, their caregiver should be educated about treatment risks and provided with
a Patient Alert Card.

See Summary of Product Characteristics (SmPC) for full prescribing information (For Europe)

See Summary of Product Characteristics (SmPC) for full prescribing information (For Switzerland)

EVENITY (romosozumab) is indicated in treatment of severe osteoporosis in postmenopausal women at high risk of fracture.¹

About
romosozumab

Key Risks

Managing
Key Risks

Checklist

Patient
Alert Card

Summary

About Romosozumab

Administer 12 once-monthly doses then transistion to antiresorptive therapy

Transition to antiresorptive therapy is recommended in order to extend the benefit achieved with
romosuzumab beyond 12 months

Two pre-filled pens 12 months Transition

About Romosozumab

To administer the 210 mg dose, 2 subcutaneous injections of romosozumab should be given into the abdomen, thigh, or upper arm. The second injection should be given immediately after the first one but at a different injection site.

Patients should be adequately supplemented with calcium and vitamin D before and during treatment.

Patients treated with EVENITY should be given the package leaflet and the patient alert card.

Romosozumab administration should be performed by an individual who has been trained in injection techniques.
Information on how to inject romosozumab is provided in the ‘Instructions for Use’ section of the package leaflet.

About Romosozumab

EVENITY (romosozumab) is a humanised monoclonal antibody that binds and inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption.

EVENITY (romosozumab) is indicated in treatment of severe osteoporosis in postmenopausal women at high risk of fracture.

EVENITY is contraindicated in patients with hypersensitivity, hypocalcaemia and history of myocardial infarction or stroke.

Key Risks

Risk of Hypocalcaemia, Mycocardial Infarction (MI) and Osteonecrosis of the Jaw (ONJ) associated with romosozumab use

Romosozumab is contraindicated in patients with hypocalcaemia. Patients should have their serum calcium levels measured before initiating romosozumab therapy and should be monitored for signs and symptoms of hypocalcaemia throughout treatment.

Romosozumab is contraindicated in patients with history of MI or stroke. In patients without history of MI or stroke, the individual benefit-risk balance of using romosozumab treatment should be carefully evaluated prior to prescribing.

Risk factors for the development of ONJ should be considered and preventative measures encouraged prior to prescribing romosozumab.

Patients should be educated about these risks.

The next section provides further information on how to manage the risks associated with EVENITY (romosozumab) use.
For detailed information about these and other risks, please refer to the SmPC.

Managing Key Risks

Osteonecrosis of the jaw

ONJ is a rare side effect of antiresorptive drugs. It is defined as exposed bone, or bone that can be probed through an intra-oral or extra-oral fistula, in the maxillofacial region, that has persisted for more than eight weeks in patients with a history of treatment with antiresorptive or anti-angiogenic drugs, and where there has been no history of radiation therapy to the jaws or obvious metastatic disease to the jaws.¹

ONJ has been reported rarely (≥ 1/10,000 to < 1/1,000) in patients receiving romosozumab.

Managing Key Risks

Osteonecrosis of the jaw - Staging and treatment strategies

ONJ Stage 3
Exposed and necrotic bone, or a fistula that probes to bone, in patients with pain, infection, and one or more of the following: exposed and necrotic bone extending beyond the region of alveolar bone* resulting in pathologic fracture, extra-oral fistula, oral antral/oral nasal communication, or osteolysis extending to the inferior border of the mandible of sinus floor.

Treatment

Antibacterial mouth rinse.
Antibiotic therapy and pain control.
Surgical debridement/resection for longer-term palliation of infection and pain.

*Inferior border and ramus in the mandible, maxillary sinus and zygoma in the maxilla.

Discontinuation of romosozumab therapy should be considered until the condition resolves and contributing risk factors are mitigated where possible.

Managing Key Risks

Osteonecrosis of the jaw - Staging and treatment strategies

ONJ Stage 2
Exposed and necrotic bone, or a fistula that probes to bone, associated with infection as evidenced by pain and erythema in the region of the exposed bone with or without purulent drainage.

Treatment

Symptomatic treatment with oral antibiotics.
Oral antibacterial mouth rinse.
Pain control.
Debridement to relieve soft tissue irritation and infection control.

Managing Key Risks

Osteonecrosis of the jaw - Staging and treatment strategies

ONJ Stage 0
No clinical evidence of necrotic bone, but non-specific clinical findings, radiographic changes and symptoms.

Treatment

Systemic management, including the use of pain medication and antibiotics.

ONJ Stage 1
Exposed and necrotic bone, or a fistula that probes to bone, in patients who are asymptomatic and have no evidence of infection.

Treatment

Antibacterial mouth rinse.
Clinical follow-up on a quarterly basis.
Patient education and review of indications for continued bisphosphonate therapy.

Managing Key Risks

Osteonecrosis of the jaw - Risk factors

The following risk factors should be considered when evaluating a patient’s risk of developing ONJ:

Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive dental procedures, e.g. tooth extractions.

Potency of the medicinal product that inhibits bone resorption (the risk increases with the anti-resorptive potency of the compound), and cumulative dose of antiresorptive therapy.

Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking.

Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to the head and neck.

Managing Key Risks

Osteonecrosis of the jaw - Management

All patients should be encouraged to:

Immediately report any oral symptoms, such as pain or swelling or non-healing of sores or discharge during treatment with romosozumab.

Maintain good oral hygiene.

Receive routine dental check-ups.

If appropriate, consider arranging a dental examination before a patient starts romosozumab treatment.

Patients who are suspected of having or who develop ONJ while on romosozumab should receive care by a dentist or an oral surgeon with expertise in ONJ. Discontinuation of romosozumab therapy should be considered until the condition resolves and contributing risk factors are mitigated where possible.

Managing Key Risks

Myocardial infarction and stroke - Background

In two large, controlled fracture trials of romosozumab for the treatment of osteoporosis in postmenopausal women, serious cardiovascular adverse events were prospectively adjudicated.

In the active-controlled trial (n=4,054) during the 12-month double-blind treatment phase:

16 women (0.8%) had myocardial infarction in the romosozumab arm versus 5 women (0.2%) in the alendronate arm.

13 women (0.6%) had stroke in the romosozumab arm versus 7 women (0.3%) in the alendronate arm.

In the placebo-controlled trial (n=7,157), no imbalance was observed during the 12-month double-blind treatment phase.

Managing Key Risks

Myocardial infarction and stroke - Management

Patients without history of MI or stroke:
When determining whether to use romosozumab for an individual patient, consideration should be given to her fracture risk over the next year and her cardiovascular risk based on risk factors (e.g. established cardiovascular disease, hypertension, hyperlipidaemia, diabetes mellitus, smoking, severe renal impairment, age). Romosozumab should only be used if the benefit outweighs the risk.

Patients who develop symptoms suggestive of MI or stroke during romosozumab treatment should undergo a prompt medical evaluation. If a patient experiences a myocardial infarction or stroke during therapy, treatment with romosozumab should be discontinued.

Managing Key Risks

Myocardial infarction and stroke - Management

In randomised controlled studies, an increase in serious cardiovascular events (myocardial infarction and stroke) has been observed in romosozumab treated patients compared to controls.

Patients with history of MI or stroke:
Romosozumab is contraindicated and should not be initiated.

Managing Key Risks

Hypocalcaemia - Patients with severe renal impairment or
undergoing dialysis

Patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m²) or receiving dialysis are at greater risk of developing hypocalcaemia and the safety data for these patients is limited.

Calcium levels should be monitored in these patients.

Managing Key Risks

Hypocalcaemia - Management

Monitor patients for signs and symptoms of hypocalcaemia throughout treatment.

The predominant features of hypocalcaemia are effects on the nerves and muscles and may include:

Muscle cramps and/or spasms

Paraesthesia of the extremities or periorally

Seizures

Facial twitches

Neuropsychiatric effects, ranging from confusion and disorientation to overt psychosis

Managing Key Risks

Hypocalcaemia - Management

Transient hypocalcaemia was observed in patients receiving romosozumab in clinical trials.

Hypocalcaemia is a contraindication. Correct hypocalcaemia prior to initiating therapy with romosozumab.

Patients should be adequately supplemented with calcium and vitamin D prior to and during romosozumab treatment.

If any patient presents with suspected signs and/or symptoms of hypocalcaemia during treatment, serum calcium levels should be measured. Signs and symptoms are listed on the next screen.

Checklist

General Reminder List

Before prescribing romosozumab, you should ensure:

Serum calcium levels are measured prior to treatment initiation, and hypocalcaemia is corrected before administering romosozumab
Patients are adequately supplemented with calcium and vitamin D before and during treatment, as appropriate
Serum calcium levels are monitored for patients with severe renal impairment or receiving dialysis, who are at increased risk of developing hypocalcaemia
The benefit of using romosozumab outweighs the risk
Patients have been provided with the Patient Alert Card and read the package leaflet
Patients and/or their caregivers are trained on subcutaneous injection technique if they will administer romosozumab, including the Instructions for Use described in the package leaflet

Risk factors for developing osteonecrosis of the jaw are considered, including:
- Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive dental procedures, e.g. tooth extractions
- Potency of the medicinal product that inhibits bone resorption, and cumulative dose of antiresorptive therapy
- Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking
- Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to the head and neck

Checklist

Risk of Myocardial Infarction and Stroke

Before prescribing romosozumab, you should:

Verify that patients do not have a history of myocardial infarction or stroke, which is a contraindication
Ensure that the benefit of using romosozumab outweighs the risk

Perform a careful assessment of the cardiovascular risk profile
- Consider risk factors such as established cardiovascular disease, hypertension, hyperlipidaemia, diabetes mellitus, smoking, severe renal impairment, and age

Patient Alert Card

Patients or, if appropriate, their caregiver should be educated to reinforce understanding of these risks and the importance of contacting a healthcare professional if they experience suggestive signs and/or symptoms.

A Patient Alert Card should be provided to each patient prescribed romosozumab. This card aids patients in remembering or recognising signs and symptoms of key risks that are associated with romosozumab treatment.

It also provides guidance to patients on what they should do should they experience signs and/or symptoms.

Patient Alert Card

Patients should be advised to carry the Patient Alert Card with them at all times and to show it to any Healthcare Professional who may be treating them.

Patient Alert Card

Select and download a Patient Alert Card in your desired language

EVENITY® (romosozumab)Prescriber Guide

See Summary of Product Characteristics (SmPC) for full prescribing information (For Europe)

See Summary of Product Characteristics (SmPC) for full prescribing information (For Switzerland)

EVENITY (romosozumab) is indicated in treatment of severe osteoporosis in postmenopausal women at high risk of fracture.1

About romosozumab

Key Risks

Managing Key Risks

Checklist

Patient Alert Card

Summary

Administer 12 once-monthly doses then transistion to antiresorptive therapy

Romosozumab administration should be performed by an individual who has been trained in injection techniques. Information on how to inject romosozumab is provided in the ‘Instructions for Use’ section of the package leaflet.

EVENITY (romosozumab) is a humanised monoclonal antibody that binds and inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption.

Risk of Hypocalcaemia, Mycocardial Infarction (MI) and Osteonecrosis of the Jaw (ONJ) associated with romosozumab use

Osteonecrosis of the jaw

Osteonecrosis of the jaw - Staging and treatment strategies

Osteonecrosis of the jaw - Staging and treatment strategies

Osteonecrosis of the jaw - Staging and treatment strategies

Osteonecrosis of the jaw - Risk factors

Osteonecrosis of the jaw - Management

Myocardial infarction and stroke - Background

Myocardial infarction and stroke - Management

Myocardial infarction and stroke - Management

Hypocalcaemia - Patients with severe renal impairment or undergoing dialysis

Hypocalcaemia - Management

Hypocalcaemia - Management

General Reminder List Before prescribing romosozumab, you should ensure:

Risk of Myocardial Infarction and Stroke Before prescribing romosozumab, you should:

Patient Alert Card

Patient Alert Card

Resources

EVENITY^® (romosozumab)
Prescriber Guide

EVENITY (romosozumab) is indicated in treatment of severe osteoporosis in postmenopausal women at high risk of fracture.¹

About
romosozumab

Managing
Key Risks

Patient
Alert Card

Romosozumab administration should be performed by an individual who has been trained in injection techniques.
Information on how to inject romosozumab is provided in the ‘Instructions for Use’ section of the package leaflet.

Hypocalcaemia - Patients with severe renal impairment or
undergoing dialysis

General Reminder List

Before prescribing romosozumab, you should ensure:

Risk of Myocardial Infarction and Stroke

Before prescribing romosozumab, you should: