Romosozumab (Evenity) is administered as a monthly injection for the treatment of patients with osteoporosis. It is a humanized monoclonal IgG directed against sclerostin that is one of the primary factors responsible for bone metabolism. Unlike bisphosphonates (alendronate, zoledronic acid, pamidronic acid), it can be given in patients with renal impairment. Denosumab (Prolia) is another drug that can be given in patients with renal impairment.

Romosozumab (Evenity) Uses:

• Osteoporosis:

  • It is indicated for the treatment of osteoporosis in women of postmenopausal age groups who are at high risk for fracture or those patients who have failed or are intolerant to other available therapies of osteoporosis.
  • A high fracture risk group is defined as a patient with a history of osteoporotic fracture or those with multiple risk factors for fracture.
• Limitations of use:
  • The anabolic effects of the drug wane after twelve doses administered monthly (or after one year of the treatment)
  • Therefore, the treatment duration must not exceed one year.
  • Patients who require continued treatment for osteoporosis, other anti-resorptive therapies may be considered.

Romosozumab (Evenity) Dose in Adults

Note:

• The drug must be administered with supplemental calcium and vitamin D.
• The usual dose for calcium and vitamin D that has been studied in clinical trials is a daily dose of 500 mg to 1000 mg calcium and 600 to 800 units per day of vitamin D.

Romosozumab (Evenity) Dose in the treatment of Osteoporosis in postmenopausal females:

• It is administered as two consecutive SubQ injections 105 mg each (total dose of 210 mg) once a month.
• The treatment is continued for a total of twelve months.
• Note:
  • After discontinuation, the marker of bone resorption (type 1 collagen C-telopeptide) increase and return to above baseline levels within three months.
  • Within twelve months, the bone mineral density (BMD) returns to the baseline.
  • Patients who need osteoporosis treatment following the discontinuation of romosozumab, treatment with anti-resorptive therapy may be considered.

• Missed dose:

  • In case, a dose is missed, it should be administered immediately. The next dose should be scheduled from the date of the last dose administered.

Use in Children:

It is not indicated for use in children.

Romosozumab (Evenity) Pregnancy Risk Category: N (Not assigned)

• It is a monoclonal humanized monoclonal antibody, of the IgG subtype.
• This means that it crosses the placental boundary, especially in the third trimester. The drug's placental transfer is very limited during organogenesis.
• Romosozumab should not be used in the treatment of osteoporosis in women of reproductive age.

Romosozumab use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• For osteoporosis treatment in women of reproductive age, evenity is not recommended.

Romosozumab (Evenity) Dose in Kidney Disease:

• Adjustment in the dose is not necessary in patients with renal impairment.
• All patients with eGFR <30 mL/minute/1.73 m² or those patients who are on dialysis should be monitored for hypocalcemia at regular intervals.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Common Side Effects of Romosozumab (Evenity):

• Neuromuscular & skeletal:

  • Arthralgia

Less Common Side Effects of Romosozumab (Evenity):

• Cardiovascular:

  • Cardiac Disorder
  • Peripheral Edema

• Central Nervous System:

  • Headache
  • Insomnia
  • Paresthesia

• Dermatologic:

  • Skin Rash

• Hypersensitivity:

  • Hypersensitivity Reaction

• Local:

  • Injection Site Reaction
  • Pain At Injection Site
  • Erythema At Injection Site

• Neuromuscular & Skeletal:

  • Muscle Spasm
  • Asthenia
  • Neck Pain

Contraindication to Romosozumab (Evenity):

• Allergy reactions to romosozumab and any component of the formulation. 
• Angioedema or erythema multiforme may be symptoms of allergic reactions.
• Hypocalcemia uncorrected

Warnings and precautions

• Bone fractures:

  • Patients receiving romosozumab therapy have reported femur fractures along their femoral shafts. These fractures can be bilateral or occur with minimal trauma.
  • Patients may experience pain for several weeks before they feel the need to have a fracture.
  • Patients who have romosozumab treatment and experience unusual hip, thigh or groin pains should be considered for atypical Femur fractures. These symptoms should be evaluated to rule out a partial femoral injury.
  • Patients with a femoral injury on one side of the body should also have their contralateral limbs evaluated.
  • These patients may have their treatment interrupted.

• Cardiovascular events: [US Boxed Warn]

  • Patients who have suffered a stroke or myocardial damage in the last year should not receive Romosozumab treatment. It has been linked to an increased risk of stroke, myocardial injury, and cardiovascular death.
  • Patients at high risk for developing cardiovascular disease should weigh the risks and benefits of treatment.
  • Patients who have suffered any type of cardiovascular event during therapy may have to stop receiving the treatment.

• Hypocalcemia:

  • Patients with uncorrected hypocalcemia are not advised to receive treatment.
  • To avoid hypocalcemia, patients should be given adequate vitamin D and calcium supplementation prior to and during treatment.
  • Patients at high risk for developing hypocalcemia, such as dialysis patients or those with renal impairment, should have their serum calcium levels closely monitored.

• Hypersensitivity

  • Angioedema, erythema multifle, urticaria and rash can all be caused by allergic reactions.
  • If patients experience severe allergic reactions, such as anaphylaxis, the treatment might need to be stopped.

• Osteonecrosis in the jaw:

  • With romosozumab therapy, it has been reported that medication-related osteonecrosis (MRONJ), or simply osteonecrosis (ONJ), can occur in the jaw.
  • MRONJ is a serious condition that can be fatal to patients who are:
    • Patients who recently had to have their teeth extracted or have undergone other invasive dental procedures.
    • Cancer diagnosis
    • Radiotherapy is performed on patients
    • Concomitant treatment using angiogenesis inhibitors or bisphosphonates, chemotherapy and corticosteroids or denosumab.
    • People with poor oral hygiene are at greater risk of developing a serious health problem.
    • Patients with comorbid conditions such as anemia or coagulopathy, infection, preexisting periodontal disease, or other periodontal problems.
  • Before any treatment, all patients should have a routine oral exam. Patients should also be instructed to practice good oral hygiene.
  • Patients who require invasive dental treatment should weigh the risks and benefits.
  • A dentist or an oral surgeon should evaluate patients who have MRONJ. These patients may have to stop receiving treatment.

Monitoring parameters:

Monitor for signs and symptoms of hypersensitivity, serum calcium, and the clinical features of adverse cardiovascular events.

Osteoporosis recommendations:

• Evaluate bone mineral density every one to three years while on treatment for osteoporosis.
• The maximum duration of romosozumab treatment is one year. After the treatment is discontinued, bone mineral density decreases to baseline within one year.
• The markers of bone turnover may be monitored at baseline and every three to six months. These include P1NP (Procollagen type 1 N-telopeptide), a marker of bone formation, and CTX (type 1 collagen C-telopeptide), a marker of bone resorption.
• It is important to take samples for the markers of bone turnover in the fasting state early in the morning as the effect of food and diurnal variations may alter the results.

How to administer Romosozumab (Evenity)?

• It is administered as two consecutive subQ injections administered each month.
• When administering the dose, two syringes should be removed from the carton and allowed at room temperature for at least thirty minutes before administration.
• The injection should be administered sub Q into the abdomen, thigh, or outer area of the upper arm. The injection sites must be rotated.
• If the dose is to be administered into the same area, it should not be injected into the same spot.
• It should not be injected into infected, tender, red, hard, or erythematous areas. Injection into sites that are scarred or bruised should be avoided too.
• Prior to injecting, inspect the solution in the syringe. It should appear clear to opalescent, colorless to light yellow. Do not use if the solution is cloudy, discolored, or contains particulate matter.

Mechanism of action of Romosozumab (Evenity):

• Romosozumab is a drug that increases bone formation.
• To a lesser degree, it decreases bone loss by inhibiting sclerostin.
• Sclerostin regulates bone metabolism and inhibits the Wnt/Beta catenin signaling pathway that regulates bone growth.

The beginning of action:

• Procollagen type 1 N telopeptide is a marker for bone formation, while type 1 collagen C telopeptide is a mark of bone resorption.
• Two weeks after treatment begins, the maximum increase in P1NP and the lowest CTX are observed.
• Two months after treatment began, patients notice an increase in their histomorphometric indices for bone formation.

Time of action:

• CTX remains low for twelve months.
• P1NP returns back to baseline in nine months, and falls at twelve months.
• After twelve months of treatment, the anabolic effect fades.
• Within three months of treatment being stopped, CTX levels rise above baseline. 
• Within twelve months, CTX, P1NP and bone mineral density (BMD), return to baseline.

Metabolism:

• It is not known what the metabolic pathways are. It is likely to be degraded via catabolic pathways, just like other endogenous IgG.

Half-life elimination:

• 12.8 days after the administration of three doses over a 12-week period (ie, one dose every month)

Time to peak:

• Median: 5 days (range: 2 to 7 days)

International Brands of Romosozumab:

• Evenity

Romosozumab Brand Names in Pakistan:

No Brands Available in Pakistan.