Drug Information

Indication:

BRIEF SUMMARY

ROMOSOZUMAB-( Apr- 2019)

Indn- To treat osteoporosis at high risk of fracture

Comp- Injection: 105 mg/1.17 mL solution in a single-use prefilled syringe. A full dose requires two single-use prefilled syringes. • Two separate subcutaneous injections are needed to administer the total dose of 210 mg. Inject two syringes, one after the other. • Should be administered by a healthcare provider.

ADR- The most common adverse reactions (= 5%) reported with EVENITY in clinical trials were arthralgia and headache.

Ci- • Hypocalcemia

WARNINGS-

• Major Adverse Cardiac Events (MACE): Monitor for symptoms of MI and stroke and seek prompt medical attention if symptoms occur. • Hypersensitivity: Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticaria. Discontinueif a clinically significant allergic reaction occurs.

Pat Inform-

Hypersensitivity Reactions-Advise patients to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction including angioedema, erythema multiforme, dermatitis, rash, and urticaria.

Calcium and Vitamin D Supplements to Prevent Hypocalcemia-Advise patients to take calcium and vitamin D supplements daily to reduce the risk of hypocalcemia. Advise patients to seek immediate medical attention for symptoms of hypocalcemia

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U.S. FDA APPROVED DRUGS DURING 2019

Sr.No-7

Name of the Drug- EVENITY

Active Ingredient - Romosozumab-aqqg

Pharmacological Classification-

To treat osteoporosis at high risk of fracture

Date of Approval - 4/9/2019

(Ref- FDA approved List 2019 )

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

EVENITY safely and effectively. See full prescribing information for EVENITY. EVENITY™ (romosozumab-aqqg) injection, for subcutaneous use

Initial U.S. Approval: 2019

WARNING: POTENTIAL RISK OF MYOCARDIAL INFARCTION, STROKE AND CARDIOVASCULAR DEATH See full prescribing information for complete boxed warning.

• EVENITY may increase the risk of myocardial infarction, stroke and cardiovascular death.

• EVENITY should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors.

• If a patient experiences a myocardial infarction or stroke during therapy, EVENITY should be discontinued.

INDICATIONS AND USAGE

- EVENITY is a sclerostin inhibitor indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.

Limitations of Use: Limit duration of use to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered.

Adverse Reaction:

ADVERSE REACTIONS

The most common adverse reactions (= 5%) reported with EVENITY in clinical trials were arthralgia and headache.

Contra-Indications:

CONTRAINDICATIONS

• Hypocalcemia

• Known hypersensitivity to EVENITY

WARNINGS AND PRECAUTIONS

• Major Adverse Cardiac Events (MACE): Monitor for symptoms of MI and stroke and seek prompt medical attention if symptoms occur.

• Hypersensitivity: Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticaria. Discontinue EVENITY if a clinically significant allergic reaction occurs.

• Hypocalcemia: Adequately supplement calcium and vitamin D during treatment with EVENITY.

• Osteonecrosis of the Jaw: Monitor for symptoms. Consider discontinuation of therapy based on benefit-risk assessment.

• Atypical Femoral Fracture: Evaluate new or unusual thigh, hip, or groin pain to rule out an incomplete femur fracture.

Dosages/ Overdosage Etc:

WARNING: POTENTIAL RISK OF MYOCARDIAL INFARCTION, STROKE AND CARDIOVASCULAR DEATH See full prescribing information for complete boxed warning.

• EVENITY may increase the risk of myocardial infarction, stroke and cardiovascular death.

• EVENITY should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors.

• If a patient experiences a myocardial infarction or stroke during therapy, EVENITY should be discontinued.

INDICATIONS AND USAGE

- EVENITY is a sclerostin inhibitor indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.

Limitations of Use: Limit duration of use to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered.

DOSAGE AND ADMINISTRATION

• Two separate subcutaneous injections are needed to administer the total dose of 210 mg. Inject two syringes, one after the other.

• Should be administered by a healthcare provider.

• Administer 210 mg subcutaneously once every month for 12 doses in the abdomen, thigh, or upper arm.

• Adequately supplement calcium and vitamin D during treatment.

DOSAGE FORMS AND STRENGTHS

Injection: 105 mg/1.17 mL solution in a single-use prefilled syringe. A full dose of EVENITY requires two single-use prefilled syringes.

Patient Information:

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Major Adverse Cardiac Events

Advise patients to seek immediate medical attention if they experience signs or symptoms of a myocardial infarction or stroke.

Hypersensitivity Reactions

Advise patients to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction including angioedema, erythema multiforme, dermatitis, rash, and urticaria

Calcium and Vitamin D Supplements to Prevent Hypocalcemia

Advise patients to take calcium and vitamin D supplements daily to reduce the risk of hypocalcemia. Advise patients to seek immediate medical attention for symptoms of hypocalcemia

Osteonecrosis of the Jaw

Advise patients to practice good oral hygiene during treatment with EVENITY and tell their dentist that they are receiving EVENITY before having dental work.

Atypical Femoral Fracture

Advise patients to report signs and symptoms that could be consistent with impending atypical femoral fracture including new or unusual thigh, hip, or groin pain

EVENITY™ (romosozumab-aqqg)

Pharmacology/ Pharmacokinetics:

CLINICAL PHARMACOLOGY

1. Mechanism of Action

EVENITY inhibits the action of sclerostin, a regulatory factor in bone metabolism. EVENITY increases bone formation and, to a lesser extent, decreases bone resorption.

Animal studies showed that romosozumab-aqqg stimulates new bone formation on trabecular and cortical bone surfaces by stimulating osteoblastic activity resulting in increases in trabecular and cortical bone mass and improvements in bone structure and strength

2. Pharmacodynamics In postmenopausal women with osteoporosis, EVENITY increased the bone formation marker procollagen type 1 N-telopeptide (P1NP) with a peak increase from baseline of approximately 145% compared to placebo 2 weeks after initiating treatment, followed by a return to concentrations seen with placebo at month 9 and a decline from baseline to approximately 15% below the concentration change seen with placebo at month

2. Pharmacokinetics

Administration of a single dose of 210 mg EVENITY in healthy volunteers resulted in a mean (standard deviation [SD]) maximum romosozumab-aqqg serum concentration (Cmax) of 22.2 (5.8) mcg/mL and a mean (SD) AUC of 389 (127) mcg*day/mL.

Steady-state concentrations were achieved by month 3 following the monthly administration of 210 mg to postmenopausal women.

Absorption

The median time to maximum romosozumab-aqqg concentration (Tmax) is 5 days (range: 2 to 7 days).

Distribution

The estimated volume of distribution at steady-state is approximately 3.92 L.

Elimination

Romosozumab-aqqg exhibited nonlinear pharmacokinetics with the clearance of romosozumab-aqqg decreasing as the dose increased. The estimated mean systemic clearance (CL/F) of romosozumab-aqqg was 0.38 mL/hr/kg, following a single subcutaneous administration of 3 mg/kg (the approved recommended dosage for a 70 kg woman).

The mean effective t1/2 was 12.8 days after 3 doses of 3 mg/kg (the approved recommended dosage for a 70 kg woman) every 4 weeks.

Metabolism

The metabolic pathway of romosozumab-aqqg has not been characterized. As a humanized IgG2 monoclonal antibody, romosozumab-aqqg is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

EVENITY is not indicated for use in women of reproductive potential.

In animal reproduction studies, weekly administration of romosozumab-aqqg to pregnant rats during the period of organogenesis at exposures greater than 32 times the clinical exposure produced skeletal abnormalities in the offspring.

2. Lactation Risk Summary

EVENITY is not indicated for use in women of reproductive potential.

3.Pediatric Use

Safety and effectiveness of EVENITY have not been established in pediatric patients

4. Geriatric Use

Of the 6544 postmenopausal women with osteoporosis in the clinical studies of EVENITY, 5234 (80%) were age 65 years and over and 2390 (37%) were age 75 years and over.

No overall differences in safety or efficacy were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

5.Renal Impairment

No dose adjustment is required in patients with renal impairment.

Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m2 by MDRD equation) or receiving dialysis are at greater risk of developing hypocalcemia

Monitor calcium concentrations and adequately supplement calcium and vitamin D in patients who have severe renal impairment or are receiving dialysis.

7/19. Romosozumab-aqqg- (EVENITY) @ (Apr-2019)- Anti-arthritic

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Pregnancy and lactation