LCD/NCD Portal

L32100

 

BISPHOSPHONATES (INTRAVENOUS [IV]) AND MONOCLONAL ANTIBODIES IN THE TREATMENT OF OSTEOPOROSIS AND THEIR OTHER INDICATIONS

 

05/01/2012

 

Indications and Limitations of Coverage and/or Medical Necessity

 

Indications

• This LCD addresses “incident to” drugs that are not self-administered for certain patients with osteoporosis.

• The other indications for these drugs are also addressed.

• The World Health Organization (WHO) defines osteoporosis in a postmenopausal woman or a man over the age of 50 as a bone mineral density (BMD) T-score less than or equal to -2.5 at the total hip, femoral neck, or lumbar spine (at least two vertebral levels measured in the posterior-anterior projection, not the lateral projection) as noted below (refer also to LCD for Bone Mineral Density Studies [FL] L29086 and [PR/VI] L29101).

o Normal: T-score above (i.e., better than) or equal to -1.0.

o Osteopenia: T-score between -1.0 and -2.5.

o Osteoporosis: T-score below (i.e., worse than) or equal to -2.5.

• In addition to diagnosis through densitometry, osteoporosis can be diagnosed clinically, regardless of the T-score.

• The presence of a fragility fracture constitutes a clinical diagnosis of osteoporosis.

• It is important to distinguish between risk factors for osteoporosis as defined by BMD and risk factors for osteoporotic fracture.

• The use of BMD T-scores to assess fracture risk can be markedly improved by combining BMD with information about other risk factors, particularly the woman’s age and fracture history.

• The major risk factors in postmenopausal women are advanced age, genetics, lifestyle factors (e.g., low calcium and vitamin D intake, smoking, and heavy alcohol consumption), thinness, and menopausal status.

• Because nearly 50% of postmenopausal women in the community over the age of 50 years who suffer an osteoporotic fracture do not have osteoporosis as defined by a BMD test, the WHO developed the fracture risk assessment tool (FRAX) to identify clinical risk factors of patients at high risk for osteoporotic fractures:

o Age.

o Sex.

o Prior fragility fracture after age 50.

o History of corticosteroid use (5 mg per day or more for three months or longer).

o Parental history of hip fracture.

o Rheumatoid arthritis.

o Secondary osteoporosis (e.g., type 1 diabetes, osteogenesis imperfecta in adults, longstanding hyperthyroidism, hypogonadism, premature menopause (before age 40), chronic malabsorption and chronic liver disease).

o Current smoker.

o Alcohol use of greater than 2 medium glasses of wine or beer per day.

o Body Mass Index (BMI) (less than 21 kg/m2).

o Other secondary causes of osteoporosis include the following:

 Oral glucocorticosteroid therapy for longer than 3 months

 Hypogonadism.

 Transplant history.

 Obesity surgery.

 Malabsorption disease.

 Aromatase therapy for breast cancer.

 Excess urinary calcium excretion.

 Vitamin D deficiency.

 Hypocalcemia.

 Multiple myeloma.

 Endocrine disorders such as:

 Hyperthyroidism.

 Cushing’s syndrome.

 Disorders of collagen structures.

 Renal failure (increase bone resorption, or decreased bone formation leading to renal osteodystrophy).

 Paget’s disease.

 Liver/biliary disease.

 Metastatic cancer involving bone.

• Medical management focused on lifestyle may be all that is needed for postmenopausal women who are at low risk for osteoporotic fracture. The North American Menopause Society (NAMS) recommends adding osteoporosis drug therapy in the following populations:

o All postmenopausal women who have had an osteoporotic vertebral or hip fracture.

o All postmenopausal women who have had BMD values consistent with osteoporosis (i.e., T-scores equal to or worse than -2.5) at the lumbar spine, femoral neck, or total hip region.

• In order to be covered by Medicare, a drug or biological must be safe and effective and otherwise reasonable and medically necessary.

o Drugs and biologicals approved for marketing by the Food and Drug Administration (FDA) are considered safe and effective when used for indications specified in the FDA labeling.

o The FDA labeling lists the safe and effective indications, dosage, and frequency of the agents.

o The Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual, Pub. 100-02, chapter 15, section 50 states the following:

 The Medicare program provides limited benefits for outpatient drugs that are furnished “incident to” a physician’s service provided that the drugs are not usually self-administered by the patients who take them. Generally, drugs and biologicals are covered only if all of the following requirements are met:

 They meet the definition of drugs or biologicals.

 They are of the type that are not usually self-administered.

 They meet all of the general requirements for coverage of items as incident to a physician’s services.

 They are reasonable and necessary for the diagnosis or treatment of the illness or injury for which they are administered according to accepted standards of medical practice.

 They are not excluded as noncovered immunizations.

 They have not been determined by the FDA to be less than effective.

• In addition to FDA approved indications, Medicare may consider coverage of off-label uses based on guidance provided in the Medicare Benefit Policy Manual, Pub. 100-02, chapter 15, section 50.4.2.

• This manual section indicates the following:

 

• Unlabeled Use of Drugs:

• FDA approved drugs used for indications other than what is indicated on the official label may be covered under Medicare if the contractor determines the use to be medically accepted, taking into consideration the major drug compendia, authoritative medical literature and/or accepted standards of medical practice.

o These decisions are made by the contractor on a case-by-case basis.

o If the drug use is not on the FDA label, and is not included in one of the compendium approved by CMS (American Hospital formulary Services (AHFS), Clinical Pharmacology, NCCN Drugs and Biologicals Compendium and/or Thomson Microdedex DrugDex®) and the Medicare Administrative Contractor Jurisdiction 9 (MAC J9) has not published an LCD or article covering the off-label use, the drug use would not be considered reasonable and necessary, and, therefore not allowed.

o Not only does the indication for the use of the drug need to meet medical necessity requirements, but the route of administration is also subject to medical necessity criteria.

• Contractors must continue to apply the policy that not only is the drug medically reasonable and necessary for any individual claim, but also that the route of administration is medically reasonable and necessary.

o That is, if a drug is available in both oral and injectable forms, the injectable form of the drug must be medically reasonable and necessary as compared to using the oral form.

• Medication given by injection (parenterally) is not covered if standard medical practice indicates that the administration of the medication by mouth (orally) is effective and is an accepted or preferred method of administration.

• Medical necessity is not demonstrated in the cases where a patient has not taken the oral form of a medication before the IV form of the drug, either for patient or provider convenience purposes, or for financial or emotional reasons, and these claims will be denied.

 

Bisphosphonates

 

• The following bisphosphonate injections (administered intravenously [IV]) will be considered medically reasonable and necessary when administered as outlined in this LCD.

o The coverage of IV bisphosphonates must be supported in the medical record.

o The documentation should include the following information:

 Criteria for the diagnosis of osteoporosis.

 History of treatment as related to progression of disease and ongoing risk factors.

 Description of treatment failure, or contraindication, or adverse side effects, of oral or self-administered drugs for osteoporosis as applicable to the patient that supports IV therapy in lieu of standard oral treatment protocol.

• The following IV bisphosphonate injections are considered medically reasonable and necessary when administered as outlined in this LCD:

o Ibandronate sodium injection (Boniva®).

o Zoledronic acid injection (Reclast®).

o Zoledronic acid injection (Zometa®).

• Boniva® is a bisphosphonate that inhibits osteoclast activity and reduces bone resorption and turnover, leading to, on average, a net gain in bone mass.

o Boniva®, like other bisphosphonates administered orally, may cause upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer. Treatment with IV bisphosphonates has been associated with renal toxicity manifested as deterioration in renal function and in rare cases, acute renal failure.

o Boniva® is not recommended for use in patients with severe renal impairment (serum creatinine>200 umol/L [2.3 mg/dL] or creatinine clearance < 30 mL/min).

o Patients who receive Boniva® injection should have serum creatinine measured prior to each dose.

o Hypocalcemia, hypovitaminosis D and other disturbances of bone and mineral metabolism must be effectively treated before starting therapy.

o Patients receiving this therapy must take supplemental calcium and vitamin D. Boniva® injection must only be administered intravenously by a healthcare professional.

• Given the oral equivalent and the availability of Boniva® tablets, and the Medicare manual language on the reasonable and necessary criteria for route of admission, the IV administration is allowed under the following circumstances:

o Patient has a diagnosis of esophageal stricture, achalasia, or other severe esophageal dysmotility disorder.

o Patient has a history of severe malabsorption making use of oral bisphosphonates ineffective.

o Patient has an inability to stand or sit upright for 60 minutes.

o Patient has documented adverse effects following the initiation of treatment of the oral form of the medication that required the withdrawal of the oral form of the medication.

FDA Indication for Boniva® Injection:

• Treatment of osteoporosis in postmenopausal women.

 

Off-label Indications for Boniva® Injection:

• Corticosteroid-induced osteoporosis.

o Paget’s disease.

o Bone metastases in patients with prostate cancer.

• Zoledronic acid (Reclast® and Zometa®) is a bisphosphonic acid, which is an inhibitor of osteoclastic bone resorption.

o Zoledronic acid binds to the bone matrix, which decreases osteoclastic activity, prevents bone resorption and skeletal calcium release induced by various stimulatory factors released by tumors.

 

FDA Indications for Reclast® Injection:

• Treatment of osteoporosis in postmenopausal women.

• Treatment of osteoporosis in men.

• Treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 12 months.

• Treatment for Paget’s disease of the bone with elevations in serum alkaline phosphatase of two times or higher than upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease, to induce remission (normalization of serum alkaline phosphatase).

 

FDA Indications for Zometa® Injection:

• Hypercalcemia of malignancy.

• Multiple myeloma.

• Bone metastases from solid tumors in conjunction with standard antineoplastic therapy, including:

o Bone metastases from multiple myeloma.

o Breast carcinoma.

o Prostate carcinoma.

o Other solid tumors.

• Note: Prostate cancer should have progressed after treatment with at least one hormonal therapy.

Off-label Indication for Zometa® Injection:

• Drug-induced osteopenia, secondary to androgen-deprivation therapy in prostate cancer patients (prophylaxis).

 

Monoclonal Antibodies - RANK ligand (RANKL) Inhibitors:

• The following monoclonal antibodies injections (administered subcutaneously [SQ]) will be considered medically reasonable and necessary when administered as outlined in this LCD.

o The coverage of SQ monoclonal antibodies must be supported in the medical record.

o The documentation should include the following information:

 Criteria for the diagnosis of osteoporosis, and history of treatment as related to progression of disease and ongoing risk factors, and description of treatment failure, or contraindication, or adverse side effects of oral or self-administered drugs for osteoporosis as applicable to the patient that supports monoclonal antibodies via SQ injection therapy in lieu of standard oral treatment protocol.

• Denosumab (Prolia® and Xgeva™) binds to RANKL, a transmembrane of soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption.

o Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors.

o Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.

• Prolia® (denosumab) is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of nuclear factor kappa – B ligand).

o It is produced in genetically engineered mammalian (Chinese hamster ovary) cells.

o Prolia® is given in a 1 mL single-use prefilled syringe with 60 mg denosumab and is administered every 6 months as a subcutaneous (SQ) injection into the upper arm, the upper thigh, or abdomen by a health care professional.

• Xgeva™ (denosumab) is a human IgG2 monoclonal antibody that binds to human RANKL that is produced in genetically engineered mammalian (Chinese hamster ovary) cells.

o Xgeva™ is administered every 4 weeks as a 120 mg SQ injection into the upper arm, upper thigh, or abdomen by a health care professional.

 

FDA indications for Prolia®:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture

• Treatment of bone loss in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer

• Treatment of bone loss in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

• High risk for fracture is defined as a history of osteoporotic fracture; or multiple risk factors for fracture; or patients who failed or are intolerant of other available osteoporosis therapy.

 

FDA indication for Xgeva™:

• Prevention of skeletal–related events in patients with bone metastasis from solid tumors.

 

Limitations:

• Combination use of a bisphosphonate and a monoclonal antibody for the treatment of osteoporosis during an episode of care is not considered reasonable and necessary, and therefore, is not covered.

o Combination use of IV and/or oral forms of bisphosphonate therapy as treatment for osteoporosis during an episode of care is not covered.

o An episode of care includes the duration and frequency of the IV drugs in accordance with FDA labels.

• Hypocalcemia, hypovitaminosis D, and other disturbances of bone and mineral metabolism must be effectively treated before starting therapy.

o Patients must receive supplemental calcium and vitamin D.

• For duration of treatment regarding the safety and effectiveness of the drugs listed in this LCD, the following information applies:

o IV Boniva® is based on data from clinical trials of 1 year duration.

o Prolia® is based on data from clinical trials of 2 years duration

o Reclast® is based on data from clinical trials of 3 years duration

o Xgeva ™ is based on data from clinical trials of median duration on-study of 13 months.

o Zometa® is based on data from clinical trials of 2 years duration.

• The optimal duration of the use of the drugs listed in this LCD has not been determined.

o It is expected that treatment with these drugs in a Medicare beneficiary meets the evidence-based peer reviewed literature and standards of care in the medical community.

 

• Boniva® is available in oral and IV forms.

o The IV form will be considered reasonable and necessary only for patients for whom oral therapy cannot be tolerated.

• Boniva® Injection is contraindicated for the following conditions:

o Severe renal impairment defined as patients with serum creatinine >200µmol/L [2.3 mg/dL] or

o creatinine clearance measured or estimated <30 mL/min

 Known hypersensitivity to Boniva® injections or to any of its excipients

 Uncorrected hypocalcemia

 

• Reclast® used for prevention without a confirmed diagnosis of osteoporosis in postmenopausal women will not be covered because it is not considered medically reasonable and necessary in the diagnosis and treatment of a specific illness or injury as defined in the Social Security Act, Section 1862(a)(1)(A) and as stated in CMS Publication 100-02, Medicare Benefit Policy Manual, chapter 15, section 50.4

• Reclast® is contraindicated in the following conditions:

o Hypocalcemia.

o Hypersensitivity to the active substance (zoledronic acid) or to any of the excipients

o Pregnancy and lactation.

o Patients receiving Zometa®.

o Severe renal impairment defined as patients with serum creatinine clearance measured or estimated <35 mL/min.

 

• Zometa® is contraindicated for the following conditions:

o Hypersensitivity to zoledronic acid or any component of Zometa®.

o Pregnancy and lactation.

 

• Prolia® is contraindicated for the following condition:

o Hypocalcemia.

 

 

• Xgeva™ is not indicated for the following indication:

o Prevention of skeletal related events in patients with multiple myeloma and other cancers of the blood.

 

CPT/HCPCS Codes

 

J0897 INJECTION, DENOSUMAB, 1 MG

J1740 INJECTION, IBANDRONATE SODIUM, 1 MG

J3487 INJECTION, ZOLEDRONIC ACID (ZOMETA), 1 MG

J3488 INJECTION, ZOLEDRONIC ACID (RECLAST), 1 MG

ICD-9 Codes that Support Medical Necessity

 

 

HCPCS Code J1740 (Boniva®)

 

198.5 Secondary malignant neoplasm of bone and bone marrow

731.0 Osteitis deformans without mention of bone tumor

733.01 Senile osteoporosis

733.09* Other osteoporosis

E932.0* Adrenal cortical steroids causing adverse effects in therapeutic use

 

*When reporting ICD-9-CM code 733.09, the ICD-9-CM coding manual requires a dual diagnosis. In this regard, when reporting ICD-9-CM code 733.09 (other, osteoporosis), ICD-9-CM code E932.0 (adrenal cortical steroids) must also be reported.

 

HCPCS Code J3487 (Zometa®)

 

198.5 Secondary malignant neoplasm of bone and bone marrow

203.00-203.02 Multiple myeloma

275.42 Hypercalcemia

733.90 Disorder of bone and cartilage, unspecified

 

HCPCS Code J3488 (Reclast®)

 

731.0 Osteitis deformans without mention of bone tumor

733.01 Senile osteoporosis

733.09* Other osteoporosis

E932.0* Adrenal cortical steroids causing adverse effects in therapeutic use

 

*When reporting ICD-9-CM code 733.09, the ICD-9-CM coding manual requires a dual diagnosis. In this regard, when reporting ICD-9-CM code 733.09 (other, osteoporosis), ICD-9-CM code E932.0 (adrenal cortical steroids) must also be reported.

 

 

HCPCS Code J0897 (Prolia®)

 

733.00-733.03 Osteoporosis

733.90 Disorder of bone and cartilage, unspecified

733.09 Other osteoporosis

 

For treatment of bone loss in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer, ICD-9-CM code 733.90 is reported with V10.3 and V07.52

 

V07.52 Use of aromatase inhibitors

V10.3 Personal history of malignant neoplasm of breast

 

For treatment of bone loss in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, ICD-9-CM code 733.90 is reported with V10.46 and V58.69

 

V10.46 Personal history of malignant neoplasm of prostate

V58.69 Long term (current) use of other medications]

 

HCPCS Code J0897 (Xgeva™)

 

198.5 Secondary malignant neoplasm of bone and bone marrow

 

XX000 Not Applicable

 

 

Documentation Requirements

• For all drugs outlined in this LCD:

 

• Medical record documentation must be maintained by the ordering/referring physician or the nonphysician practitioner and should include the following, and be available to Medicare upon request:

o The record must demonstrate the medical need for the use of the drug by clearly indicating the condition for which the drug is being used.

o The medical record must indicate that the treatment is based on diagnostic information and lab work completed to confirm the indications for use of the drug.

o The specific signs and symptoms must be documented to substantiate the FDA labeled or the FDA off labeled indications for the drug usage.

o For the osteoporosis indications for the drugs outlined in this LCD, the medical record must indicate that the patient has been examined for secondary causes of osteoporosis.

o An indication that the patient has been advised to take adequate calcium and vitamin D supplementation.

o For the osteoporosis indications for the drugs outlined in this LCD, an indication that the patient has been advised to practice regular weight bearing and muscle strengthening exercise to reduce risk of falls and fracture, and to avoid tobacco smoking and excessive alcohol intake.

o The medication administration record (MAR) including the name, date, time, route and dose of the drug administered to the patient.

o A statement that demonstrates oral health was discussed with the patient.

• This documentation is usually found in the history and physical and/or in the office/progress notes of the medical record.

o In addition, the MAR should be included indicating the name, date, time, route and amount of drug administered. The physician order should also be included.

 

• In addition, specific documentation is also required as outlined below:

 

• Bisphosphonate therapy:

• The following bisphosphonate injections (administered IV) are considered medically reasonable and necessary when administered as outlined in this LCD.

• The coverage of IV bisphosphonates must be supported in the medical record. The documentation should include the following information:

o Criteria for the diagnosis of osteoporosis

o History of treatment as related to progression of disease and ongoing risk factors

o Description of treatment failure of oral or self-administered drugs for osteoporosis as applicable to the patient that supports IV therapy in lieu of standard oral treatment protocol.

o An indication that the serum creatinine was measured prior to the administration of the drug.

o An indication that the oral health of the patient was discussed

 

• Boniva®

• The documentation must clearly state why IV Boniva® is being given as opposed to the oral form of the drug. Documentation should demonstrate if ONE of the following apply:

o Patient has a diagnosis of esophageal stricture, achalasia, or other severe esophageal dysmotility disorder.

o Patient has a history of severe malabsorption making use of oral bisphosphonates ineffective.

o Patient has an inability to stand or sit upright for 60 minutes.

o Patient had adverse side effects secondary to oral form of the drug that required the withdrawal of the oral from of the medication.

o An indication that the serum creatinine was measured before Boniva® was administered

o An indication that the patient does not have severe renal impairment (patients with severe renal impairment with serum creatinine >200 µmol/L [2.3 mg/dL] or creatinine clearance measured or estimated <30 mL/min should not receive Boniva® injection).

o Documentation to support that the drug was administered per IV route by a healthcare professional with a 3mg/3 mL bolus over 15 to 30 seconds every three months.

 

• Reclast® - All patients

o An indication that the patient received adequate hydration prior to treatment.

o An indication that the patient has a creatinine clearance of ≥35 mL/min or better.

o Documentation to support that the drug was administered one time in a year per IV route by a healthcare professional with 5 mg Reclast® infused IV over no less than 15 minutes given over a constant infusion rate with a 10 mL normal saline flush of the IV line following the infusion.

 

• Reclast® for Glucocorticoid-Induced Osteoporosis in Men and Women (must meet above criteria also)

o An indication that the patient is either initiating or continuing to take system glucocorticoids in a daily dosage of 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 12 months.

o An indication that the patient is taking at least 1200 mg calcium and 800-1000 IU vitamin D per day.

 

• Reclast® for Women or Men with Osteoporosis

o An indication that the patient is taking at least 1200 mg calcium and 800-1000 IU vitamin D per day.

 

• Reclast® for Paget’s Disease

o An indication that the patient has been instructed to take 1500 mg elemental calcium daily in divided doses (750 mg two times per day, or 500 mg three times per day) and 800 IU vitamin D per day, particularly in the 2 weeks following the administration of Reclast®

o An indication that the patient has one of the following:

 An elevated serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range.

 The patient is symptomatic.

 The patient is at risk for complications from the disease, to induce remission. (normalization of serum alkaline phosphatase) prior to treatment with Reclast®.

 

 

• Reclast® for Re-Treatment of Paget’s Disease

o An indication that the patient is experiencing a relapse based on serum alkaline phosphatase.

o An indication that the patient has failed to achieve normalization of their serum alkaline phosphatase.

o An indication that the patient has symptoms as dictated by current standard medical practice.

 

• Zometa®

o An indication that the patient is not on any other bisphosphonate medication(s).

o Documentation to support that the drug was administered per IV route by a healthcare professional with a dosage amount not exceeding 4 mg administered for no less than 15 minutes.

o An indication that the renal status of the patient has been monitored.

 

• Zometa® for Hypercalcemia of Malignancy

o An indication that the patient has an albumin-corrected serum calcium of ≥ 12 mg/dL (3.0 mmol/L).

o The date of the last treatment must be indicated.

 

• Zometa® for Multiple Myeloma and Metastatic Bone Lesions of Solid Tumors

o An indication that for the patient with a creatinine clearance of > 60 mL/min, a 4 mg IV infusion over no less than 15 minutes was administered every 3-4 weeks by a healthcare provider.

o An indication that the patient was coadministered oral calcium supplements of 500 mg and a multiple vitamin containing 400 IU of vitamin D per day.

 

• Prolia®

• Prolia® for Women with Postmenopausal Osteoporosis

o An indication that the patient meets the definition of high risk for fracture.

o An indication that the patient has failed or is intolerant of other available osteoporotic therapy.

o An indication that the patient received a single dose of 60 mg SQ Prolia® which was administered by a healthcare professional into the upper arm, the upper thigh or the abdomen once in 6 months.

o An indication that the patient was instructed to take 1000 mg of calcium and at least 400 IU of vitamin D per day.

 

• Prolia® for Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer

o An indication that the patient is a woman receiving adjuvant aromatase inhibitor therapy for breast cancer.

o An indication that the patient received a single dose of 60 mg SQ Prolia® which was administered by a healthcare professional into the upper arm, the upper thigh or the abdomen once in 6 months.

o An indication that the patient was instructed to take 1000 mg of calcium and at least 400 IU of vitamin D per day.

• Prolia® for Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Nonmetastatic Prostate Cancer

o An indication that the patient is a man receiving androgen deprivation therapy for prostate cancer.

o An indication that the patient received a single dose of 60 mg SQ Prolia® which was administered by a healthcare professional into the upper arm, the upper thigh or the abdomen once in 6 months.

o An indication that the patient was instructed to take 1000 mg of calcium and at least 400 IU of vitamin D per day.

 

• Xgeva™

• Xgeva™ for the prevention of skeletal-related events in patients with Bone Metastasis from solid tumors

o An indication that the patient received a single dose dose of 120 mg SQ Xgeva™ which was administered by a healthcare professional into the upper arm, the upper thigh or the abdomen once every 4 weeks.

o An indication that the patient is taking calcium and vitamin D supplements as necessary to treat or prevent hypocalcemia.

•

Boniva®

o Boniva® injection must be administered by intravenous route only by a healthcare professional.

o The recommended dose of Boniva® injection is 3 mg/3 mL IV bolus over 15 to 30 seconds once every three months.

o Patients with severe renal impairment with serum creatinine >200 µmol/L (2.3 mg/dL) or creatinine clearance measured or estimated <30 mL/min should not receive Boniva® injection.

o Patients taking Boniva® must receive supplemental calcium and vitamin D.

 

• Reclast®

o Reclast® contains the same active ingredient found in Zometa®. A patient that is already receiving Zometa® should not be treated with Reclast®.

o Patients must receive adequate hydration prior to the administration of Reclast®.

o For patients with creatinine clearance ≥35 mL/min the recommended dose of Reclast® is 5 mg infused intravenously once a year over no less than 15 minutes given over a constant infusion rate with a 10 mL normal saline flush of the IV line following the infusion.

 

• Glucocorticoid-Induced Osteoporosis

o The recommended regimen is a 5 mg of Reclast® IV infused once a year over no less than 15 minutes given over a constant infusion rate with a 10 mL normal saline flush of the IV line following the infusion.

o An average of at least 1200 mg calcium and 800-1000 IU vitamin D per day is recommended for patients with glucocorticoid-induced osteoporosis receiving Reclast®.

 

• Osteoporosis in Postmenopausal Women and Men

o For treatment of osteoporosis in postmenopausal women and men, 5 mg of Reclast® IV infused once a year over no less than 15 minutes given over a constant infusion rate is recommended with a 10 mL normal saline flush of the IV line following the infusion.

o 1200 mg calcium and 800-1000 IU vitamin D per day.

 

• Paget’s Disease

o The recommended dose is 5 mg of Reclast® IV infused once a year over no less than 15 minutes given over a constant infusion rate with a 10 mL normal saline flush of the IV line following the infusion.

o To reduce the risk of hypocalcemia, all patients with Paget’s disease should receive 1500 mg elemental calcium daily in divided doses (750 mg two times a day, or 500 mg three times a day) and 800 IU vitamin D daily, particularly in the 2 weeks following the administration of Reclast®.

 

• Zometa®

o Zometa® contains the same active ingredient found in Reclast®. A patient that is already receiving Zometa® should not be treated with Reclast®.

o A single dose of Zometa® should not exceed 4mg and must be given intravenously for no less than 15 minutes.

o Retreatment with Zometa® 4 mg may be considered if serum calcium does not return to normal or remain normal after treatment.

o It is recommended that a minimum of 7 days elapse before re-treatment to allow for full response to the initial dose.

o Renal function must be carefully monitored in all patients receiving Zometa® and possible deterioration in renal function must be assessed prior to re-treatment with Zometa®

 

• Hypercalcemia of Malignancy

o Zometa® is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected serum calcium ≥ 12 mg/dL [3.0 mmol/L].

o The maximum recommended dose of Zometa® for this indication is 4 mg dose given as a single-dose IV infusion over no less than 15 minutes.

o Patients should have their serum creatinine assessed prior to each treatment.

o Patients should be adequately hydrated prior to the administration of Zometa®.

o Retreatment may be considered if serum calcium does not return to normal or remain normal after the initial treatment.

o A minimum of 7 days should elapse prior to retreatment to allow for full response to the initial dose.

 

• Multiple Myeloma and Metastatic Bone Lesions of Solid Tumors

o The recommended dose of Zometa® for these indications for patients with creatinine clearance >60 mL/min is 4 mg infused over no less than 15 minutes every 3 to 4 weeks.

o Patients should take an oral calcium supplement of 500 mg and a multiple vitamin containing 400 IU of Vitamin D daily.

 

 

• Monoclonal Antibodies - RANK ligand (RANKL) Inhibitors:

 

• Prolia®

o Postmenopausal Women with Osteoporosis at High Risk for Fracture

o Prolia® for Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer

o Prolia® for Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Nonmetastatic Prostate Cancer

 Prolia® is a single dose 60 mg subcutaneous (SQ) injection administered by a healthcare professional into the upper arm, the upper thigh, or the abdomen once every six months.

 Patients receiving Prolia® are instructed to take 1000 mg of calcium and at least 400 IU of vitamin D per day.

 

• Xgeva™

 

• Prevention of Skeletal-Related Events in Patients with Bone Metastisis from Solid Tumors

o Xgeva™ is a single dose of 120 mg SQ injection administered by a healthcare professional into the upper arm, the upper thigh, or the abdomen once every 4 weeks.

o Patients receiving Xgeva™ should take calcium and vitamin D as necessary to treat or prevent hypocalcemia.

 

Treatment Logic

• Osteoporosis is characterized by decreased bone mass and increased fracture risk, most commonly at the spine, hip, and wrist.

• The diagnosis can be confirmed by a finding of low bone mass, evidence of fracture on x-ray, a history of osteoporotic fracture, or height loss or kyphosis indicative of vertebral fracture.

• While osteoporosis occurs in both men and women, it is most common among women following menopause.

• In healthy people, bone formation and resorption are closely linked; old bone is resorbed and replaced by newly formed bone.

•  In postmenopausal osteoporosis, bone resorption exceeds bone formation, leading to bone loss and increased risk of fracture.

Sources of Information and Basis for Decision

 

American College of Rheumatology. (2008). New NOF guidelines and the WHO fracture assessment tool or FRAX. Retrieved from: http://www.rheumatology.org/publications/hotline/03_18_flax.asp

 

American College of Rheumatology. (N.D.). Glucocorticoid-induced osteoporosis. Retrieved from: http://www.rheumatology.org/publications/hotline/03_18_flax.asp

 

Boniva® (ibandronate sodium) prescribing information. (2010). Genentech, U.S.A., Inc.

 

Clinical Pharmacology Web site. (2011). Denosumab. Retrieved from: http://clinicalpharmacology.com

 

Clinical Pharmacology Web site. (2011). Ibandronate sodium. Retrieved from: http://clinicalpharmacology.com

 

Clinical Pharmacology Web site. (2011). Zoledronic acid. Retrieved from: http://clinicalpharmacology.com

 

FCSO LCD 32100, Bisphosphonates (Intravenous [IV]) and Monoclonal Antibodies in the Treatment of Osteoporosis and Their Other Indications, 05/01/2012. The official local coverage determination (LCD) is the version on the Medicare coverage database at www.cms.gov/medicare-coverage-database/.

 

North American Menopause Society, (2010). Management of osteoporosis in postmenopausal women: 2010 position statement. Retrieved from: http://www.medscape.com/viewarticle/714984_print

 

Prolia™ (denosumab) prescribing information. (2010). Amgen, Inc.

 

Prolia® (denosumab) prescribing information. (2011). Amgen, Inc.

 

Reclast® (zoledronic acid) Injection prescribing information. (2011). Novartis Pharmaceuticals, Corp.

 

World Health Organization (2007). WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level. Summary meeting report, Brussels, Belgium, May 5-7, 2004. Retrieved from http://www.worldhealthorganization.org

 

Xgeva™ (densoumab) prescribing information. (2010). Amgen, Inc.

 

Zometa® (zoledronic acid) Injection prescribing information. (2011). Novartis Pharmaceuticals, Corp.

 

05/01/2012

The official local coverage determination (LCD) is the version on the Medicare coverage database at www.cms.gov/medicare-coverage-database/.

 

AMA CPT / ADA CDT Copyright Statement

CPT codes, descriptions and other data only are copyright 2011 American Medical Association (or such other date of publication of CPT). All Rights Reserved. Applicable FARS/DFARS Clauses Apply. Current Dental Terminology, (CDT) (including procedure codes, nomenclature, descriptors and other data contained therein) is copyright by the American Dental Association. © 2002, 2004 American Dental Association. All rights reserved. Applicable FARS/DFARS apply.

 

CMS LCD L32100 Bisphosphonates (Intravenous [IV]) and Monoclonal Antibodies in the Treatment of Osteoporosis and Their Other Indications