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  • OSTEOPOROSIS MEDICATIONS
    • NOTE: This page is intended to be a quick reference for properties of commonly used osteoporosis medications. It is NOT a comprehensive review of each medication. Other drug interactions, side effects, precautions, and contraindications may exist for each drug. All information pertains to adult patients only.

BISPHOSPHONATES OTHER MEDICATIONS





Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Alendronate

(Fosamax®)
(Fosamax® PLUS D)
(Binosto®)
Fosamax® - tablet
  • 5 mg
  • 10 mg
  • 35 mg
  • 40 mg
  • 70 mg

Fosamax® PLUS D tablet
  • Alendronate : Cholecalciferol
    • 70 mg : 2800 IU
    • 70 mg : 5600 IU

Binosto®
effervescent tablet

  • 70 mg
Fosamax
Osteoporosis treatment (postmenopausal women)
  • Dosing: 70 mg once weekly or 10 mg once daily

Osteoporosis prevention (postmenopausal women)
  • Dosing: 35 mg once weekly or 5 mg once daily

Osteoporosis treatment (men)
  • Dosing: 70 mg once weekly or 10 mg once daily

Corticosteroid-induced osteoporosis
  • Dosing: 5 mg once daily
  • For postmenopausal women not receiving estrogen, recommended dose is 10 mg once daily
Paget's disease
  • Dosing: 40 mg once daily for 6 months
  • Re-treatment may be considered after a 6 month break in patients who relapse

Fosamax PLUS D
Osteoporosis treatment (postmenopausal women)
  • Dosing: 70 mg/5600 IU once weekly
  • 70 mg/5600 IU is the preferred dose. 70 mg/2800 IU dose may also be used.

Osteoporosis treatment (men)
  • Dosing: 70 mg/5600 IU once weekly
  • 70 mg/5600 IU is the preferred dose. 70 mg/2800 IU dose may also be used.

Binosto
Osteoporosis treatment (postmenopausal women)
  • Dosing: 70 mg once weekly

Osteoporosis treatment (men)
  • Dosing: 70 mg once weekly
Fosamax®
YES/$
(1 month)

Fosamax® PLUS D
NO/$$$$
(1 month)

Binosto®
NO/$$$$
(1 month)

Fosamax and Fosamax PLUS D
  • Take Fosamax at least 30 minutes before the first food, beverage, or medication of the day with plain water only

  • Swallow with at least 6 - 8 oz of water

  • Do not lie down for at least 30 minutes and until after the first food of the day

  • If dose is missed, take one dose on morning after remembering. Resume taking on originally scheduled day. Do not take 2 doses in 1 day.

Binosto
  • Take Binosto at least 30 minutes before the first food, beverage, or medication of the day with plain water only

  • Dissolve tablet in 4 oz of room temperature water

  • Wait at least 5 minutes after the effervescence stops and then stir the solution for 10 seconds

  • Do not lie down for at least 30 minutes and until after the first food of the day

  • If dose is missed, take one dose on morning after remembering. Resume taking on originally scheduled day. Do not take 2 doses in 1 day.

Mechanism of action
  • Bisphosphonates enter osteoclasts and inhibit an enzyme called farnesyl pyrophosphate synthase (FPPS)

  • Inhibition of FPPS disrupts the attachment of osteoclasts to the bone surface. This stops absorption and leads to early cell death. [5]

FDA-approved indications

Fosamax
  • Treatment and prevention of osteoporosis in postmenopausal women
  • Treatment to increase bone mass in men with osteoporosis
  • Treatment of glucocorticoid-induced osteoporosis
  • Treatment of Paget's disease of bone

Fosamax PLUS D and Binosto
  • Treatment of osteoporosis in postmenopausal women
  • Treatment to increase bone mass in men with osteoporosis
In studies, the incidence of side effects with alendronate was no different than placebo
  • Calcium supplements/antacids - co-administration of alendronate with calcium, antacids, or other medications containing multivalent cations will interfere with the absorption of alendronate. Wait at least 30 minutes after taking alendronate before taking other medications.
  • Aspirin - aspirin may increase the risk of upper gastrointestinal adverse events when taken with alendronate
  • NSAIDs (e.g. ibuprofen, naprosyn) - in trials, concomitant NSAIDs did not increase the risk of upper gastrointestinal adverse events when taken with alendronate. However, the manufacturer recommends using caution with these medications.
  • Drugs that inhibit the absorption of Vitamin D - Olestra, mineral oils, orlistat, and bile acid sequestrants (e.g., cholestyramine, colestipol) may impair the absorption of vitamin D. Additional Vitamin D may be necessary.
  • Drugs that increase the metabolism of Vitamin D - anticonvulsants, cimetidine, and thiazides may increase the metabolism of vitamin D. Additional Vitamin D may be necessary.
  • Bone-imaging agents - bisphosphonates may interfere with the use of bone-imaging agents
  • Esophageal abnormalities that delay emptying (e.g. achalasia, stricture)
    - DO NOT USE
  • Inability to stand or sit upright for at least 30 minutes - DO NOT USE
  • Hypocalcemia - DO NOT USE. Hypocalcemia must be corrected before starting alendronate. In trials, transient decreases in calcium and phosphate were observed in 18% of patients taking alendronate and in 12% taking placebo. The risk appears to be greater in patients with Paget's disease and in patients taking corticosteroids.
  • Upper gastrointestinal (GI) disorders - bisphosphonates may cause local irritation to the upper GI mucosa. Use caution in patients with upper GI disorders such as Barrett's esophagus, dysphagia, esophageal diseases, gastritis, duodenitis, and ulcers. Patients should discontinue their bisphosphonate and notify their provider if upper GI symptoms occur.
  • Osteonecrosis of the jaw (ONJ) - bisphosphonates have been associated with ONJ. ONJ can occur spontaneously, but is generally associated with tooth extraction and/or local infection. Risk factors for ONJ include tooth extraction, dental implants, boney surgery, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, and ill-fitting dentures. Discontinuing bisphosphonates before dental procedures may decrease the risk of ONJ.
  • Atypical femoral fractures - bisphosphonates have been associated with a slight increase in risk for atypical subtrochanteric and diaphyseal femoral fractures. In one study, the increase in absolute risk was 5 cases per 10,000 patient-years. Concomitant corticosteroids may increase the risk. A prodromal phase of dull, aching thigh pain may precede the fracture for weeks to months. [6]
  • Severe musculoskeletal pain - in rare cases, severe bone, muscle, and joint pain has been reported in patients taking bisphosphonates. Time to onset of symptoms varied from days to months after starting the drug.
  • Vitamin D deficiency - treat if present to ensure proper mineral metabolism
  • Patients sensitive to sodium (Binosto) - each Binosto tablet contains 650 mg of sodium. Avoid in susceptible patients (e.g. uncontrolled CHF)
  • Glucocorticoid-induced osteoporosis - the risk/benefit of alendronate for treatment of osteoporosis in patients taking daily doses of glucocorticoids less than 7.5 mg of prednisone or equivalent has not been established
  • Liver disease - no dose adjustment necessary
  • Kidney disease
    • CrCl ≥ 35 ml/min: no dose adjustment necessary
    • CrCl < 35 ml/min: DO NOT USE

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Ibandronate

(Boniva®)
Boniva® - tablet
  • 150 mg

Boniva® injection
  • 3 mg prefilled syringe (1 mg/ml)
Boniva tablet
Osteoporosis prevention and treatment in
postmenopausal women

  • Dosing: 150 mg once monthly on the same day each month
  • Missed doses:
    • If the next scheduled Boniva day is more than 7 days away, take one Boniva 150 mg tablet in the morning following the date that it is remembered
    • If the next scheduled Boniva day is only 1 to 7 days away, wait until the subsequent month's scheduled Boniva day to take the tablet

Boniva injection
Osteoporosis treatment in postmenopausal women
  • Dosing: 3 mg intravenously every 3 months
  • Dose is given over a period of 15 - 30 seconds
  • Missed doses:
    • If the dose is missed, administer as soon as it can be re-scheduled. Thereafter, Boniva injection should be scheduled every 3 months from the date of the last injection.
Boniva tablet®
YES/$
(1 month)

Boniva® injection
YES/$$$$
(3 month)

Boniva tablet
  • Take at least 60 minutes before the first food or drink (other than water) of the day. Take at least 60 minutes before any medication or supplement.

  • Swallow tablet whole with a full glass of plain water (6 to 8 oz) while standing or sitting in an upright position. Avoid lying down for 60 minutes after taking.

Boniva injection
  • Must be administered intravenously by a healthcare professional

  • Do not use prefilled syringes with particulate matter or discoloration
Mechanism of action
  • Bisphosphonates enter osteoclasts and inhibit an enzyme called farnesyl pyrophosphate synthase (FPPS)

  • Inhibition of FPPS disrupts the attachment of osteoclasts to the bone surface. This stops absorption and leads to early cell death. [5]

FDA-approved indications

Boniva tablet
  • Treatment and prevention of postmenopausal osteoporosis

Boniva injection
  • Treatment of postmenopausal osteoporosis
NOTE: Only side effects that occurred at an incidence ≥ 2% more than placebo are listed. Data is from 2.5 mg/day dosing trial.

  • Back pain - 14%, P - 12%
  • Upset stomach - 12%, P - 10%
  • Bronchitis - 10%, P - 7%
  • Pain in extremity - 8%, P - 6%
  • Diarrhea - 7%, P - 5%
  • Pneumonia - 6%, P - 4%
  • UTI - 6%, P - 4%
  • Weakness - 4%, P - 2%
  • Tooth disorder - 4%, P - 2%
  • Injection site reactions (injection) - 1.7%, P - 0.2%
  • Calcium supplements/antacids - co-administration of ibandronate with calcium, antacids, or other medications containing multivalent cations will interfere with the absorption of ibandronate. Wait at least 60 minutes after taking ibandronate before taking other medications.
  • Aspirin - aspirin may increase the risk of upper gastrointestinal adverse events when taken with bisphosphonates
  • NSAIDs (e.g. ibuprofen, naprosyn) - NSAIDs may increase the risk of upper gastrointestinal adverse events when taken with bisphosphonates
  • Bone-imaging agents - bisphosphonates may interfere with the use of bone-imaging agents
  • Esophageal abnormalities that delay emptying (e.g. achalasia, stricture)
    - DO NOT USE
  • Inability to stand or sit upright for at least 60 minutes - DO NOT USE
  • Hypocalcemia - DO NOT USE. Hypocalcemia must be corrected before starting bisphosphonates. Bisphosphonates may cause a decrease in calcium levels.
  • Upper gastrointestinal (GI) disorders - bisphosphonates may cause local irritation to the upper GI mucosa. Use caution in patients with upper GI disorders such as Barrett's esophagus, dysphagia, esophageal diseases, gastritis, duodenitis, and ulcers. Patients should discontinue their bisphosphonate and notify their provider if upper GI symptoms occur.
  • Osteonecrosis of the jaw (ONJ) - bisphosphonates have been associated with ONJ. ONJ can occur spontaneously, but is generally associated with tooth extraction and/or local infection. Risk factors for ONJ include tooth extraction, dental implants, boney surgery, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, and ill-fitting dentures. Discontinuing bisphosphonates before dental procedures may decrease the risk of ONJ.
  • Atypical femoral fractures - bisphosphonates have been associated with a slight increase in risk for atypical subtrochanteric and diaphyseal femoral fractures. In one study, the increase in absolute risk was 5 cases per 10,000 patient-years. Concomitant corticosteroids may increase the risk. A prodromal phase of dull, aching thigh pain may precede the fracture for weeks to months. [6]
  • Severe musculoskeletal pain - in rare cases, severe bone, muscle, and joint pain has been reported in patients taking bisphosphonates. Time to onset of symptoms varied from days to months after starting the drug.
  • Vitamin D deficiency - treat if present to ensure proper mineral metabolism
  • Anaphylactic reactions (injection) - anaphylactic reactions have occurred in patients receiving Boniva injection. Administer under proper supervision.
  • Kidney failure (injection) - renal toxicity including renal failure has been associated with intravenous bisphosphonates. Use caution.
  • Liver disease - no dose adjustment necessary
  • Kidney disease
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl < 30 ml/min: DO NOT USE

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Risedronate

(Actonel®)
(Atelvia®)
Actonel® - tablet
  • 5 mg
  • 30 mg
  • 35 mg
  • 75 mg
  • 150 mg

Atelvia®
delayed-release tablet

  • 35 mg
Actonel tablet
Osteoporosis prevention and treatment in
postmenopausal women

  • One of the following:
    • 5 mg once daily
    • 35 mg once weekly
    • 75 mg taken on 2 consecutive days for a total of two tablets each month
    • 150 mg once monthly

Osteoporosis treatment in men
  • 35 mg once weekly

Glucocorticoid-induced osteoporosis (treatment and prevention)
  • 5 mg once daily

Paget's disease
  • 30 mg once daily for 2 months
  • Re-treatment may be considered after a 2 month break in patients who relapse

Atelvia tablet
Osteoporosis treatment in postmenopausal women
  • Dosing: 35 mg once weekly

Actonel and Atelvia missed doses
35 mg once weekly (Actonel and Atelvia)
  • Take morning after remembering. Resume taking on originally scheduled day. Do not take 2 tablets on same day.
75 mg on 2 consecutive days each month
  • If next month's doses are > 7 days away, take missing dose(s) and resume originally scheduled dosing. Do not take more than 2 tablets within 7 days.
  • If next month's doses are within 7 days away, wait until next month's scheduled doses and resume original schedule
150 mg dose
  • If next month's dose is > 7 days away, take missing dose and resume originally scheduled dosing. Do not take more than 1 tablet within 7 days.
  • If next month's dose is within 7 days away, wait until next month's scheduled dose and resume original schedule
Actonel®
YES/$$-$$$
(1 month)

Atelvia®
NO/$$$$
(1 month)

Actonel
  • Take at least 30 minutes before the first food or drink (other than water) of the day. Take at least 30 minutes before any medication or supplement.

  • Swallow tablet whole with a full glass of plain water (6 to 8 oz) while standing or sitting in an upright position. Avoid lying down for 30 minutes after taking.

Atelvia
  • Take immediately following breakfast. Do not take under fasting conditions because of increased risk of abdominal pain.

  • Swallow tablet whole with at least 4 oz of plain water while standing or sitting in an upright position. Avoid lying down for 30 minutes after taking.
Mechanism of action
  • Bisphosphonates enter osteoclasts and inhibit an enzyme called farnesyl pyrophosphate synthase (FPPS)

  • Inhibition of FPPS disrupts the attachment of osteoclasts to the bone surface. This stops absorption and leads to early cell death. [5]

FDA-approved indications

Actonel
  • Treatment and prevention of postmenopausal osteoporosis
  • Treatment of osteoporosis in men
  • Treatment and prevention of glucocorticoid-induced osteoporosis
  • Paget's disease

Atelvia
  • Treatment of postmenopausal osteoporosis
In clinical trials with Actonel 5 mg/day, only abdominal pain occurred at an incidence ≥ 2% more than placebo (12.2% vs 9.9%)
  • Calcium supplements/antacids - co-administration of risedronate with calcium, antacids, or other medications containing multivalent cations will interfere with the absorption of risedronate. Wait at least 30 minutes after taking risedronate before taking other medications.
  • H2 blockers and PPIs (Atelvia) - acid-reducing drugs like H2 blockers (e.g. famotidine) and PPIs (e.g. omeprazole) may increase exposure to Atelvia. Atelvia should not be taken with these drugs.
  • Aspirin - aspirin may increase the risk of upper gastrointestinal adverse events when taken with bisphosphonates. In risedronate trials, adverse upper GI events among patients taking aspirin were no different between risedronate users and placebo.
  • NSAIDs (e.g. ibuprofen, naprosyn) - NSAIDs may increase the risk of upper gastrointestinal adverse events when taken with bisphosphonates. In risedronate trials, adverse upper GI events among patients taking NSAIDs were no different between risedronate users and placebo.
  • Bone-imaging agents - bisphosphonates may interfere with the use of bone-imaging agents
  • Esophageal abnormalities that delay emptying (e.g. achalasia, stricture)
    - DO NOT USE
  • Inability to stand or sit upright for at least 30 minutes - DO NOT USE
  • Hypocalcemia - DO NOT USE. Hypocalcemia must be corrected before starting bisphosphonates. Bisphosphonates may cause a decrease in calcium levels.
  • Upper gastrointestinal (GI) disorders - bisphosphonates may cause local irritation to the upper GI mucosa. Use caution in patients with upper GI disorders such as Barrett's esophagus, dysphagia, esophageal diseases, gastritis, duodenitis, and ulcers. Patients should discontinue their bisphosphonate and notify their provider if upper GI symptoms occur.
  • Osteonecrosis of the jaw (ONJ) - bisphosphonates have been associated with ONJ. ONJ can occur spontaneously, but is generally associated with tooth extraction and/or local infection. Risk factors for ONJ include tooth extraction, dental implants, boney surgery, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, and ill-fitting dentures. Discontinuing bisphosphonates before dental procedures may decrease the risk of ONJ.
  • Atypical femoral fractures - bisphosphonates have been associated with a slight increase in risk for atypical subtrochanteric and diaphyseal femoral fractures. In one study, the increase in absolute risk was 5 cases per 10,000 patient-years. Concomitant corticosteroids may increase the risk. A prodromal phase of dull, aching thigh pain may precede the fracture for weeks to months. [6]
  • Severe musculoskeletal pain - in rare cases, severe bone, muscle, and joint pain has been reported in patients taking bisphosphonates. Time to onset of symptoms varied from days to months after starting the drug.
  • Vitamin D deficiency - treat if present to ensure proper mineral metabolism
  • Liver disease - no dose adjustment necessary
  • Kidney disease
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl < 30 ml/min: DO NOT USE

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Zoledronic acid

(Reclast®)
Zoledronic acid® injection
  • 5 mg/100 ml
Osteoporosis treatment in
postmenopausal women

  • 5 mg via intravenous infusion once yearly

Osteoporosis prevention in
postmenopausal women

  • 5 mg intravenous infusion once every 2 years

Osteoporosis treatment in men
  • 5 mg intravenous infusion once yearly

Glucocorticoid-induced osteoporosis (treatment and prevention)
  • 5 mg intravenous infusion once yearly

Paget's disease
  • 5 mg intravenous infusion
  • Consider retreatment in patients who relapse
Reclast®
YES/$$$$
(1 year)

  • Patients must be appropriately hydrated before infusion

  • Infuse over no less than 15 minutes at a constant rate

  • Flush line with 10 ml of normal saline after infusion

  • Administering acetaminophen after infusion may decrease incidence of acute-phase reactions

  • Store at room temperature
Mechanism of action
  • Bisphosphonates enter osteoclasts and inhibit an enzyme called farnesyl pyrophosphate synthase (FPPS)

  • Inhibition of FPPS disrupts the attachment of osteoclasts to the bone surface. This stops absorption and leads to early cell death. [5]

FDA-approved indications
  • Treatment and prevention of postmenopausal osteoporosis
  • Treatment of osteoporosis in men
  • Treatment and prevention of glucocorticoid-induced osteoporosis
  • Paget's disease
NOTE: only side effects that occurred at an incidence ≥ 2% more than placebo are listed

  • Joint pain - 23.8%, P - 20.4%
  • Fever - 17.9%, P - 4.6%
  • Headache - 12.4%, P - 8.1%
  • Muscle pain - 11.7%, P - 3.7%
  • Influenza-like illness - 8.8%, P - 2.7%
  • Nausea - 8.5%, P - 5.2%
  • Bone pain - 5.8%, P - 2.3%
  • Chills - 5.4%, P - 1%
  • Weakness - 5.3%, P - 2.9%
  • Pain - 3.3%, P - 1.3%
  • Aminoglycosides - aminoglycosides may potentiate the decrease in calcium levels seen with bisphosphonates. Use caution.
  • Loop diuretics - loop diuretics may potentiate the decrease in calcium levels seen with bisphosphonates. Use caution.
  • Nephrotoxic drugs - use caution when administering zoledronic acid with other potentially nephrotoxic drugs
  • Renally-excreted drugs - zoledronic acid may impair renal function. Use caution when given with drugs that are primarily renally excreted.
  • Bone-imaging agents - bisphosphonates may interfere with the use of bone-imaging agents
  • Hypocalcemia - DO NOT USE. Hypocalcemia must be corrected before starting bisphosphonates. Bisphosphonates may cause a decrease in calcium levels.
  • Acute renal impairment - DO NOT USE. Zoledronic acid may worsen kidney function.
  • Dehydration - DO NOT USE until proper hydration has been established
  • Renal impairment - use caution in patients with renal impairment. Acute renal toxicity including renal failure have been reported in patients receiving zoledronic acid. Risk may be higher with advanced age, concomitant nephrotoxic medications, concomitant diuretic therapy, and/or severe dehydration.
  • Osteonecrosis of the jaw (ONJ) - bisphosphonates have been associated with ONJ. ONJ can occur spontaneously, but is generally associated with tooth extraction and/or local infection. Risk factors for ONJ include tooth extraction, dental implants, boney surgery, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, and ill-fitting dentures. Discontinuing bisphosphonates before dental procedures may decrease the risk of ONJ.
  • Osteonecrosis of other bones - case reports of osteonecrosis in other bones including the femur, hip, knee, ankle, wrist, and humerus have been reported in patients receiving zoledronic acid.
  • Atypical femoral fractures - bisphosphonates have been associated with a slight increase in risk for atypical subtrochanteric and diaphyseal femoral fractures. In one study, the increase in absolute risk was 5 cases per 10,000 patient-years. Concomitant corticosteroids may increase the risk. A prodromal phase of dull, aching thigh pain may precede the fracture for weeks to months. [6]
  • Severe musculoskeletal pain - in rare cases, severe bone, muscle, and joint pain has been reported in patients taking bisphosphonates. Time to onset of symptoms varied from days to months after starting the drug.
  • Asthma - there have been reports of bronchoconstriction in aspirin-sensitive patients receiving bisphosphonates
  • Vitamin D deficiency - treat if present to ensure proper mineral metabolism
  • Liver disease - no dose adjustment necessary
  • Kidney disease
    • CrCl ≥ 35 ml/min: no dose adjustment necessary
    • CrCl < 35 ml/min: DO NOT USE




Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Calcitonin

(Miacalcin®)
(Fortical®)
Miacalcin® - nasal spray
  • 200 IU/spray
  • Comes in 3.7 ml bottle that delivers 0.09 ml/spray

Fortical® - nasal spray
  • 200 IU/spray
  • Comes in 3.7 ml bottle that delivers 0.09 ml/spray

Miacalcin® - injection
  • 200 IU/ml
  • Comes in 2 ml vial
Miacalcin nasal spray
Osteoporosis treatment in postmenopausal women
  • Dosing: 1 spray (200 IU) once daily
  • Alternate nostrils daily

Fortical nasal spray
Osteoporosis treatment in postmenopausal women
  • Dosing: 1 spray (200 IU) once daily
  • Alternate nostrils daily

Miacalcin injection
Osteoporosis treatment in postmenopausal women
  • Dosing: 100 IU (0.5 ml) given subcutaneously or intramuscularly once daily

Paget's disease
  • Dosing: 100 IU (0.5 ml) given subcutaneously or intramuscularly once daily

Hypercalcemia
  • Starting: 4 IU/kg every 12 hours by subcutaneous or intramuscular injection
  • If response is not adequate after 1 - 2 days, may increase to 8 IU/kg every 12 hours. If response is still not adequate after 2 more days, may increase to 8 IU/kg every 6 hours
Miacalcin® nasal spray
YES/$$
(1 month)

Fortical® nasal spray
NO/$$
(1 month)

Miacalcin® vial
NO/$$$$
(1 month)

Miacalcin nasal spray
  • Store unopened bottle in refrigerator

  • Once opened, store at room temperature for up to 35 days

  • Allow bottle to reach room temperature before using

  • Before first use, prime until full spray is emitted. Do not prime again.

Fortical nasal spray
  • Store unopened bottle in refrigerator

  • Once opened, store at room temperature

  • Allow bottle to reach room temperature before using

  • Before first use, prime bottle at least 5 times until a full spray is emitted. Do not prime again.

Miacalcin injection
  • Store vial in refrigerator

  • Solution should be clear and colorless

  • If volume of injection exceeds 2 ml, intramuscular injection is preferred
Mechanism of action
  • Calcitonin is an endogenous hormone that inhibits osteoclastic bone resorption

FDA-approved indications
Miacalcin and Fortical
  • Treatment of postmenopausal osteoporosis in women who are > 5 years postmenopause

Miacalcin injection
  • Treatment of postmenopausal osteoporosis in women who are > 5 years postmenopause
  • Paget's disease
  • Hypercalcemic emergencies
NOTE: only side effects that occurred at an incidence of ≥ 3% and more than placebo are listed

  • Runny nose - 12%, P - 7%
  • Back pain - 5%, P - 2%
  • Injection site reactions (injection) - 10%
  • Lithium - calcitonin may increase renal excretion of lithium. Monitor lithium levels with concomitant therapy.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis, bronchospasm, and swelling of the tongue and throat have been reported
  • Hypocalcemia - calcitonin may lower calcium levels. Severe hypocalcemia has been reported in some patients receiving calcitonin. Hypocalcemia should be corrected before treatment with calcitonin.
  • Adverse nasal reactions - nasal mucosal alterations may occur with prolonged use. Periodic nasal exam is recommended.
  • Malignancy - a meta-analysis of 21 randomized placebo-controlled trials found a higher incidence of malignancy in calcitonin-users when compared to placebo-users (4.1% vs 2.9%). A definitive causal relationship has not been established.
  • Calcitonin antibodies - antibodies to calcitonin may develop in some users. In a 2-year nasal spray study, 69% of patients treated with Miacalcin developed calcitonin antibodies compared to 3% of placebo-treated patients. It is unknown if antibody formation affects efficacy.
  • Vitamin D deficiency - treat if present to ensure proper mineral metabolism
  • Urine sediment - coarse granular casts and casts containing renal tubular epithelial cells have been reported in young healthy patients who were given injectable calcitonin and prescribed bed rest. Urine sediment abnormalities have not been reported in ambulatory patients.
  • Liver disease - has not been studied. Manufacturer makes no dosage recommendation.
  • Kidney disease - has not been studied. Manufacturer makes no dosage recommendation.

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Denosumab

(Prolia®)
Prolia® - injection
  • 60 mg/1 ml prefilled syringe
  • 60 mg/1 ml single-use vial
Osteoporosis and bone loss treatment
  • Dosing: 60 mg subcutaneously once every 6 months
  • Administer in the upper arm, the upper thigh, or the abdomen
  • All patients should receive calcium 1000 mg daily and at least 400 IU of vitamin D daily
  • If a dose is missed, administer as soon as available. Schedule next dose 6 months from date of last injection.
NO/$$$$

  • Store syringes and vials in a refrigerator

  • May allow syringes and vials to warm to room temperature before injecting

  • Syringes and vials are good for 14 days at room temperature. Do not expose to temperatures > 77°F.

  • Do not shake syringes or vials vigorously

  • Prolia is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles
Mechanism of action
  • Osteoclasts are cells that are responsible for bone resorption (see osteoporosis above)

  • RANKL is a protein that is essential for the formation, function, and survival of osteoclasts

  • Denosumab is a human IgG antibody that binds to RANKL. Denosumab inactivates RANKL thus preventing it from activating osteoclasts.

FDA-approved indications
  • Treatment of postmenopausal osteoporosis in women who are at high risk for fracture
  • Treatment of osteoporosis in men
  • Treatment of bone loss in women receiving adjuvant aromatase inhibitor therapy for breast cancer
In a large study detailed in the PI, no denosumab side effects occurred at an incidence ≥ 2% more than placebo
  • None known
  • Pregnancy - DO NOT USE. May cause fetal harm.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis, shortness of breath, swelling, and urticaria have been reported
  • Hypocalcemia - denosumab may lower calcium levels. The peak effect occurs 10 days after dosing. In one study, the average change in calcium levels 10 days after dosing was -5.5% in patients with CrCl < 30 ml/min, and -3.1% in patients with CrCl ≥ 30 ml/min. Patients at high risk for hypocalcemia (e.g. hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, kidney disease) should have their calcium and phosphorous levels checked within 14 days after an injection.
  • Osteonecrosis of the jaw (ONJ) - denosumab has been associated with ONJ. ONJ can occur spontaneously, but is generally associated with tooth extraction and/or local infection. Risk factors for ONJ include tooth extraction, dental implants, boney surgery, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, and ill-fitting dentures. A routine oral exam should be performed before administering denosumab. The risk of ONJ may increase with duration of exposure to denosumab.
  • Atypical femoral fractures - denosumab has been associated with a slight increase in risk for atypical subtrochanteric and diaphyseal femoral fractures. Concomitant corticosteroids may increase the risk. A prodromal phase of dull, aching thigh pain may precede the fracture for weeks to months.
  • Multiple vertebral fractures following discontinuation - after discontinuation of denosumab, fracture risk increases. In trials, 6% of women who discontinued denosumab developed new vertebral fractures, and 3% of women developed multiple vertebral fractures. The average time to onset of multiple vertebral fractures was 17 months (range 7 - 43 months) after the last injection. BMD returns to pretreatment values within 18 months after the last dose of denosumab. Consider starting another antiresorptive therapy upon discontinuation of denosumab.
  • Serious infections - RANKL receptors are present on the surface of activated T and B lymphocytes and in lymph nodes. Denosumab may affect the function of these cells and increase the risk of infection. In trials, the incidence of nonfatal serious infections was 4% in the denosumab group and 3.3% in the placebo group. Use caution in patients with immunodeficiencies.
  • Skin reactions - skin reactions including dermatitis, eczema, and rashes have been reported in denosumab users. In trials, 10.8% of patients in the denosumab group reported skin reactions compared to 8.2% in the placebo group.
  • Severe musculoskeletal pain - in rare cases, severe bone, muscle, and joint pain has been reported in patients taking denosumab. Time to onset of symptoms varied from days to months after starting the drug.
  • Denosumab antibodies - in trials lasting 5 years, less than 1% of patients developed antibodies to denosumab. Antibody production did not affect efficacy.
  • Kidney disease - no dose adjustment necessary. Patients with CrCl < 30 ml/min are at greater risk for hypocalcemia. Monitor closely.
  • Liver disease - has not been studied

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Raloxifene

(Evista®)
Evista® - tablet
  • 60 mg
Osteoporosis treatment and prevention in postmenopausal women
  • Dosing: 60 mg once daily

Reduction in the risk of breast cancer
YES/$$-$$$
(30 tablets)

  • May take without regard to food
Mechanism of action
  • Raloxifene is an estrogen agonist/antagonist, also referred to as a selective estrogen receptor modulator (SERM)
  • SERMs stimulate estrogen receptors in some tissues and block them in other tissues

    • Raloxifene has the following actions:
      • Bone
        • Osteoclast formation - neutral
        • Bone formation - agonist
        • Bone resorption - antagonist
      • Endometrium - neutral to partial agonist
      • Vagina - neutral
      • Breast - antagonist [9]

  • Stimulating estrogen receptors in bone leads to an increase in bone mineral density
  • Blocking estrogen receptors in breast tissue decreases the risk of breast cancer

FDA-approved indications
  • Treatment and prevention of osteoporosis in postmenopausal women
  • Reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis
  • Reduction in the risk of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer
NOTE: only side effects that occurred at an incidence of ≥ 2% and ≥ 1% more than placebo are listed

  • Joint pain - 15.5%, P - 14%
  • Flu syndrome - 13.5%, P - 11.4%
  • Hot flashes - 9.7%, P - 6.4%
  • Leg cramps - 7%, P - 3.7%
  • Uterine disorder - 3.3%, P - 2.3%
  • Cholestyramine - DO NOT COMBINE. Raloxifene absorption is reduced.
  • Warfarin - raloxifene may decrease the effectiveness of warfarin. Monitor PT/INR.
  • Highly protein-bound drugs - raloxifene is > 95% protein bound. It may theoretically interact with other highly protein-bound drugs (e.g. gemfibrozil, diazepam, diazoxide, lidocaine). In vitro, raloxifene did not interact with the binding of phenytoin, tamoxifen, or warfarin.
  • Estrogen - the safety of concomitant exogenous estrogens with raloxifene has not been evaluated and is not recommended
  • Childbearing potential - DO NOT USE in women who are pregnant or may become pregnant
  • Venous thromboembolism (VTE) - DO NOT USE. Raloxifene increases the risk of VTE and should not be used in women with a history of VTE. In the RUTH trial (median follow-up 5.6 years), there was an absolute increase in risk of VTE in the raloxifene group of 1.2 cases per 1000 woman-years when compared to the placebo group. [8]
  • Surgery and immobilization because of the increased risk of VTE, raloxifene should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g. surgery). Raloxifene should be resumed only when the patient is fully ambulatory.
  • Death due to stroke - in the RUTH trial (median follow-up 5.6 years), there was an increased risk of death due to stroke in the raloxifene group when compared to the placebo group (absolute risk increase, 0.7 cases per 1000 woman-years; hazard ratio 1.49; 95% CI, 1.00-2.24; p=0.0499). There was no statistically significant difference between the groups in the incidence of stroke. Risk/benefit should be considered when prescribing to women at increased risk of stroke. [8]
  • Premenopausal women - raloxifene has not been studied in premenopausal women and should not be used in these women
  • Effects on endometrium - raloxifene may cause a slight increase in endometrial thickness. In trials, placebo-treated women had a 0.27 mm mean decrease from baseline in endometrial thickness over 3 years, whereas the raloxifene-treated women had a 0.06 mm mean increase.
  • Endometrial polyps - in trials, histologically benign endometrial polyps were reported in 17 of 1999 placebo-treated women, 37 of 1948 Evista-treated women, and in 31 of 2010 women treated with raloxifene 120 mg/day.
  • Elevated triglycerides - estrogens and estrogen-like compounds may raise triglyceride levels. Monitor triglycerides in susceptible patients.
  • History of breast cancer - raloxifene has not been studied in women with a history of breast cancer
  • Unexplained uterine bleeding - unexplained uterine bleeding should be investigated as clinically indicated. In studies, raloxifene-treated and placebo-treated patients had similar incidences of endometrial proliferation.
  • Liver disease - clearance is decreased. Use caution.
  • Kidney disease
    • CrCl ≥ 60 ml/min: no dose adjustment necessary
    • CrCl < 60 ml/min: clearance is decreased. Use caution.

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Teriparatide

(Forteo®)
Forteo® - injection
  • Multi-dose pen containing 28 doses of 20 mcg
Osteoporosis treatment in men and women
  • Dosing: 20 mcg subcutaneously once daily
  • The safety of teriparatide has not been evaluated beyond a 2-year period. Use beyond 2 years is not recommended.

Glucocorticoid-induced osteoporosis
  • Dosing: 20 mcg subcutaneously once daily
  • The safety of teriparatide has not been evaluated beyond a 2-year period. Use beyond 2 years is not recommended.
NO/$$$$ (28 doses)

  • Keep pen refrigerated at all times

  • During the use period, time out of the refrigerator should be minimized. The dose may be delivered immediately following removal from the refrigerator.

  • Administer in thigh or abdominal wall

  • Teriparatide is a clear and colorless solution. Do not use if cloudy, colored, or particulate matter is present.
Mechanism of action
  • Teriparatide is a synthetic version of human parathyroid hormone (PTH). Teriparatide has an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone.
  • PTH regulates bone metabolism, and its actions are highly dependent upon the pattern of its exposure to bone. Intermittent, low-dose exposure to PTH stimulates bone development while long-term, sustained exposure stimulates bone resorption. The mechanism behind these differing effects is not completely understood.
  • The pattern of PTH exposure produced by teriparatide stimulates bone formation

FDA-approved indications
  • Treatment of postmenopausal women with osteoporosis at high risk for fracture
  • Increase of bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture
  • Treatment of men and women with glucocorticoid-induced osteoporosis at high risk for fracture
NOTE: only side effects that occurred at an incidence of ≥ 2% and ≥ 1% more than placebo are listed

  • Joint pain - 10.1%, P - 8.4%
  • Weakness - 8.7%, P - 6.8%
  • Nausea - 8.5%, P - 6.7%
  • Dizziness - 8%, P - 5.4%
  • Upset stomach - 5.2%, P - 4.1%
  • Depression - 4.1%, P - 2.7%
  • Vertigo - 3.8%, P - 2.7%
  • Shortness of breath - 3.6%, P - 2.6%
  • Leg cramps - 2.6%, P - 1.3%
  • Syncope - 2.6%, P - 1.4%
  • Digoxin - teriparatide may increase calcium levels. High calcium levels may increase the risk of digitalis toxicity. Use caution in patients taking digoxin.
  • Hydrochlorothiazide (HCTZ) - HCTZ may cause calcium retention in some patients. In studies, HCTZ 25 mg did not affect the serum calcium response to teriparatide 40 mcg. Effects of higher HCTZ doses are unknown.
  • Furosemide - loop diuretics like furosemide cause renal calcium excretion. Administration of teriparatide with furosemide resulted in small increases in the serum calcium (2%) and 24-hour urine calcium (37%) responses to teriparatide that did not appear to be clinically important.
  • Bone cancer and bone metastases - DO NOT USE
  • Metabolic bone disease (e.g. Paget's disease) - DO NOT USE
  • Hypercalcemia - DO NOT USE. Teriparatide may raise calcium levels and worsen hypercalcemia. In trials, the maximum effect of teriparatide on calcium levels was seen 4 - 6 hours post-dose. At 16 hours post-dose, levels were not different from baseline.
  • Hypercalcemic disorders - DO NOT USE in hypercalcemic disorders like primary hyperparathyroidism.
  • Osteosarcoma - in male and female rats, teriparatide caused an increased incidence of osteosarcoma. The effect was seen with exposures 3 - 60 times those seen in humans. Teriparatide should not be given to patients at increased risk of osteosarcoma. Risk factors for osteosarcoma include Paget's disease of bone; unexplained elevations of alkaline phosphatase; pediatric and young adult patients with open epiphyses; prior external beam or implant radiation therapy involving the skeleton.
  • Kidney stones (hypercalciuria) - teriparatide may increase renal calcium excretion. Use caution in patients with a history of calcium stones.
  • Orthostatic hypotension - in trials, transient episodes of orthostatic hypotension occurred in about 5% of patients during the first several doses. Typically, an event began within 4 hours of dosing and spontaneously resolved within a few minutes to a few hours.
  • Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported
  • Teriparatide antibodies - in trials, teriparatide antibodies developed in 3% of women. Antibody formation did not appear to affect serum calcium or efficacy.
  • Increase in uric acid - teriparatide may increase serum uric acid levels. Use caution in susceptible patients (e.g. gout).
  • Liver disease - has not been studied
  • Kidney disease
    • CrCl ≥ 30 ml/min: in single dose studies, no pharmacokinetic differences were observed
    • CrCl < 30 ml/min: clearance is decreased. Use caution.



  • PRICING

    • $ = 0 - $50
    • $$ = $51 - $100
    • $$$ = $101 - $150
    • $$$$ = > $151

    • Pricing based on one month of therapy at standard dosing in an adult
    • Pricing based on survey of GoodRX.com®, HEB®, and Costco®, [accessed 8/2015]
    • Pricing may vary by region and availability


  • References:

  • 1 - PMID 21224201 AACE OP GL
  • 2 - PMID 25182228 IOF GL
  • 3 - USPSTF website
  • 4 - PMID 22675062 Endocrine society recs in men
  • 5 - PMID 21083387 Bisphosphonates for OP
  • 6 - PMID 21542743 Femoral fx risk
  • 7 - PMID 20662044 ACR recs
  • 8 - PMID 16837676 Ruth trial
  • 9 - PMID 25423325 Ospemifene MOA
  • 10 - PMID 26420598 - Calcium intake and BMD
  • 11 - PMID 26420387 - Calcium intake and fracture risk