(eye BAN droh nate)
Treatment and prevention of osteoporosis in postmenopausal females
Hypersensitivity to ibandronate or any component of the formulation; hypocalcemia; oral tablets are also contraindicated in patients unable to stand or sit upright for at least 60 minutes and in patients with abnormalities of the esophagus which delay esophageal emptying, such as stricture or achalasia
Postmenopausal osteoporosis (treatment):Note: Consider discontinuing after 3-5 years of use for osteoporosis in patients at low-risk for fracture. Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
Oral: 150 mg once monthly
IV: 3 mg every 3 months
Postmenopausal osteoporosis (prevention): Oral: 150 mg once monthly. Note: Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
Hypercalcemia of malignancy (off-label use): IV: 2-6 mg over 1-2 hours (Pecherstorfer, 2003; Ralston, 1997)
Metastatic bone disease due to breast cancer (off-label use): IV: 6 mg every 3-4 weeks (Diel, 2004)
Missed doses:
Oral: If once-monthly oral dose is missed, it should be given the next morning after remembered if the next month 's scheduled dose is >7 days away. If the next month 's scheduled dose is within 7 days, wait until the next month 's scheduled dose. May then return to the original monthly schedule (original scheduled day of the month). Do not give >150 mg within 7 days.
IV: If an IV dose is missed, it should be administered as soon as it can be rescheduled. Thereafter, it should be given every 3 months from the date of the last injection.
Refer to adult dosing.
Osteoporosis: Oral, IV:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use not recommended.
Oncologic uses (off-label): IV: CrCl <30 mL/minute: 2 mg every 3-4 weeks (von Moos, 2005)
No dosage adjustment necessary (has not been studied); however, ibandronate does not undergo hepatic metabolism.
Oral: Administer 60 minutes before the first food or drink of the day (other than water) and prior to taking any oral medications or supplements (eg, calcium, antacids, vitamins). Ibandronate should be taken in an upright position with a full glass (6-8 oz) of plain water and the patient should avoid lying down for 60 minutes to minimize the possibility of GI side effects. Mineral water with a high calcium content should be avoided. The tablet should be swallowed whole; do not chew or suck. Do not eat or drink anything (except water) for 60 minutes following administration of ibandronate.
IV: Administer as a 15-30 second bolus intravenously; avoid paravenous or intraarterial administration (may cause tissue damage). Do not mix with calcium-containing solutions or other drugs. For osteoporosis, do not administer more frequently than every 3 months. Infuse over 1 hour for metastatic bone disease due to breast cancer (Diel, 2004) and over 1-2 hours for hypercalcemia of malignancy (Pecherstorfer, 2003; Ralston, 1997).
Ensure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Women and men should consume:
Calcium: 1,000 mg/day (men: 50 to 70 years) or 1,200 mg/day (women ≥51 years and men ≥71 years) (IOM, 2011; NOF [Cosman 2014])
Vitamin D: 800 to 1,000 int. units daily (men and women ≥50 years) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 int. units daily (men and women ≤70 years) or 800 int. units daily (men and women ≥71 years) (IOM, 2011).
Ibandronate tablet should be taken with a full glass (6 to 8 oz) of plain water, at least 60 minutes prior to any food, beverages, or medications. Mineral water with a high calcium content should be avoided.
Store at controlled room temperature of 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Boniva: 3 mg/3 mL (3 mL)
Generic: 3 mg/3 mL (3 mL)
Solution, Intravenous [preservative free]:
Generic: 3 mg/3 mL (3 mL)
Tablet, Oral:
Boniva: 150 mg
Generic: 150 mg
Aminoglycosides: May enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy
Antacids: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of antacids containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Magaldrate; Sodium Bicarbonate. Consider therapy modification
Calcium Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral calcium supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Deferasirox: Bisphosphonate Derivatives may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Iron Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral iron supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification
Magnesium Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral magnesium salts within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Bisphosphonate Derivatives. Specifically, polyvalent cation-containing multivitamins may decrease the absorption of orally-administered bisphosphonate derivatives. Management: Avoid administration of polyvalent cation-containing multivitamins within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Bisphosphonate Derivatives. Specifically, polyvalent cation-containing multivitamins may decrease the absorption of orally-administered bisphosphonate derivatives. Management: Avoid administration of polyvalent cation-containing multivitamins within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Monitor therapy
Proton Pump Inhibitors: May diminish the therapeutic effect of Bisphosphonate Derivatives. Monitor therapy
Systemic Angiogenesis Inhibitors: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Monitor therapy
Osteoporosis: Bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 2 years thereafter (NOF [Cosman 2014]); annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; may consider measuring biochemical markers of bone turnover
Serum creatinine prior to each IV dose
Bisphosphonates may interfere with diagnostic imaging agents such as technetium-99m-diphosphonate in bone scans.
Percentages vary based on frequency of administration (daily vs monthly). Unless specified, percentages are reported with oral use.
>10%:
Gastrointestinal: Dyspepsia (4% to 12%)
Neuromuscular & skeletal: Back pain (4% to 14%)
Respiratory: Upper respiratory tract infection (2% to 34%)
1% to 10%:
Cardiovascular: Hypertension (6% to 7%)
Central nervous system: Headache (3% to 7%), dizziness (1% to 4%), fatigue (3%), insomnia (1% to 2%), depression (2%)
Dermatologic: Skin rash (1% to 2%)
Gastrointestinal: Abdominal pain (5% to 8%), diarrhea (2% to 7%), nausea (4% to 5%), dental disease (4%), constipation (3% to 4%), vomiting (3%), gastritis (2%), gastroenteritis (3%)
Genitourinary: Urinary tract infection (2% to 6%), cystitis (3%)
Hypersensitivity: Acute phase reaction-like symptoms (IV: 10%; oral: 3% to 9%), hypersensitivity reaction (3%)
Infection: Influenza (4% to 8%)
Local: Injection site reaction (<2%)
Neuromuscular & skeletal: Limb pain (1% to 8%), arthralgia (4% to 9%), myalgia (1% to 6%), arthropathy (4%), weakness (4%), localized osteoarthritis (1% to 3%), muscle cramps (2%)
Respiratory: Bronchitis (3% to 10%), pneumonia (6%), nasopharyngitis (3% to 4%), flu-like symptoms (1% to 3%), pharyngitis (3%)
Postmarketing and/or case reports (Limited to important or life-threatening): Acute renal failure, anaphylactic shock, anaphylaxis, angioedema, bullous dermatitis, erythema multiforme, exacerbation of asthma, femur fracture (diaphyseal or subtrochanteric), hypocalcemia, iritis, musculoskeletal pain (bone, joint, or muscle; incapacitating), ophthalmic inflammation, osteonecrosis of the jaw, prolonged Q-T interval on ECG (Bonilla 2014), scleritis, Stevens-Johnson syndrome, uveitis
Patients with CrCl 40-70 mL/minute had 55% higher AUC and patients with CrCl 30 mL/minute had more than a 2-fold increase in exposure.
Progressive age-related changes in renal function may alter the elimination of ibandronate in elderly patients.
Concerns related to adverse effects:
- Bone fractures: Atypical femur fractures have been reported in patients receiving bisphosphonates for treatment/prevention of osteoporosis. The fractures include subtrochanteric femur (bone just below the hip joint) and diaphyseal femur (long segment of the thigh bone). Some patients experience prodromal pain weeks or months before the fracture occurs. It is unclear if bisphosphonate therapy is the cause for these fractures, although the majority of cases have been reported in patients taking bisphosphonates. Patients receiving long-term (>3-5 years) therapy may be at an increased risk. Discontinue bisphosphonate therapy in patients who develop a femoral shaft fracture.
- Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Discontinue intravenous ibandronate therapy in patients who experience severe symptoms; symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy.
- Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, dysphagia, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Discontinue if new or worsening symptoms develop.
- Hypocalcemia: Hypocalcemia has been reported with the use of bisphosphonates. Prior to therapy initiation, hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake.
- Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients receiving bisphosphonates. Known risk factors for MRONJ include invasive dental procedures (eg, tooth extraction, dental implants, boney surgery), cancer diagnosis, concomitant therapy (eg, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, ill-fitting dentures, and comorbid disorders (anemia, coagulopathy, infection, preexisting dental or periodontal disease). Risk may increase with increased duration of bisphosphonate use. According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonates and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy; risk is significantly higher in cancer patients receiving antiresorptive therapy compared to patients receiving osteoporosis treatment (regardless of medication used or dosing schedule). MRONJ risk is also increased with monthly IV antiresorptive therapy compared to the minimal risk associated with oral bisphosphonate use, although risk appears to increase with oral bisphosphonates when duration of therapy exceeds 4 years (AAOMS [Ruggiero 2014]). The manufacturer 's labeling states that discontinuing bisphosphonates in patients requiring invasive dental procedures may reduce the risk of ONJ and clinical judgment by physician and/or oral surgeon should be used. However, the AAOMS suggests there is currently no evidence that interrupting oral bisphosphonate therapy alters the risk of ONJ following tooth extraction, and that no alternations or delay in any procedure common to oral/maxillofacial surgeons, periodontists, and other dental providers is necessary in patients receiving oral bisphosphonates for <4 years who have no clinical risk factors (special considerations apply to patients receiving dental implants). Conversely, in patients receiving oral bisphosphonates for >4 years or in patients receiving oral bisphosphonates for <4 years who have also taken corticosteroids or antiangiogenic medications concomitantly, the AAOMS recommends considering a 2-month drug free period prior to invasive dental procedures based on a theoretical benefit. Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]). According to the manufacturer, discontinuation of oral bisphosphonate therapy should be considered (based on risk/benefit evaluation) in patients who develop ONJ.
Disease-related concerns:
- Renal impairment: Use not recommended with severe renal impairment (CrCl <30 mL/minute).
Dosage form specific issues:
- Injection: Intravenous bisphosphonates may cause transient decreases in serum calcium and have also been associated with renal toxicity.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Duration of therapy: In the management of osteoporosis, re-evaluate the need for continued therapy periodically; the optimal duration of treatment has not yet been determined. Consider discontinuing after 3-5 years of use in patients at low-risk for fracture; following discontinuation, re-evaluate fracture risk periodically.
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Adverse effects were observed in animal reproduction studies. It is not known if bisphosphonates cross the placenta, but fetal exposure is expected (Djokanovic, 2008; Stathopoulos, 2011). Bisphosphonates are incorporated into the bone matrix and gradually released over time. The amount available in the systemic circulation varies by dose and duration of therapy. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy; however, available data have not shown that exposure to bisphosphonates during pregnancy significantly increases the risk of adverse fetal events (Djokanovic, 2008; Levy, 2009; Stathopoulos, 2011). Until additional data is available, most sources recommend discontinuing bisphosphonate therapy in women of reproductive potential as early as possible prior to a planned pregnancy; use in premenopausal women should be reserved for special circumstances when rapid bone loss is occurring (Bhalla, 2010; Pereira, 2012; Stathopoulos, 2011). Because hypocalcemia has been described following in utero bisphosphonate exposure, exposed infants should be monitored for hypocalcemia after birth (Djokanovic, 2008; Stathopoulos, 2011).
A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density.
Terminal Vd: 90 L; 40% to 50% of circulating ibandronate binds to bone
Not metabolized
Urine (50% to 60% of absorbed dose, excreted as unchanged drug); feces (unabsorbed drug)
Oral: 0.5-2 hours
Oral: 150 mg dose: Terminal: 37-157 hours
IV: Terminal: ¢ ˆ ¼5-25 hours
85.7% to 99.5%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, diarrhea, flu-like symptoms, back pain, painful extremities, or injection site pain or irritation. Have patient report immediately to prescriber signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures); signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain); eye pain; vision changes; severe abdominal pain; severe bone pain; severe muscle pain; severe joint pain; groin, hip, or back pain; severe dizziness; severe headache; jaw pain or edema; angina; heartburn; black, tarry, or bloody stools; coughing up blood; vomiting blood; dysphagia; pain with swallowing; or mouth sores (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.