Boniva

Injectable Bisphosphonates
Oral Bisphosphonates

Administer in the morning with a full glass of plain water (180 to 240 mL or 6 to 8 ounces) at least 1 hour before the first food, beverage, or medication of the day. Administering on an empty stomach is critical to drug effectiveness and the avoidance of selected side effects. At least 1 hour should elapse after an ibandronate dose before administering any other oral drugs.
To avoid esophageal irritation, the patient should not lie down for at least 1 hour after administering the dose. Do not administer at bedtime or before arising.
Ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use the prefilled syringe if particulate matter or discoloration is present.
Take precautions to prevent allergic reactions by ensuring appropriate monitoring and medical support are available during administration.
Ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia.

Intravenous ibandronate must be administered by a health care professional.
Ibandronate is administered every 3 months; do not give more often than every 3 months.
Ibandronate is available in 3 mg/3 mL prefilled syringes. The prefilled syringes are for single use only; discard unused portion. Use the needle provided by the manufacturer for drug administration.
Administer via IV injection only. Do not administer by another route, especially intraarterially or paravenously, as this could lead to tissue damage.
Do not mix the injection with calcium-containing solutions or other intravenously administered drugs.
Administer IV over 15 to 30 seconds.[31826]

uveitis / Delayed / 0-0.1
atrial fibrillation / Early / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
esophageal ulceration / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
esophageal stricture / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
visual impairment / Early / Incidence not known
osteonecrosis / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known

hypertension / Early / 5.3-7.3
hypercholesterolemia / Delayed / 1.5-4.8
constipation / Delayed / 2.5-4.1
cystitis / Delayed / 3.4-3.4
erythema / Early / 1.3-2.8
gastritis / Delayed / 1.9-2.2
depression / Delayed / 1.3-2.2
hot flashes / Early / Incidence not known
dysphagia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
melena / Delayed / Incidence not known
bone pain / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
ocular inflammation / Early / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
hypercalciuria / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hypophosphatemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known

arthralgia / Delayed / 3.5-14.0
back pain / Delayed / 4.3-13.5
dyspepsia / Early / 3.6-11.9
fever / Early / 1.1-10.0
abdominal pain / Early / 5.1-7.8
diarrhea / Early / 2.4-6.8
headache / Early / 2.6-6.5
myalgia / Early / 0.8-5.7
nausea / Early / 2.1-5.1
pharyngitis / Delayed / 2.5-4.3
infection / Delayed / 4.3-4.3
dizziness / Early / 1.0-3.7
asthenia / Delayed / 3.5-3.5
vertigo / Early / 3.0-3.0
pruritus / Rapid / 1.3-2.8
rash / Early / 1.3-2.8
maculopapular rash / Early / 1.3-2.8
vomiting / Early / 2.7-2.7
insomnia / Early / 0.8-2.6
injection site reaction / Rapid / 0-2.0
muscle cramps / Delayed / 1.8-2.0
diaphoresis / Early / Incidence not known
pyrosis (heartburn) / Early / Incidence not known
dysgeusia / Early / Incidence not known
gastroesophageal reflux / Delayed / Incidence not known
musculoskeletal pain / Early / Incidence not known
ocular pain / Early / Incidence not known

Boniva

Rx

Potent oral and parenteral third-generation bisphosphonate
Primarily used for treatment and prevention of postmenopausal osteoporosis; increases bone mineral density and reduces vertebral fracture risk; consider if spine-specific osteoporosis therapy needed
Used off-label for hypercalcemia of malignancy and for reduction of skeletal events in patients with breast cancer and bone metastases

150 mg PO once monthly on the same date each month. Supplement with calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Once per month dosing has similar clinical effects when compared to the previously available 2.5 mg/day dosing regimen.[27859] Continue an oral bisphosphonate for up to 10 years in postmenopausal women who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk postmenopausal women. For those patients at low or moderate risk for fracture, consider stopping ibandronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Ibandronate may be an appropriate initial treatment choice for postmenopausal women requiring spine-specific efficacy.

3 mg IV (over 15 to 30 seconds) every 3 months. Do not administer more often than every 3 months. Supplement with calcium and vitamin D if dietary intake is inadequate. If a dose is missed, administer the missed dose as soon as possible and schedule future injections every 3 months from that date. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Continue an oral bisphosphonate for up to 10 years in postmenopausal women who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk postmenopausal women. For those patients at low or moderate risk for fracture, consider stopping ibandronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Ibandronate may be an appropriate initial treatment choice for postmenopausal women requiring spine-specific efficacy.

150 mg PO once monthly on the same date each month. Supplement with calcium and vitamin D if dietary intake is inadequate. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.

Safety and efficacy have not been established; oral therapy is preferred by expert guidelines. Various dose regimens have been used in trials. 2 mg given IV once every 3 months has been found effective for up to 2 years.

150 mg PO once monthly on the same date each month. Supplement with calcium and vitamin D if intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping ibandronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Use of bisphosphonates to prevent bone loss can be considered in postmenopausal women with low bone mineral density (T-score less than -1) and other risk factors for fracture who do not meet criteria for osteoporosis treatment.

150 mg PO once monthly on the same date each month. Supplement with calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping ibandronate after 3 to 5 years. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.

Safety and efficacy have not been established; ibandronate has only been studied for short-term control of Paget's disease. Single doses of 2 mg IV (over 15 to 30 seconds) or as a 6 mg IV infusion have been reported. No long-term clinical trials exist. Guidelines recommend other bisphosphonates (e.g., zoledronic acid) preferentially for Paget's disease due to long-term data with those medications at reducing pain and lytic lesions and improving quality of life.

Safety and efficacy have not been established; limited data reports in literature. In one comparator study, patients (n = 72) received ibandronate 2 mg or 4 mg as an IV infusion given over 2 hours or a pamidronate IV infusion (15 to 90 mg), with dosage of each agent was chosen according to the baseline degree of hypercalcemia. The most common dosage of ibandronate was a 4 mg IV infusion. Ibandronate and pamidronate resulted in similar efficacy and tolerability.

50 mg PO once daily; this dosage is approved in Europe. This dosage form is not available in the U.S. Efficacy in reducing fracture rates (vertebral and non-vertebral) and bone pain was demonstrated in breast cancer patients.

6 mg IV infusion (over at least 15 minutes, and longer if renal impairment is present) given every 3 to 4 weeks. This dosage is approved in Europe. This dosage form is not available in the U.S. Efficacy in reducing fracture rates (vertebral and non-vertebral) and bone pain was demonstrated in breast cancer patients.

†Indicates off-label use

No dosage adjustment required.

CrCl 30 mL/minute or more: Dosage adjustments are not necessary.
CrCl less than 30 mL/minute: Use not recommended.
For off-label indications and dosage forms, different renal dosing and administration recommendations apply.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aluminum Hydroxide: (Moderate) Separate administration of oral ibandronate and aluminum hydroxide by at least 1 hour. Aluminum-containing antacids will interfere with the absorption of oral ibandronate.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of oral ibandronate and aluminum hydroxide by at least 1 hour. Aluminum-containing antacids will interfere with the absorption of oral ibandronate.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate administration of oral ibandronate and aluminum hydroxide by at least 1 hour. Aluminum-containing antacids will interfere with the absorption of oral ibandronate.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of oral ibandronate and aluminum hydroxide by at least 1 hour. Aluminum-containing antacids will interfere with the absorption of oral ibandronate.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of oral ibandronate and aluminum hydroxide by at least 1 hour. Aluminum-containing antacids will interfere with the absorption of oral ibandronate.
Amikacin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Aminoglycosides: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Aspirin, ASA: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients. (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Omeprazole: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Oxycodone: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Bumetanide: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate use, respectively, and aspirin. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Calcium (oral): (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium Acetate: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium Carbonate: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium Carbonate; Simethicone: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium Gluconate: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Calcium; Vitamin D: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Chromium: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Cyclosporine: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like cyclosporine may increase the risk of developing nephrotoxicity.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including ibandronate.
Ethacrynic Acid: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Folic Acid, Vitamin B9: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Food: (Major) Ibandronate oral absorption becomes almost negligible if ibandronate is taken within 2 hours of breakfast. Even orange juice or coffee can reduce bioavailability. The ingestion of high-calcium foods can interfere with the absorption of ibandronate, and should not be eaten before or for at least 60 minutes after, administration of ibandronate. To achieve maximum possible bioavailability, ibandronate must be taken in the fasting state and at least 2 hours before a standard breakfast.
Furosemide: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Gentamicin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Iron: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
Lanthanum Carbonate: (Moderate) To limit absorption problems, the oral bisphosphonates should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like the oral bisphosphonates, may also be bound by lanthanum carbonate. Separating times of administration will maximize absorption and clinical benefit of the bisphosphonate. Separate the times of administration appropriately. Monitor the patient's clinical status and bone density as recommended to ensure the appropriate response to bisphosphonate therapy is obtained.
Loop diuretics: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Magnesium Citrate: (Moderate) Do not administer oral magnesium-containing products within 2 hours of oral bisphosphonates; oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g., alendronate, etidronate, ibandronate, risedronate, or tiludronate). All medications should be administered at least 30 minutes after an alendronate or risedronate dose, and at least 1 hour after an ibandronate dose to help prevent absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after these drugs or at a different time of day.
Magnesium Salts: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day.
Magnesium: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day.
Non-Ionic Contrast Media: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate, respectively, and nonsteroidal antiinflammatory drugs. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Omeprazole; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Paromomycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Plazomicin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Polycarbophil: (Moderate) Coadministration of ibandronate with calcium polycarbophil can interfere with the oral absorption of ibandronate; do not administer calcium polycarbophil within 60 minutes of ibandronate. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
Pyridoxine, Vitamin B6: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day.
Streptomycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Tacrolimus: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like tacrolimus may increase the risk of developing nephrotoxicity.
Tobramycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Torsemide: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Vancomycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like vancomycin may increase the risk of developing nephrotoxicity.

Boniva/Ibandronate Sodium Intravenous Inj Sol: 3mg, 3mL
Boniva/Ibandronate Sodium Oral Tab: 150mg

2.5 mg/day PO, 150 mg/month PO, or 3 mg IV every 3 months for osteoporosis-related indications; for selected off-label indications, doses as large as 50 mg/day PO or 6 mg IV infusion as a single dose have been used.

2.5 mg/day PO, 150 mg/month PO, or 3 mg IV every 3 months for osteoporosis-related indications; for selected off-label indications, doses as large as 50 mg/day PO or 6 mg IV infusion as a single dose have been used.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Ibandronate has pharmacologic actions similar to those of other bisphosphonates, although, compared to other bisphosphonates, ibandronate is more potent than alendronate, pamidronate, and clodronate, but is less potent than risedronate. Bone resorption releases excessive amounts of calcium into the blood. The double phosphonate group common to all bisphosphonates allows them to bind to calcified bone matrix. Adsorption of ibandronate to hydroxyapatite crystals in the mineralized matrix reduces solubility of the matrix and therefore osteoclastic resorption. A stable bone matrix will also prevent signaling to osteoclasts to migrate to the site. Ibandronate blocks attachment of osteoclast precursors to mineralized matrix, preventing transformation into mature, functioning osteoclasts. Ibandronate reduces bone turnover and, when used in combination with adequate hydration to increase renal excretion of calcium, reduces serum calcium concentrations. Serum calcium concentrations, urinary calcium/creatinine ratio, and hydroxyproline/creatinine ratio usually return to within or below normal within the first week after treatment.
 
In multiple myeloma, myeloma cells release soluble factors that activate osteoclasts to resorb bone. In multiple myeloma animal models, ibandronate inhibited osteoclast stimulatory activity and the development of lytic lesions, but not eventual tumor burden. Inhibition of enzymes in the mevalonate pathway appears to explain the effectiveness of ibandronate in multiple myeloma. It is expected that, like other bisphosphonates, ibandronate decreases the extent of accelerated bone resorption that results from osteoclast hyperactivity. Hypercalcemia is a common problem affecting cancer patients. Malignancy-associated hypercalcemia arises from accelerated bone resorption. This form of hypercalcemia could result from a direct skeletal action by various tumors inducing osteoclast hyperactivity. Ibandronate does not lower the level of parathyroid hormone-related protein (PTHrP) in patients with hypercalcemia of malignancy. Ibandronate inhibits bone resorption without inhibiting bone formation or mineralization. The drug has no antineoplastic properties.
 
Like other bisphosphonates, the exact mechanism of ibandronate's therapeutic effect in patients with Paget's disease has not been clearly established. Paget's disease is a progressive, idiopathic disease of bone. Increasing numbers of unusually large osteoclasts are produced at affected sites. Increased bone resorption follows, which is compensated for by an increase in new bone formation. This new bone is inferior and often deformed, and can fracture easily. Bisphosphonates are believed to reduce the solubility of mineralized bone matrix by adsorption to hydroxyapatite crystals in the matrix. The matrix becomes less soluble and resistant to osteoclastic resorption. Ibandronate, and other bisphosphonates, can also block the formation of mature osteoclasts by affecting the attachment of osteoclast precursors to the mineralized matrix.

Ibandronate is administered orally and intravenously.  After absorption, it is rapidly redistributed to bone or undergoes urinary excretion. Ibandronate is 86—99% bound to protein in human plasma; an estimated 40—50% of the circulating dose is bound to the bone. There is no evidence that any metabolism takes place. The portion that is not removed from the circulation via bone absorption is eliminated unchanged by the kidney (approximately 50—60% of the absorbed dose). Any unabsorbed orally-administered ibandronate is eliminated unchanged in the feces. The apparent half-life range is broad, generally 5—60 hours, and dependent on the dosage studied and on assay sensitivity. However, early plasma concentrations fall quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration, respectively.
 
Affected cytochrome P450 isoenzymes: none

With oral administration, ibandronate is absorbed in the upper gastrointestinal tract. Oral absorption is poor, with a bioavailability of approximately 0.6% compared to intravenous dosing. Absorption becomes almost negligible if ibandronate is taken within 1 hour of breakfast. To achieve maximum possible bioavailability, ibandronate must be taken in the fasting state and at least 1 hour before a standard breakfast. Concomitantly administered cations (e.g., calcium, magnesium) are likely to reduce bioavailability. After an oral dose, the time to maximum observed plasma ibandronate concentrations (Cmax) ranged from 0.5 to 2 hours (median 1 hour) in fasted healthy postmenopausal women.

Ibandronate is not indicated for use in women of reproductive potential. There are no data of ibandronate use during human pregnancy to inform of any drug-associated risks. Based on animal studies and the known class effects of bisphosphonates, fetal harm may occur. Reproductive studies in animals indicate that ibandronate may be associated with increased incidence of fetal renal pelvis ureter (RPU) syndrome, impaired infant neuromuscular development, maternal hypocalcemia, postimplantation fetal loss, dystocia and maternal periparturient death, and maternal and fetal death.

Ibandronate is not indicated in women of reproductive potential; use during breast-feeding is not recommended due to the potential for serious adverse events in a breastfed infant. There are no data on the presence of ibandronate in human milk, the effects on the breastfed infant, or the effects on milk production. Ibandronate was excreted into the milk of lactating rats after intravenous administration and remained present in rat breast milk for 2 to 24 hours after dose administration; the milk concentration averaged 1.5 times plasma concentrations.