Ibandronate is a potent oral and parenteral third-generation bisphosphonate. Oral daily and monthly regimens, and every 3 month intravenous regimens have been used, but how the drug is administered varies widely with the indication for use. Treatment with ibandronate is associated with significant increases in bone mineral density (BMD) and reduces the risk for radiographic vertebral fractures in patients with osteoporosis. Bisphosphonates are generally considered to be first-line therapy for the treatment of postmenopausal osteoporosis. However, ibandronate is not considered the first line bisphosphonate choice per osteoporosis treatment guidelines since evidence is insufficient to determine the effect of ibandronate on nonvertebral fractures (e.g., hip fractures); experts state ibandronate may be considered initially for patients requiring spine-specific osteoporosis therapy. For osteoporosis prevention, the second and third-generation bisphosphonates appear to offer similar benefits across the class to increase bone mineral density; the balance of costs, benefits, and harms of treating osteopenic patients with bisphosphonates is most favorable when the estimated risk for fracture is high. Ibandronate is under investigation for the management Paget's disease; ibandronate has been shown to provide effective short-term control of Paget's disease, but long-term studies are lacking; guidelines for Paget's disease preferentially recommend other potent bisphosphonates for this indication. Ibandronate has been investigated for the prevention and treatment of osteoporosis in patients receiving chronic corticosteroid treatment; evidence of sufficient quality is not yet available for this population. Ibandronate, as with other bisphosphonates, has been studied in the treatment of hypercalcemia of malignancy. In patients with breast cancer and bone metastases, the drug has been approved in Europe for the prevention of adverse skeletal events, but the drug is not approved in the U.S. for this indication. As with other bisphosphonates, the drug may also be useful in other cancer patients with osteopenia to help reduce the risk for skeletal events, but more study is needed. Ibandronate was first approved by the FDA in 2003.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-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.
Injectable Administration
-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 Administration
-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.
During clinical trials of oral ibandronate once daily for osteoporosis in postmenopausal women, most adverse events were mild or moderate and did not lead to discontinuation. Furthermore, in a 1-year, double-blind study comparing ibandronate IV to oral ibandronate, the overall safety profiles of the 2 dosage regimens were similar. During clinical investigations of oral daily ibandronate, the incidence of serious adverse events was 20% in the placebo group and 23% in the ibandronate group. The percentage of patients who withdrew from treatment due to adverse events was approximately 17% in both the ibandronate and placebo groups, with adverse events of the digestive system being the most common reason for withdrawal. The once monthly administration of oral ibandronate has a similar safety and tolerability profile in postmenopausal women, compared to once daily administration. In a 1-year, double-blind study comparing once daily (2.5 mg) to once monthly (150 mg) ibandronate, the incidence of serious adverse events was 4.8% in the daily group compared with 7.1% in the monthly group. The percentage of patients who withdrew from treatment due to adverse events was 8.9% in the daily group versus 7.8% in the monthly group.
Conflicting data exists regarding the use of bisphosphonates and an increased risk of serious atrial fibrillation. Atrial fibrillation is not specifically reported in the pre-marketing studies of ibandronate. At this time; the FDA has not identified a causal relationship between bisphosphonate use and a risk of atrial fibrillation. In the HORIZON Pivotal Fracture Trial, the incidence of serious atrial fibrillation (life-threatening or resulting in hospitalization or disability) was significantly higher in patients receiving zoledronic acid than placebo (50 patients or 1.3% versus 20 patients or 0.5%, p < 0.001), although the incidence of any atrial fibrillation (serious and non-serious) was not different between the 2 groups. Similarly, in a re-analysis of the Fracture Intervention Trial, patients taking alendronate also experienced a trend towards a higher incidence of serious atrial fibrillation versus those taking placebo (47 patients or 1.5% vs. 31 patients or 1%, HR 1.51, 95% CI 0.97-2.40, p=0.07). Similar to the HORIZON trial, any atrial fibrillation was not higher in patients taking alendronate. Post-marketing surveillance of reports of atrial fibrillation in patients receiving oral and intravenous bisphosphonates has not revealed a subset of patients at risk for the adverse effect. In the majority of cases in patients who received zoledronic acid, atrial fibrillation occurred more than 1 month after drug infusion. In order to review the potential risk of atrial fibrillation in patients receiving bisphosphonates, the FDA requested placebo-controlled clinical trial data from manufacturers. Information submitted to the FDA by the 4 manufacturers included data from 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed up for 6 months-3 years. After reviewing these data, the FDA concluded that most studies contained 2 or fewer events of atrial fibrillation. The absolute difference in event rates between each of the bisphosphonate and placebo arms varied from 0-3 per 1,000. No association between bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was found. In addition, an increase in dose or duration of bisphosphonate therapy did not correlate with an increased rate of atrial fibrillation. Because of the conflicting data in the literature, the FDA is exploring the feasibility of conducting additional epidemiologic studies to gather more data. The FDA continues to monitor post-marketing reports of atrial fibrillation in patients who have taken bisphosphonates. Currently, the FDA does not recommend a change in prescribing practices for this class of drugs; a causal relationship has not been identified.
Although the degree of change in blood pressure was not reported, hypertension has been noted in pre-marketing clinical trials of ibandronate. In separate clinical trials, hypertension occurred in 7.1% to 7.3% of study patients receiving daily oral ibandronate, 6.3% of study patients receiving monthly oral ibandronate, and 5.3% of those receiving quarterly parenteral ibandronate.
Hypersensitivity and hypersensitivity-like reactions have occurred. During clinical trials, allergic reaction (undefined) was reported in 2.5% of ibandronate-treated patients and in 1.9% of placebo-treated patients. In addition, rash (unspecified) was reported in 1.3% of study patients taking monthly, and 2.3% of patients taking daily, oral ibandronate and in separate study, in 2.8% of those on oral vs. 2.3% of patients on parenteral ibandronate. For these studies, rash included: rash, rash pruritic (rash with pruritus), rash macular or rash papular (maculopapular rash), dermatitis, dermatitis allergic, exanthem, erythema, rash generalized, dermatitis medicamentosa, and rash erythematous. Allergic reactions including fatal cases of anaphylaxis (anaphylactic shock), angioedema, asthma exacerbation, bronchospasm, Stevens-Johnson syndrome, erythema multiforme, dermatitis bullous, and rash have been reported in post-marketing experience with ibandronate.
Injection site reaction such as erythema, redness, or swelling are infrequently observed with intravenous ibandronate (< 2% with ibandronate vs < 1% with placebo). In most cases, the reaction is mild to moderate in severity. Acute-phase reactions (APR), which may include fever, are more common in the IV ibandronate group as compared to oral ibandronate (10% for IV, 9% monthly PO, and 4% daily PO); incidence is also higher in IV as compared to PO treated patients when considering the combination of APR and influenza-like illness (4% for IV vs 1.1% for daily PO). The incidence of APR is based on reporting of any of 33 potential APR-like symptoms within 3 days of an IV dose and for a duration <= 7 days. In most cases, no specific treatment is required and the symptoms subside within 24-48 hours. Other symptoms commonly reported with IV ibandronate include diaphoresis and hot flashes.
Adverse events of the digestive system were reportedly the most common reason for withdrawal from clinical trials of orally administered ibandronate and often among the most common adverse events reported in clinical trials of any form of ibandronate. Careful administration instruction counseling by health care providers and adherence by patients may minimize risk. In separate clinical trials of ibandronate for postmenopausal osteoporosis, dyspepsia has been reported during therapy with placebo (9.8%), daily oral ibandronate (4.3% to 11.9%), monthly oral ibandronate (5.6%), and with parenteral ibandronate (3.6%). In addition to dyspepsia, other reported adverse events included: abdominal pain (5% placebo, 5.6-6% daily oral ibandronate, 7.8% monthly oral ibandronate, 5.1% quarterly parenteral ibandronate), constipation (not reported, 2.5-4.1%, 4%, 3.4%), diarrhea (5%, 2.4-6.8%, 5.1%, 2.8%), gastritis (1.9%, 2.2%, not reported, 1.9%), pharyngitis or nasopharyngitis (1.5%, 2.5-4.3%, 3.5%, 3.4%), and nausea (not reported, 4.3-4.8%, 5.1%, 2.1%) vomiting (2.1%, 2.7%, not reported, not reported). Although not specifically reported in ibandronate trials, dysgeusia, dysphagia, esophageal ulceration, esophageal stricture, esophagitis, gastroesophageal reflux, GI bleeding, GI perforation, melena, oral ulceration, peptic ulcer, and pyrosis (heartburn) have been reported in patients receiving therapy with bisphosphonates. During the pre-marketing study of oral ibandronate, patients with active GI disease were excluded; however, those with previous history of gastrointestinal disease, such as peptic ulcers without recent bleeding or hospitalization, dyspepsia, and reflux controlled by medication, were included. Furthermore, during clinical studies of ibandronate either once daily or monthly, approximately 15% of patients were taking either an H2 blocker or proton pump inhibitor.
Arthralgia (14% with placebo, 3.5-14% with daily oral ibandronate, 5.6% with monthly oral ibandronate, and 9.6% with quarterly parenteral ibandronate), joint disorder (3.3%, 3.6%, not stated, not stated), myalgia (5.1%, 0.8-5.7%, 2%, 2.8%), arthritis or localized osteoarthritis (2.7%, 1.3-3.2%, 3%, 1.5%), back pain (12.2%, 4.3-13.5%, 4.5%, 7%), pain in extremity (6.4%, 1.3-7.8%, 4%, 2.8%), muscle cramps (not stated, 2%, 1.8%, not stated), bone pain (incidences not stated), and musculoskeletal pain (incidences not stated) have been reported during clinical trials and/or post-marketing surveillance. The bone, muscle, and/or joint pain can sometimes be severe and even incapacitating. Pain, particularly dull or achy pain, of the thigh or groin may occur as a prodrome to atypical fracture of the femur; prompt evaluation to rule out incomplete fracture is strongly recommended. The time to onset of symptoms varies from one day to several months after drug initiation. Most patients have relief of symptoms after stopping the medication; a subset of patients have had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate. Risk factors for and the incidence of bone, muscle, and/or joint pain are not known. This reaction is different than the acute phase reaction of fever, chills, and bone, muscle, and/or joint pain that accompanies intermittent intravenous or weekly or monthly oral bisphosphonates. The acute phase reaction tends to resolve with continued use. Bisphosphonates should be considered as a cause for any patient who presents with severe musculoskeletal or joint pain; furthermore, if ibandronate is determined to be the cause, temporary or permanent discontinuation in drug therapy should be considered.
Nervous system and psychiatric adverse events reported in pre-marketing clinical trials with ibandronate include: dizziness (2.6% placebo, 1-3.7% daily oral ibandronate, 2.3% monthly oral ibandronate, 1.9% quarterly parenteral ibandronate) and headache (5.8%, 2.6-6.5%, 3.3%, 3.6%). Asthenia (3.5% with ibandronate vs 2.3% with placebo), nerve root lesion (2.2% vs 1.9%), and vertigo (3% vs 2.5%) were reported only during study comparing oral ibandronate 2.5 mg/day and placebo. These symptoms may indicate an acute phase reaction to bisphosphonate therapy, which occurs within 3 days of treatment and lasts 7 days or less; acute phase reactions were reported in 3-4% of daily oral users, 9% of monthly oral users, and 10% of quarterly parenteral users of ibandronate. In addition, insomnia was reported in 0.8-2.6% of patients taking ibandronate and depression in 1.3-2.2% during clinical trials.
Ocular adverse events may occur during ibandronate therapy. In clinical study, 1 case each of uveitis and scleritis were reported among 396 study patients who received oral monthly ibandronate; no other cases of ocular inflammation were reported in the 395 patients who received daily oral ibandronate in this study or in the cumulative 1605 patients who received oral daily ibandronate and 469 patients who received parenteral ibandronate in other pre-marketing study. Uveitis, nonspecific conjunctivitis, episcleritis, or scleritis have all been reported with pamidronate and these ocular reactions are expected to occur with other bisphosphonates as well. Nonspecific conjunctivitis seldom requires treatment and usually decreases in intensity during subsequent exposure to a bisphosphonate. However, no reported case of unilateral or bilateral scleritis resolved until the bisphosphonate was discontinued. More than one ocular side effect can occur at the same time; for instance, episcleritis may occur in conjunction with uveitis. In some instances, the drug may need to be discontinued in order for the ocular inflammation to resolve; for scleritis to resolve the bisphosphonate must be discontinued. Patients with visual impairment or ocular pain should be referred to an ophthalmologist.
Hypercholesterolemia has been reported in pre-marketing clinical study with ibandronate and was reported to occur in 4.8% of daily oral ibandronate- vs 4.2% placebo- treated patients and in 4.3% of daily oral- vs 1.5% quarterly parenteral- ibandronate treated patients. As expected with bisphosphonate treatment, a decrease in total alkaline phosphatase levels was seen in the active treatment groups as compared to placebo. There was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, hypocalcemia, or hypophosphatemia; however, patients receiving ibandronate in clinical practice have developed hypocalcemia. Hypercalciuria, hypocalcemia, hypomagnesemia, hypophosphatemia, elevated hepatic enzymes (indicating reversible hepatocellular injury), and thrombocytopenia have been reported in patients receiving bisphosphonate therapy.
Undefined tooth disorder has been reported in clinical study of oral ibandronate occurring at an incidence of 3.5% with daily ibandronate as compared to 2.3% with placebo. Osteonecrosis of the jaw has also been reported in patients receiving bisphosphonate therapy. Although the majority of patients affected receive either pamidronate or zoledronic acid for the management of metastatic cancer to the bone, there have been reports of osteonecrosis in patients receiving oral bisphosphonate therapy for the treatment of osteoporosis, including ibandronate. Most of the reported cases of osteonecrosis have appeared after dental tooth extraction; however, some cases have appeared spontaneously. It is not possible to determine if the reported events are related to bisphosphonates, concomitant drugs or other therapies (e.g., chemotherapy, radiotherapy, corticosteroid), a patient's underlying disease state, or other comorbid risk factors (e.g., anemia, infection, preexisting oral disease). The risk may increase with duration of exposure to the bisphosphonate. Typical signs and symptoms of osteonecrosis of the jaw include pain, swelling, infection, or poor healing of the gums, loosening of the teeth, numbness or a feeling of heaviness in the jaw, and drainage of exposed bone. If osteonecrosis of the jaw does develop during bisphosphonate therapy, it should be noted that dental surgery may exacerbate the condition. For patients requiring dental work, no data are available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. The treating physician and dentist should use their best clinical judgment to guide the management plan of each patient based on individual benefit and risk assessments. Based on a review of the available literature, treatments that have been used include local debridement, bone resection or other surgery, antimicrobials, antiseptic mouthwash, and hyperbaric oxygen. While a consensus on the best treatment strategies does not exist, the American Academy of Oral Medicine recommends prevention. Preventive measure include evaluation by a dentist prior to intravenous bisphosphonate initiation and within 3 months of oral bisphosphonate initiation, correction of dental complications prior to drug initiation, and continued regular follow-up with a dentist. For the treatment of osteonecrosis, recommendations include superficial debridement, bone resection when indicated, systemic antimicrobial for infections with culture-directed therapy or penicillin, amoxicillin, or clindamycin empirically, or use of chlorhexidine mouthwash 3-4 times daily. Discontinuation of the bisphosphonate once osteonecrosis occurs is controversial as the half-life of bisphosphonates within the bone is estimated to be years.
In October 2010, the FDA issued a safety communication warning of atypical bone fractures of the femur in patients receiving long-term bisphosphonate therapy for osteoporosis, including ibandronate. Definitive risk is not known, but most atypical fractures have been reported in patients taking long-term bisphosphonates. The FDA encourages patients to continue bisphosphonate therapy as directed, and encourages clinicians to periodically re-evaluate the need for continued therapy. If an atypical fracture occurs, discontinue the anti-resorptive agent. Advise patients to report new onset of groin or thigh pain, and evaluate the patient to rule out femoral fracture. Of note, this warning does not apply to those bisphosphonates used to treat Paget's disease or hypercalcemia of malignancy. Unlike most hip fractures, which usually occur at the femoral neck and/or in the intertrochanteric regions of the femur, these atypical femoral fractures occur in the subtrochanteric and/or proximal diaphyseal region of the femur; further, the atypical fractures are characterized as simple transverse or short oblique fractures within hypertrophied cortices, and are sustained with little to no trauma and without comminution. The estimated incidence of subtrochanteric fractures has increased since the introduction of bisphosphonates and yet constitutes less than 1% of all hip and femur fractures in the United States. Other co-morbid conditions associated with the development of atypical femoral fracture include: use of other anti-resorptive agents, glucocorticoid or proton pump inhibitor use, diabetes mellitus, rheumatoid arthritis, and vitamin D-deficiency. The manufacturer states that the optimal duration of treatment for osteoporosis is unknown and suggests that patients at low-risk for fracture be considered for drug discontinuation after 3-5 year of therapy. Continue to periodically re-evaluate for fracture risk after discontinuation of therapy.
Influenza-like symptoms have been associated with ibandronate and other bisphonates; these symptoms may indicate an acute phase reaction to bisphosphonate therapy, which occurs within 3 days of treatment and lasts 7 days or less. Acute phase reactions were reported in 3-4% of daily oral users, 9% of monthly oral users, and 10% of quarterly parenteral users of ibandronate. Other forms of infection have been noted during clinical study of ibandronate, though no drug-event causality has been determined. The following were reported in clinical study of daily oral ibandronate: unspecified infection (4.3% ibandronate vs. 3.4% placebo), pneumonia (5.9% vs. 4.3%). Cystitis was reported in 3.4% of daily oral ibandronate study patients and 1.9% of quarterly parenteral ibandronate patients and gastroenteritis in 3.4% and 1.5% of study patients respectively. In addition, bronchitis (6.8% with placebo, 2.8-10% with daily oral ibandronate, 2.5% with monthly oral ibandronate, 2.1% with quarterly parenteral ibandronate), influenza (not reported, 3.8-8% , 4%, 4.7%), urinary tract infection (4.2%, 1.8-5.5%, 2.3%, 2.6%), and upper respiratory tract infection (33.2%, 2-33.7%, 2%, 1.1%) have been reported in other trials.
Acute renal failure (unspecified) has been reported during post-marketing use of the intravenous ibandronate formulation. Prior to each injection, obtain serum creatinine. A renal function assessment is recommended after each injection for those patients with concomitant diseases or taking other potentially nephrotoxic drugs.
Oral and parenteral ibandronate use is contraindicated in any patient with a history of angioedema, serious rash, anaphylaxis or another severe hypersensitivity reaction to the drug or product excipients. Allergic reactions including anaphylactic reaction/shock with fatalities, angioedema, bronchospasm, asthma exacerbations, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous have been reported. If anaphylactic or another severe hypersensitivity/allergic reaction occurs, immediately discontinue ibandronate and initiate appropriate treatment. Ibandronate should be used cautiously in patients with known phosphonate hypersensitivity. Ibandronate injection therapy requires a specialized care setting. Proper medical support and monitoring measures should be readily available when the ibandronate injection is administered in case there is hypersensitivity or another severe reaction. Injectable ibandronate must be administered by the intravenous route only; avoid other injectable routes. If ibandronate undergoes intraarterial administration or paravenous administration, extravasation or tissue damage may occur.
A history of GI disease is an independent risk factor for the development of GI adverse reactions during oral bisphosphonate therapy. Oral ibandronate should be used with caution in patients with esophageal and GI disease, including dysphagia, esophagitis, gastritis, gastroesophageal reflux disease (GERD), hiatal hernia, duodenitis, ulcers, or GI perforation. Use of such formulations are contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as esophageal stricture or achalasia. Further, use of orally administered ibandronate is contraindicated in patients with an inability to stand or sit upright for at least 60 minutes after dose administration as the risk of esophagitis and esophageal ulceration/erosion appears to be greater in patients who lay down after taking this medicine. Prescribers and health care professionals should closely monitor patients for any signs or symptoms an esophageal reaction. Advise patients to discontinue ibandronate and seek medical attention if they develop dysphagia, odynophagia, or retrosternal pain. The risk of esophageal reactions increases in patients who do not follow the administration instructions. It is very important that patients understand and follow these instructions; direct observation may be required in those who cannot independently follow dosing instructions due to mental disability. In 2011, the FDA announced an ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of esophageal cancer. There have been conflicting findings from studies evaluating this risk. At the time of the announcement, FDA states that the benefits of oral bisphosphonate drugs in reducing the risk of serious fractures in people with osteoporosis continue to outweigh their potential risks.
Ibandronate is not recommended in patients with severe renal impairment as the drug will likely accumulate. No dosage adjustment is recommended by the manufacturer if creatinine clearance is > 30 ml/min (mild to moderate renal insufficiency). Until further evidence is available, ibandronate is not recommended for patients with creatinine clearance < 30 ml/min (renal failure). Specific precautions pertain to intravenous use. Treatment with other intravenous bisphosphonates (i.e., pamidronate and zoledronic acid) has been associated with renal toxicity manifested as deterioration in renal function (i.e., decreased creatinine clearance) and in rare cases, acute renal failure. The risk of serious renal toxicity with these bisphosphonates appears to be inversely related to the rate of drug administration. No cases of acute renal failure were observed during controlled clinical trials when parenteral ibandronate was administered as an IV bolus over 15-30 seconds; however, acute renal failure has been reported during post-marketing use. Patients who receive ibandronate injection should have a serum creatinine measured prior to each dose. Patients with concomitant diseases that have the potential for adverse effects on the kidney (i.e., pre-existing renal impairment, dehydration, multiple myeloma, advanced cancers, diabetes mellitus, and hypertension), or patients that are using other drugs with the potential for nephrotoxicity (i.e., NSAIDs, radiopaque contrast media, and aminoglycosides) should be assessed during treatment with ibandronate as clinically necessary. If deterioration in kidney function occurs, ibandronate should be withheld. About 50% of an IV dose is excreted in the urine. In humans, any ibandronate not deposited in bone is rapidly excreted.
Preexistent hypocalcemia is a contraindication and must be corrected before initiating ibandronate therapy. Similarly, vitamin D deficiency must be pretreated. Adequate intake of calcium and vitamin D are essential. This is most important for patients with Paget's disease who are to receive ibandronate. Ibandronate can decrease serum calcium and phosphate in these patients, who may have a higher rate of bone turnover.
Safety and efficacy of ibandronate have not been established in neonates, infants, children, or adolescents. Bisphosphonates have been used successfully in children for treatment of specific disease states (i.e., hypercalcemia of malignancy, idiopathic or glucocorticoid induced osteoporosis, osteogenesis imperfecta, Paget's disease). However, extreme caution must be used to ensure appropriate use in children; excessive doses of bisphosphonates may compromise skeletal quality during growth, despite concomitant increases in bone density. In a case report, inappropriate and excessive doses of pamidronate in a child resulted in osteopetrosis (abnormally dense and misshapen bone predisposed to fracture). It may be advisable to monitor biochemical markers of skeletal turnover when bisphosphonates are used in children to help assure clinicians that skeletal resorption is not excessively suppressed.
No overall differences in effectiveness or safety were observed between geriatric adults and younger adults during controlled clinical trials of oral and intravenous ibandronate, but greater sensitivity in some geriatric individuals cannot be ruled out. Geriatric adults may be at increased risk for the development of adverse GI reactions during ibandronate therapy. Increased age has been identified as an independent risk factor particularly for GI perforations, ulcers, or bleeding, but not necessarily esophageal events, with other bisphosphonates.
Ibandronate should be used cautiously in patients with a history of hypoparathyroidism, due to an increased risk of hypocalcemia.
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.
Osteonecrosis of the jaw has been reported in patients with cancer receiving treatment regimens which included bisphosphonates (most commonly pamidronate and zoledronic acid), but also occasionally in patients receiving chronic oral bisphosphonate therapy for osteoporosis, including ibandronate. The risk may increase with duration of exposure to the bisphosphonate. In patients with cancer receiving intravenous bisphosphonates, many patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures, such as tooth extraction, and many of these patients had signs of local infection including osteomyelitis; however, cases have appeared spontaneously. It would be prudent for all patients including those with concomitant risk factors (e.g. anemia, cancer, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, infection, poor oral hygiene) initiating bisphosphonate therapy to receive a dental examination with appropriate preventive dentistry and correction of dental complications prior to beginning treatment. Preventive measures such as these as well as continued regular follow-up with a dentist during bisphosphonate therapy are recommended by the American Academy of Oral Medicine as the best way to minimize the risk of osteonecrosis. Invasive dental procedures should be avoided, if possible, during treatment, but if they are necessary, should be performed by an experienced dentist with close patient follow-up. If osteonecrosis of the jaw does develop during bisphosphonate therapy, it should be noted that dental surgery may exacerbate the condition. For patients requiring dental work, no data are available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. In addition, discontinuing the bisphosphonate once osteonecrosis develops is controversial as the estimated half-life of bisphosphonates in the bone is years.
Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with ibandronate regarding this laboratory test interference have not been performed.
Recommendations for calcium and vitamin D intake:
-To promote general bone health, guidelines for the prevention and treatment of osteoporosis recommend a target daily intake of 1,200 mg of elemental calcium for females older than 50 years and males older than 70 years. Target daily elemental calcium intake for males 70 years or younger is 1,000 mg. Daily vitamin D intake of 20 to 25 mcg (800 to 1,000 international units) is recommended for patients 50 years of age and older.
For the treatment of osteoporosis:
-once monthly oral regimen for postmenopausal osteoporosis:
Oral dosage:
Adult postmenopausal females: 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. 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.
-once every 3 months injectable regimen for postmenopausal osteoporosis:
Intravenous dosage:
Adult postmenopausal females : 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.
-for corticosteroid-induced osteoporosis* in men and women:
Oral dosage:
Adults: 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.
Intravenous dosage:
Adults: 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.
For osteoporosis prophylaxis:
-once monthly oral regimen for prevention of postmenopausal osteoporosis:
Oral dosage:
Adult postmenopausal females: 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.
-once monthly oral regimen for corticosteroid-induced osteoporosis prophylaxis* in men and women:
Oral dosage:
Adults: 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.
For the treatment of Paget's disease*:
Intravenous dosage:
Adults: 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.
For the treatment of hypercalcemia* of malignancy:
Intravenous dosage:
Adults: 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.
For the prevention of adverse skeletal events due to bone metastases* in selected cancer patients (e.g., breast cancer):
Oral dosage:
Adults: 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.
Intravenous dosage:
Adults: 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.
Therapeutic Drug Monitoring:
In patients receiving prevention or treatment of osteoporosis, evidence suggests that bone mineral density (BMD) monitoring during the period of active treatment (3 to 5 years) is not needed for most patients. However, reassess fracture risk periodically to help determine the need for continued treatment. The FRAX calculator or Fracture Risk Assessment Tool, developed by World Health Organization, is available for download or online calculation via the World Wide Web.
Maximum Dosage Limits:
-Adults
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.
-Geriatric
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.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment required.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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, 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.
Acetaminophen; Ibuprofen: (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.
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.
Amlodipine; Celecoxib: (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.
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; 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.
Bupivacaine; Meloxicam: (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.
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.
Celecoxib: (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.
Celecoxib; Tramadol: (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.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (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.
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.
Diclofenac: (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.
Diclofenac; Misoprostol: (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.
Diflunisal: (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.
Diphenhydramine; Ibuprofen: (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.
Diphenhydramine; Naproxen: (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.
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.
Ethiodized Oil: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Etodolac: (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.
Fenoprofen: (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.
Ferric Maltol: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
Flurbiprofen: (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.
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.
Hydrocodone; Ibuprofen: (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.
Ibuprofen: (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.
Ibuprofen; Famotidine: (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.
Ibuprofen; Oxycodone: (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.
Ibuprofen; Pseudoephedrine: (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.
Indomethacin: (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.
Iodixanol: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Iohexol: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Iomeprol: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Iopamidol: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Iopromide: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Ioversol: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Iron Salts: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
Iron Salts: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
Iron: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
Isosulfan Blue: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
Ketoprofen: (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.
Ketorolac: (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.
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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
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.
Meclofenamate Sodium: (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.
Mefenamic Acid: (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.
Meloxicam: (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.
Nabumetone: (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.
Naproxen: (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.
Naproxen; Esomeprazole: (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.
Naproxen; Pseudoephedrine: (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.
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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
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.
Oxaprozin: (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.
Paromomycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
Piroxicam: (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.
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 Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
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.
Sulindac: (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.
Sumatriptan; Naproxen: (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.
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.
Tolmetin: (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.
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.
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
-Route-Specific Pharmacokinetics
Oral Route
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.
-Special Populations
Renal Impairment
Reduced renal function may result in reduced clearance of ibandronate; following 0.5 mg of intravenous ibandronate, patients with CrCl of 40-70 mL/min had a 55% higher exposure to ibandronate compared to patients with CrCl > 90 mL/min. Similarly, patients with CrCl < 30 mL/min had more than a 2-fold increase in exposure compared to healthy subjects. Ibandronate is dialyzable. A 1-mg dose of intravenous ibandronate was efficiently removed by hemodialysis in 12 end stage renal disease (ESRD) patients on chronic hemodialysis. The concentration of ibandronate was reduced by 47% with every passage through the dialyzer and approximately 36% of the total amount of ibandronate was removed by the first dialysis treatment.