Ibandronate Drug Information
Generic name: IBANDRONATE SODIUM
Uses of Ibandronate
Treatment and Prevention of Postmenopausal Osteoporosis Ibandronate sodium tablets are indicated for
the treatment and prevention of osteoporosis in postmenopausal women. Ibandronate sodium increases bone mineral density (BMD) and reduces the incidence of vertebral fractures.
Important Limitations of Use Theoptimalduration of use has not been determined.
The safety and effectiveness of ibandronate sodium tablets for the treatment of osteoporosis are based on clinical data of three years duration. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use.
Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.
Dosage & Administration of Ibandronate
Dosage Information
The dose of ibandronate sodium tablet is one 150 mg tablet taken once monthly on the same date each month.
Important
Administration Instructions Instruct Patients to do the following: Take ibandronate sodium tablets at least 60 minutes before the first food or drink (other than water) of the day or before taking any oral medication or supplementation, including calcium, antacids, or vitamins to maximize absorption and clinical benefit, (see DRUG INTERACTIONS ). Avoid the use of water with supplements including mineral water because they may have a higher concentration of calcium. Swallow ibandronate sodium tablets whole with a full glass of plain water (6 to 8 oz) while standing or sitting in an upright position to reduce the potential for esophageal irritation. Avoid lying down for 60 minutes after taking ibandronate sodium tablets (see WARNINGS AND PRECAUTIONS ). Do not chew or suck the tablet because of a potential for oropharyngeal ulceration.
Do not eat, drink anything except plain water, or take other medications for at least 60 minutes after taking ibandronate sodium tablets.
Recommendations for Calcium and Vitamin D Supplementation Instruct patients to take supplemental
calcium and vitamin D if their dietary intake is inadequate. Avoid the use of calcium supplements within 60 minutes of ibandronate sodium administration because co-administration of ibandronate sodium tablets and calcium may interfere with the absorption of ibandronate sodium (see DRUG INTERACTIONS ).
Administration Instructions for Missed Once-Monthly Doses
If the once-monthly dose is missed, instruct patients to do the following: If the next scheduled ibandronate sodium tablet day is more than 7 days away, take one ibandronate sodium 150 mg tablet in the morning following the date that it is remembered. If the next scheduled ibandronate sodium tablets day is only 1 to 7 days away, wait until the subsequent month’s scheduled ibandronate sodium tablet day to take their tablet. For subsequent monthly doses for both of the above scenarios, instruct patients to return to their original schedule by taking one ibandronate sodium 150 mg tablet every month on their previous chosen day.
Side Effects of Ibandronate
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Treatment and Prevention of Postmenopausal Osteoporosis Daily Dosing The safety of ibandronate sodium tablets 2.5 mg once daily in the treatment and prevention of postmenopausal osteoporosis was assessed in 3577 patients aged 41 – 82 years. The duration of the trials was 2 to 3 years, with 1134 patients exposed to placebo and 1140 exposed to ibandronate sodium tablets 2.5 mg.
Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H2 antagonists were included in these clinical trials. All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily. The incidence of all-cause mortality was 1% in the placebo group and 1.2% in the ibandronate sodium tablets 2.5 mg daily group.
The incidence of serious adverse reactions was 20% in the placebo group and 23% in the ibandronate sodium tablets 2.5 mg daily group. The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the ibandronate sodium tablets 2.5 mg daily group and the placebo group. Table 1 lists adverse reactions from the treatment and prevention studies reported in greater than or equal to 2% of patients and more frequently in patients treated daily with ibandronate sodium tablets than patients treated with placebo.
Table 1 Adverse Reactions Occurring at an Incidence Greater Than or Equal to 2% and in More Patients Treated with Ibandronate Sodium Tablets Than in Patients Treated with Placebo Daily in the Osteoporosis Treatment and Prevention Studies Body System Placebo % (n=1134) Ibandronate Sodium Tablets 2.5 mg % (n=1140) Body as a Whole Back Pain 12 14 Pain in Extremity 6 8 Asthenia 2 4 Allergic Reaction 2 3 Digestive System Dyspepsia 10 12 Diarrhea 5 7 Tooth Disorder 2 4 Vomiting 2 3 Gastritis 2 2 Musculoskeletal System Myalgia 5 6 Joint Disorder 3 4 Arthritis 3 3 Nervous System Headache 6 7 Dizziness 3 4 Vertigo 3 3 Respiratory System Upper Respiratory Infection 33 34 Bronchitis 7 10 Pneumonia 4 6 Pharyngitis 2 3 Urogenital System Urinary Tract Infection 4 6 Gastrointestinal Adverse Reactions The incidence of selected gastrointestinal adverse reactions in the placebo and ibandronate sodium tablets 2.5 mg daily groups were: dyspepsia (10% vs. 12%), diarrhea (5% vs. 7%), and abdominal pain (5% vs. 6%). Musculoskeletal Adverse Reactions The incidence of selected musculoskeletal adverse reactions in the placebo and ibandronate sodium tablets 2.5 mg daily groups were: back pain (12% vs. 14%), arthralgia (14% vs. 14%) and myalgia (5% vs. 6%). Ocular Adverse Events Reports in the medical literature indicate that bisphosphonates may be associated with ocular inflammation such as iritis and scleritis. In some cases, these events did not resolve until the bisphosphonate was discontinued. There were no reports of ocular inflammation in studies with ibandronate sodium tablets 2.5 mg daily.
Monthly Dosing The safety of ibandronate sodium tablets 150 mg once monthly in the treatment of postmenopausal osteoporosis was assessed in a two year trial which enrolled 1583 patients aged 54 to 81 years, with 395 patients exposed to ibandronate sodium tablets 2.5 mg daily and 396 exposed to ibandronate sodium tablets 150 mg monthly. Patients with active or significant pre-existing gastrointestinal disease were excluded from this trial. Patients with dyspepsia or concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H2 antagonists were included in this study.
All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily. After one year, the incidence of all-cause mortality was 0.3% in both the ibandronate sodium tablets 2.5 mg daily group and the ibandronate sodium tablets 150 mg monthly group. The incidence of serious adverse events was 5% in the ibandronate sodium tablets 2.5 mg daily group and 7% in the ibandronate sodium tablets 150 mg monthly group.
The percentage of patients who withdrew from treatment due to adverse events was 9% in the ibandronate sodium tablets 2.5 mg daily group and 8% in the ibandronate sodium tablets 150 mg monthly group. Table 2 lists the adverse events reported in greater than or equal to 2% of patients. Table 2 Adverse Events with an Incidence of at Least 2% in Patients Treated with Ibandronate Sodium Tablets 2.5 mg Daily or 150 mg Once-Monthly for Treatment of Postmenopausal Osteoporosis Body System/Adverse Event Ibandronate sodium tablets 2.5 mg Daily % (n=395) Ibandronate sodium tablets 150 mg Monthly % (n=396) Vascular Disorders Hypertension 7.3
Gastrointestinal Disorders Dyspepsia 7.1 5.6 Nausea 4.8 5.1 Diarrhea 4.1 5.1 Constipation
2.5
Nasopharyngitis 4.3 3.5 Bronchitis 3.5 2.5 Urinary Tract Infection 1.8 2.3 Upper
Respiratory Tract Infection 2.0
Nervous System Disorders Headache 4.1 3.3 Dizziness 1.0 2.3 General Disorders and
Administration Site Conditions Influenza-like Illness b 0.8
Skin and Subcutaneous Tissue Disorders Rash c 1.3 2.3 Psychiatric Disorders Insomnia
0.8 2.0 a Combination of abdominal pain and abdominal pain upper b Combination of influenza-like illness and acute phase reaction c Combination of rash pruritic, rash macular, rash papular, rash generalized, rash erythematous, dermatitis, dermatitis allergic, dermatitis medicamentosa, erythema and exanthema Gastrointestinal Adverse Events The incidence of adverse events in the ibandronate sodium tablets 2.5 mg daily and ibandronate sodium tablets 150 mg monthly groups were: dyspepsia (7% vs. 6%), diarrhea (4% vs. 5%), and abdominal pain (5% vs. 8%). Musculoskeletal Adverse Events The incidence of adverse events in the ibandronate sodium tablets 2.5 mg daily and ibandronate sodium tablets 150 mg monthly groups were: back pain (4% vs. 5%), arthralgia (4% vs. 6%) and myalgia (1% vs. 2%). Acute Phase Reactions Symptoms consistent with acute phase reactions have been reported with bisphosphonate use. Over the two years of the study, the overall incidence of acute phase reaction symptoms was 3% in the ibandronate sodium tablets 2.5 mg daily group and 9% in the ibandronate sodium tablets 150 mg monthly group. These incidence rates are based on the reporting of any of 33 acute-phase reaction like symptoms within 3 days of the monthly dosing and lasting 7 days or less.
Influenza like illness was reported in no patients in the ibandronate sodium tablets 2.5 mg daily group and 2% in the ibandronate sodium tablets 150 mg monthly group. Ocular Adverse Events Two patients who received ibandronate sodium tablets 150 mg once-monthly experienced ocular inflammation, one was a case of uveitis and the other scleritis. One hundred sixty postmenopausal women without osteoporosis participated in a 1-year, double-blind, placebo-controlled study of ibandronate sodium tablets 150 mg once-monthly for prevention of bone loss.
Seventy-seven subjects received ibandronate sodium tablets and 83 subjects received placebo. The overall pattern of adverse events was similar to that previously observed.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of ibandronate sodium tablets or bisphosphonate products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity Allergic reactions including anaphylactic reaction/shock with fatalities, angioedema, bronchospasm, asthma exacerbations, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous have been reported (see CONTRAINDICATIONS ). Hypocalcemia Hypocalcemia has been reported in patients treated with ibandronate sodium tablets (see WARNINGS AND PRECAUTIONS ). Musculoskeletal Bone, joint, or muscle pain, described as severe or incapacitating, has been reported rarely (see WARNINGS AND PRECAUTIONS ) ; low-energy femoral shaft and subtrochanteric fractures, and atypical fractures of other bones . Jaw Osteonecrosis Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal, have been reported in patients treated with ibandronate sodium tablets (see WARNINGS AND PRECAUTIONS ).
Warnings & Cautions for Ibandronate
Upper Gastrointestinal Adverse Reactions Ibandronate sodium tablets, like other bisphosphonates administered orally
may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when ibandronate sodium tablets are given to patients with active upper gastrointestinal problems (such as known Barrett's esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. In some cases, these have been severe and required hospitalization.
Physicians should therefore be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue ibandronate sodium tablets and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. The risk of severe esophageal adverse experiences appears to be greater in patients who lie down after taking oral bisphosphonates and/or who fail to swallow it with the recommended full glass (6 to 8 oz) of water, and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Therefore, it is very important that the full dosing instructions are provided to, and understood by, the patient (see Dosage and Administration ). In patients who cannot comply with dosing instructions due to mental disability, therapy with ibandronate sodium tablets should be used under appropriate supervision.
There have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications, although no increased risk was observed in controlled clinical trials.
Hypocalcemia and Mineral Metabolism Hypocalcemia has been reported in patients taking ibandronate
sodium tablets. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting ibandronate sodium tablets therapy. Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate (see Dosage and Administration ).
Musculoskeletal Pain Severe and occasionally incapacitating bone, joint, and/or muscle pain has
been reported in patients taking ibandronate sodium tablets and other bisphosphonates (see Adverse Reactions ). The time to onset of symptoms varied from one day to several months after starting the drug. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.
Consider discontinuing use if severe symptoms develop.
Jaw Osteonecrosis Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is
generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates, including ibandronate sodium. Known risk factors for osteonecrosis of the jaw include invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders (e.g., periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures). The risk of ONJ may increase with duration of exposure to bisphosphonates. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk for ONJ. Clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on individual benefit/risk assessment.
Patients who develop osteonecrosis of the jaw while on bisphosphonate therapy should receive care by an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment.
Atypical Fractures Including Femoral Fractures Atypical, low-energy, or low-trauma fractures of the
femoral shaft have been reported during treatment with bisphosphonates including ibandronate in patients with osteoporosis. Atypical femur and other fractures most commonly occur with minimal or no trauma to the affected area. These fractures occurred anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are traverse or short oblique in orientation without evidence of comminution.
Atypical fractures of other bones have also been reported. They may be bilateral. These fractures can also occur in osteoporotic patients who have not been treated with bisphosphonates.
Concomitant treatment with glucocorticoids may also induce these fractures. Prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs was reported by patients. Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture.
Bony pain in other locations should also be considered for evaluation of atypical fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Risk/benefit of continuing bisphosphonate therapy should be re-evaluated in these patients and interruption of bisphosphonate therapy should be considered.
Severe Renal Impairment Ibandronate sodium tablets are not recommended for use in
patients with severe renal impairment (creatinine clearance of less than 30 mL/min).
Drug Interactions with Ibandronate
Calcium Supplements/Antacids Products containing calcium and other multivalent cations (such as aluminum
magnesium, iron) are likely to interfere with absorption of ibandronate sodium tablets. Therefore, instruct patients to take ibandronate sodium tablets at least 60 minutes before any oral medications, including medications containing multivalent cations (such as antacids, supplements or vitamins). Also, patients should wait at least 60 minutes after dosing before taking any other oral medications ( see DOSAGE AND ADMINISTRATION ).
Aspirin/Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Because aspirin, NSAIDs, and bisphosphonates are all associated with gastrointestinal irritation, caution should be exercised in the concomitant use of aspirin or NSAIDs with ibandronate sodium tablets.
H2 Blockers
In healthy volunteers, co-administration with ranitidine resulted in a 20% increased bioavailability of ibandronate, which was not considered to be clinically relevant (see CLINICAL PHARMACOLOGY ).
Drug/Laboratory Test Interactions Bisphosphonates are known to interfere with the use of
bone-imaging agents. Specific studies with ibandronate have not been performed.
Pregnancy Safety for Ibandronate
Pregnancy Risk Summary Ibandronate sodium tablets is not indicated for use in women of reproductive potential. There are no data with ibandronate sodium use in pregnant women to inform any drug-associated risks. In reproductive toxicity studies in the rat, ibandronate sodium caused post-implantation loss and obstruction of labor with maternal and fetal periparturient mortality at greater than or equal to 3 times human exposure at the recommended 2.5 mg daily oral dose, or at greater than or equal to 1 times human exposure at the recommended 150 mg once-monthly oral dose.
In pregnant rats, kidney developmental toxicity occurred in offspring at greater than or equal to 30 times the daily 2.5 mg human dose or at greater than or equal to 9 times the once-monthly 150 mg human dose. In rat reproductive studies, impaired pup neuromuscular development was observed at 45 times the daily 2.5 mg dose and 13 times the once-monthly 150 mg dose. In reproductive studies in the rabbit, ibandronate sodium caused maternal mortality at greater than or equal to 8 times the daily 2.5 mg dose and greater than or equal to 4 times the once-monthly 150 mg dose ( see Data ). Data Animal Data In female rats given ibandronate at oral doses greater than or equal to 3 times human exposure at the recommended daily oral dose of 2.5 mg or greater than or equal to 1 times human exposure at the recommended once-monthly oral dose of 150 mg beginning 14 days before mating and continuing through lactation, maternal deaths were observed at the time of delivery in all dose groups.
Perinatal pup loss in dams given doses producing 45 times human exposure at the recommended daily dose and 13 times human exposure at the recommended once-monthly dose was likely related to maternal dystocia. Calcium supplementation did not completely prevent dystocia and periparturient mortality in any of the treated groups at greater than or equal to 16 times the recommended daily dose and greater than or equal to 4.6 times the recommended once-monthly dose. A low incidence of postimplantation loss was observed in rats treated from 14 days before mating throughout lactation or during gestation, only at doses causing maternal dystocia and periparturient mortality.
In pregnant rats dosed orally from gestation day 17 through lactation day 21 (following closure of the hard palate through weaning), maternal toxicity, including dystocia and mortality, fetal perinatal and postnatal mortality, were observed at doses equivalent to human exposure at the recommended daily dose and greater than or equal to 4 times the recommended once-monthly dose. Periparturient mortality has also been observed with other bisphosphonates and appears to be a class effect related to inhibition of skeletal calcium mobilization resulting in hypocalcemia and dystocia. Exposure of pregnant rats during the period of organogenesis resulted in an increased fetal incidence of RPU (renal pelvis ureter) syndrome at oral doses producing 30 times human exposure at the recommended daily oral dose of 2.5 mg and greater than or equal to 9 times human exposure at the recommended once-monthly oral dose of 150 mg.
Impaired pup neuromuscular development (cliff avoidance test) was observed at 45 times human exposure at the daily dose and 13 times the once-monthly dose. In pregnant rabbits treated orally with ibandronate during gestation at doses greater than or equal to 8 times the recommended human daily oral dose of 2.5 mg and greater than or equal to 4 times the recommended human once-monthly oral dose of 150 mg, dose-related maternal mortality was observed in all treatment groups. The deaths occurred prior to parturition and were associated with lung edema and hemorrhage.
No significant fetal anomalies were observed. Exposure multiples for the rat studies were calculated for the recommended daily oral dose of 2.5 mg or once-monthly dose of 150 mg based on area under the curve (AUC) comparison. Exposure multiples for the rabbit study were calculated for the recommended human daily oral dose of 2.5 mg or once-monthly dose of 150 mg based on dose/body surface area comparison.
Doses used in pregnant animals were 1, 4, 5, 6, 16, 10, 20, 30, 60 or 100 mg/kg/day in rats, and 1, 4 or 20 mg/kg/day in rabbits.
Pediatric Use of Ibandronate
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for Ibandronate
Ibandronate sodium tablets are contraindicated in patients with the following conditions: Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia (see Warnings and Precautions ) Inability to stand or sit upright for at least 60 minutes ( see Dosage and Administration , and Warnings and Precautions ) Hypocalcemia ( see Warnings and Precautions ) Known hypersensitivity to ibandronate sodium tablets or to any of its excipients. Cases of anaphylaxis have been reported ( see Adverse Reactions ). Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia Inability to stand or sit upright for at least 60 minutes Hypocalcemia Hypersensitivity to ibandronate sodium tablets
Overdosage Information for Ibandronate
No specific information is available on the treatment of overdosage of ibandronate sodium tablets. However, based on knowledge of this class of compounds, oral overdosage may result in hypocalcemia, hypophosphatemia, and upper gastrointestinal adverse events, such as upset stomach, dyspepsia, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronate sodium tablets.
Due to the risk of esophageal irritation, vomiting should not be induced, and the patient should remain fully upright. Dialysis would not be beneficial.
Clinical Studies of Ibandronate
Treatment of Postmenopausal Osteoporosis Daily Dosing
The effectiveness and safety of ibandronate sodium tablets were demonstrated in a randomized, double-blind, placebo-controlled, multinational study (Treatment Study) of 2946 women aged 55 to 80 years, who were on average 21 years postmenopause, who had lumbar spine BMD 2 to 5 SD below the premenopausal mean (T-score) in at least one vertebra, and who had 1 to 4 prevalent vertebral fractures. Ibandronate sodium tablets were evaluated at oral doses of 2.5 mg daily and 20 mg intermittently. The main outcome measure was the occurrence of new radiographically diagnosed vertebral fractures after 3 years of treatment.
The diagnosis of an incident vertebral fracture was based on both qualitative diagnosis by the radiologist and quantitative morphometric criterion. The morphometric criterion required the dual occurrence of 2 events: a relative height ratio or relative height reduction in a vertebral body of at least 20%, together with at least a 4 mm absolute decrease in height. All women received 400 international units vitamin D and 500 mg calcium supplementation per day.
Effect on Fracture Incidence Ibandronate sodium tablets 2.5 mg daily significantly reduced the incidence of new vertebral (primary efficacy measure) and of new and worsening vertebral fractures. Over the course of the 3-year study, the risk for vertebral fracture was 9.6% in the placebo-treated women and 4.7% in the women treated with ibandronate sodium tablets 2.5 mg (p<0.001) (see Table 3). Table 3 Effect of Ibandronate Sodium Tablets on the Incidence of Vertebral Fracture in the 3-Year Osteoporosis Treatment Study* Proportion of Patients with Fracture (%) Placebo n=975 Ibandronate sodium tablets 2.5 mg Daily n=977 Absolute Risk Reduction (%) 95% CI Relative Risk Reduction (%) 95% CI New Vertebral Fracture 9.6 4.7 4.9 52** 0-3 Year New and Worsening Vertebral Fracture 10.4 5.1 5.3 52 0-3 Year Clinical (Symptomatic) Vertebral Fracture 5.3 2.8 2.5 49 0-3 Year * The endpoint value is the value at the study's last time point, 3 years, for all patients who had a fracture identified at that time; otherwise, the last postbaseline value prior to the study's last time point is used. ** p=0.0003 vs. placebo Ibandronate sodium tablets 2.5 mg daily did not reduce the incidence of nonvertebral fractures (secondary efficacy measure). There was a similar number of nonvertebral osteoporotic fractures at 3 years reported in women treated with ibandronate sodium tablets 2.5 mg daily and placebo. The two treatment groups were also similar with regard to the number of fractures reported at the individual nonvertebral sites: pelvis, femur, wrist, forearm, rib, and hip.
Bone Mineral Density (BMD) Ibandronate sodium tablets significantly increased BMD at the lumbar spine and hip relative to treatment with placebo. In the 3-year osteoporosis treatment study, ibandronate sodium tablets 2.5 mg daily produced increases in lumbar spine BMD that were progressive over 3 years of treatment and were statistically significant relative to placebo at 6 months and at all later time points. Lumbar spine BMD increased by 6.4% after 3 years of treatment with 2.5 mg daily ibandronate sodium tablets compared with 1.4% in the placebo group.
Table 4 displays the significant increases in BMD seen at the lumbar spine, total hip, femoral neck, and trochanter compared to placebo. Table 4 Mean Percent Change in BMD from Baseline to Endpoint in Patients Treated Daily with Ibandronate Sodium Tablets 2.5 mg or Placebo in the 3-Year Osteoporosis Treatment Study The endpoint value is the value at the study's last time point, 3 years, for all patients who had BMD measured at that time; otherwise, the last postbaseline value prior to the study's last time point is used. Placebo Ibandronate sodium tablets 2.5 mg Daily Lumbar Spine 1.4 (n=693) 6.4 (n=712) Total Hip -0.7 (n=638) 3.1 (n=654) Femoral Neck -0.7 (n=683) 2.6 (n=699) Trochanter 0.2 (n=683) 5.3 (n=699) Bone Histology The effects of ibandronate sodium tablets 2.5 mg daily on bone histology were evaluated in iliac crest biopsies from 16 women after 22 months of treatment and 20 women after 34 months of treatment.
The histological analysis of bone biopsies showed bone of normal quality and no indication of osteomalacia or a mineralization defect. Once-Monthly Dosing The effectiveness and safety of ibandronate sodium tablets once-monthly were demonstrated in a randomized, double-blind, multinational, noninferiority trial in 1602 women aged 54 to 81 years, who were on average 18 years postmenopause, and had L2 to L4 lumbar spine BMD T-score below -
SD at baseline.
The main outcome measure was the comparison of the percentage change from baseline in lumbar spine BMD after 1 year of treatment with once-monthly ibandronate (100 mg, 150 mg) to daily ibandronate (2.5 mg). All patients received 400 international units vitamin D and 500 mg calcium supplementation per day. Ibandronate sodium tablets 150 mg once-monthly (n=327) was shown to be noninferior to ibandronate sodium tablets 2.5 mg daily (n=318) in lumbar spine BMD in a 1-year, double-blind, multicenter study of women with postmenopausal osteoporosis. In the primary efficacy analysis (per-protocol population), the mean increases from baseline in lumbar spine BMD at 1 year were 3.86% (95% CI: 3.40%, 4.32%) in the 2.5 mg daily group and 4.85% (95% CI: 4.41%, 5.29%) in the 150 mg once-monthly group; the mean difference between 2.5 mg daily and 150 mg once-monthly was 0.99% (95% CI: 0.38%, 1.60%), which was statistically significant (p=0.002). The results of the intent-to-treat analysis were consistent with the primary efficacy analysis.
The 150 mg once-monthly group also had consistently higher BMD increases at the other skeletal sites compared to the 2.5 mg daily group.
Prevention of Postmenopausal Osteoporosis Daily Dosing
The safety and effectiveness of ibandronate sodium tablets 2.5 mg daily for the prevention of postmenopausal osteoporosis were demonstrated in a randomized, double-blind, placebo-controlled 2-year study (Prevention Study) of 653 postmenopausal women without osteoporosis at baseline. Women were aged 41 to 82 years, were on average 8.5 years postmenopause, and had lumbar spine BMD T-scores greater than -2.5. Women were stratified according to time since menopause (1 to 3 years, greater than 3 years) and baseline lumbar spine BMD (T-score: greater than -1, -1 to -2.5). The study compared daily ibandronate sodium tablets at three dose levels (0.5 mg, 1.0 mg, 2.5 mg) with placebo. All women received 500 mg of supplemental calcium per day.
The primary efficacy measure was the change in BMD of lumbar spine after 2 years of treatment. Ibandronate sodium tablets 2.5 mg daily resulted in a mean increase in lumbar spine BMD of 3.1% compared with placebo following 2 years of treatment. Increases in BMD were seen at 6 months and at all later time points.
Irrespective of the time since menopause or the degree of pre-existing bone loss, treatment with ibandronate sodium tablets resulted in a higher BMD response at the lumbar spine compared with placebo across all four baseline strata. Compared with placebo, treatment with ibandronate sodium tablets 2.5 mg daily increased BMD of the total hip by 1.8%, the femoral neck by 2.0%, and the trochanter by 2.1%. Once-Monthly Dosing The safety and effectiveness of ibandronate sodium tablets 150 mg once-monthly for the prevention of postmenopausal osteoporosis were demonstrated in a randomized, double-blind, placebo-controlled 1-year study (Monthly Prevention Study) of 160 postmenopausal women with low bone mass at baseline (T-score of -1 to -2.5). Women, aged 46 to 60 years, were on average 5.4 years postmenopause. All women received 400 international units of vitamin D and 500 mg calcium supplementation daily.
The primary efficacy measure was the relative change in BMD at the lumbar spine after 1 year of treatment. Ibandronate sodium tablets 150 mg once-monthly resulted in a mean increase in lumbar spine BMD of 4.12% (95% confidence interval 2.96 to 5.28) compared with placebo following 1 year of treatment (p<0.0001), based on a 3.73% and -0.39% mean change in BMD from baseline in the 150 mg once-monthly ibandronate sodium tablets and placebo treatment groups, respectively. BMD at other skeletal sites was also increased relative to baseline values.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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