|
|
| (15 intermediate revisions by one other user not shown) |
| Line 1: |
Line 1: |
| {{DrugProjectFormSinglePage
| | #REDIRECT [[Ibandronate]] |
| |authorTag={{DB}}
| |
| |genericName=Ibandronate sodium
| |
| |aOrAn=a
| |
| |drugClass=bone density conservation agent
| |
| |indicationType=treatment
| |
| |indication=osteoporosis
| |
| |adverseReactions=hypertension,abdominal pain, diarrhea, indigestion, nausea,
| |
| back ache, pain in limb, headache, bronchitis, upper respiratory infection
| |
| |blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b>
| |
| |blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
| |
| |fdaLIADAdult=====Treatment and Prevention of Postmenopausal Osteoporosis====
| |
| | |
| *BONIVA is indicated for the treatment and prevention of osteoporosis in postmenopausal women. BONIVA increases bone mineral density (BMD) and reduces the incidence of vertebral fractures.
| |
| | |
| '''Important Limitations of Use'''
| |
| | |
| *The optimal duration of use has not been determined. The safety and effectiveness of BONIVA 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.
| |
| *Dosing information:
| |
| :* The dose of BONIVA is one 150 mg tablet taken once monthly on the same date each month.
| |
| |offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ibandronic acid in adult patients.
| |
| |offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ibandronic acid in adult patients.
| |
| |offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ibandronic acid in pediatric patients.
| |
| |offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ibandronic acid in pediatric patients.
| |
| |contraindications=BONIVA is contraindicated in patients with the following conditions:
| |
| | |
| *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.
| |
| *Known hypersensitivity to BONIVA or to any of its excipients. Cases of anaphylaxis have been reported.
| |
| |warnings='''Upper Gastrointestinal Adverse Reactions'''
| |
| | |
| *BONIVA, 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 BONIVA is 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 BONIVA 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 (6-8 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 [2.2]). In patients who cannot comply with dosing instructions due to mental disability, therapy with BONIVA 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 BONIVA. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting BONIVA therapy. Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate.
| |
| | |
| '''Musculoskeletal Pain'''
| |
| | |
| *Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking BONIVA and other bisphosphonates. 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 BONIVA. 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), 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 Subtrochanteric and Diaphyseal Femoral Fractures'''
| |
| | |
| *Atypical, low-energy, or low-trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates.
| |
| | |
| *Atypical femur fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g., prednisone) at the time of fracture.
| |
| | |
| *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. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment, on an individual basis.
| |
| | |
| '''Severe Renal Impairment'''
| |
| | |
| *BONIVA is not recommended for use in patients with severe renal impairment (creatinine clearance of less than 30 mL/min).
| |
| |clinicalTrials=*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 BONIVA 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 BONIVA 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 BONIVA 2.5 mg daily group. The incidence of serious adverse reactions was 20% in the placebo group and 23% in the BONIVA 2.5 mg daily group. The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the BONIVA 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 BONIVA than patients treated with placebo.
| |
| | |
| [[File:Boniva table 1.png|600px|thumbnail|left]] | |
| {{clear}}
| |
| | |
| '''Gastrointestinal Adverse Reactions'''
| |
| | |
| *The incidence of selected gastrointestinal adverse reactions in the placebo and BONIVA 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 BONIVA 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 BONIVA 2.5 mg daily.
| |
| | |
| '''Monthly Dosing'''
| |
| | |
| *The safety of BONIVA 150 mg once monthly in the treatment of postmenopausal osteoporosis was assessed in a two year trial which enrolled 1583 patients aged 54 – 81 years, with 395 patients exposed to BONIVA 2.5 mg daily and 396 exposed to BONIVA 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 BONIVA 2.5 mg daily group and the BONIVA 150 mg monthly group. The incidence of serious adverse events was 5% in the BONIVA 2.5 mg daily group and 7% in the BONIVA 150 mg monthly group. The percentage of patients who withdrew from treatment due to adverse events was 9% in the BONIVA 2.5 mg daily group and 8% in the BONIVA 150 mg monthly group. Table 2 lists the adverse events reported in greater than or equal to 2% of patients.
| |
| | |
| [[File:Boniva table 2.png|600px|thumbnail|left]]
| |
| {{clear}}
| |
| | |
| '''Gastrointestinal Adverse Events'''
| |
| | |
| *The incidence of adverse events in the BONIVA 2.5 mg daily and BONIVA 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 BONIVA 2.5 mg daily and BONIVA 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 BONIVA 2.5 mg daily group and 9% in the BONIVA 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 BONIVA 2.5 mg daily group and 2% in the BONIVA 150 mg monthly group.
| |
| | |
| '''Ocular Adverse Events'''
| |
| | |
| *Two patients who received BONIVA 150 mg once-monthly experienced ocular inflammation, one was a case of uveitis and the other scleritis.
| |
| | |
| *One hundred sixty (160) postmenopausal women without osteoporosis participated in a 1-year, double-blind, placebo-controlled study of BONIVA 150 mg once-monthly for prevention of bone loss. Seventy-seven subjects received BONIVA and 83 subjects received placebo. The overall pattern of adverse events was similar to that previously observed.
| |
| |postmarketing=*The following adverse reactions have been identified during postapproval use of BONIVA. 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; in some cases fatal, angioedema, bronchospasm, asthma exacerbations, and rash have been reported.
| |
| | |
| *'''Hypocalcemia'''
| |
| | |
| *Hypocalcemia has been reported in patients treated with BONIVA.
| |
| | |
| *'''Musculoskeletal Pain'''
| |
| | |
| *Bone, joint, or muscle pain (musculoskeletal pain), described as severe or incapacitating, has been reported.
| |
| | |
| *'''Jaw Osteonecrosis'''
| |
| | |
| *Osteonecrosis of the jaw has been reported in patients treated with BONIVA.
| |
| | |
| *'''Atypical Femoral Shaft Fracture'''
| |
| | |
| :*Atypical, low-energy, or low-trauma fractures of the femoral shaft.
| |
| |drugInteractions='''Calcium Supplements/Antacids'''
| |
| | |
| *Products containing calcium and other multivalent cations (such as aluminum, magnesium, iron) are likely to interfere with absorption of BONIVA. Therefore, instruct patients to take BONIVA 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 [2.3]).
| |
| | |
| '''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 BONIVA.
| |
| | |
| '''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 [12.3]).
| |
| | |
| '''Drug/Laboratory Test Interactions'''
| |
| | |
| *Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with ibandronate have not been performed.
| |
| | |
| |administration='''Dosage Information'''
| |
| | |
| *The dose of BONIVA is one 150 mg tablet taken once monthly on the same date each month.
| |
| | |
| '''Important Administration Instructions'''
| |
| | |
| Instruct Patients to do the following:
| |
| | |
| *Take BONIVA 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 [7.1]). Avoid the use of water with supplements including mineral water because they may have a higher concentration of calcium.
| |
| *Swallow BONIVA 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 BONIVA. 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 BONIVA.
| |
| | |
| '''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 BONVIA administration because co-administration of BONIVA and calcium may interfere with the absorption of ibandronate sodium.
| |
| | |
| '''Administration Instructions for Missed Once-Monthly Doses'''
| |
| | |
| *If the once-monthly dose is missed, instruct patients to do the following:
| |
| | |
| :*If the next scheduled BONIVA day is more than 7 days away, take one BONIVA 150 mg tablet in the morning following the date that it is remembered.
| |
| :*If the next scheduled BONIVA day is only 1 to 7 days away, wait until the subsequent month's scheduled BONIVA day to take their tablet.
| |
| | |
| *For subsequent monthly doses for both of the above scenarios, instruct patients to return to their original schedule by taking one BONIVA 150 mg tablet every month on their previous chosen day.
| |
| | |
| '''DOSAGE FORMS AND STRENGTHS'''
| |
| | |
| *BONIVA 150 mg tablets: white, oblong, engraved with "BNVA" on one side and "150" on the other side.
| |
| |alcohol=Alcohol-Ibandronic acid interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
| |
| }}
| |