BONIVA^®
(ibandronate sodium)
TABLETS

BONIVA (ibandronate sodium) is a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption. The chemical name for ibandronate sodium is 3-(N-methyl-N-pentyl) amino-1-hydroxypropane-1,1-diphosphonic acid, monosodium salt, monohydrate with the molecular formula C₉H₂₂NO₇P₂Na•H₂O and a molecular weight of 359.24. Ibandronate sodium is a white- to off-white powder. It is freely soluble in water and practically insoluble in organic solvents. Ibandronate sodium has the following structural formula:

BONIVA is available as a white, oblong, 2.5-mg film-coated tablet for daily oral administration or as a white, oblong, 150-mg film-coated tablet for once-monthly oral administration. One 2.5-mg film-coated tablet contains 2.813 mg ibandronate monosodium monohydrate, equivalent to 2.5 mg free acid. One 150-mg film-coated tablet contains 168.75 mg ibandronate monosodium monohydrate, equivalent to 150 mg free acid. BONIVA also contains the following inactive ingredients: lactose monohydrate, povidone, microcrystalline cellulose, crospovidone, purified stearic acid, colloidal silicon dioxide, and purified water. The tablet film coating contains hypromellose, titanium dioxide, talc, polyethylene glycol 6000, and purified water.

The action of ibandronate on bone tissue is based on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Ibandronate inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

Ibandronate does not undergo hepatic metabolism and does not inhibit the hepatic cytochrome P450 system. Ibandronate is eliminated by renal excretion. Based on a rat study, the ibandronate secretory pathway does not appear to include known acidic or basic transport systems involved in the excretion of other drugs.

Products containing calcium and other multivalent cations (such as aluminum, magnesium, iron), including milk, food, and antacids are likely to interfere with absorption of ibandronate, which is consistent with findings in animal studies.

Osteoporosis is characterized by decreased bone mass and increased fracture risk, most commonly at the spine, hip, and wrist. The diagnosis can be confirmed by a finding of low bone mass, evidence of fracture on x-ray, a history of osteoporotic fracture, or height loss or kyphosis indicative of vertebral fracture. While osteoporosis occurs in both men and women, it is most common among women following menopause. In healthy humans, bone formation and resorption are closely linked; old bone is resorbed and replaced by newly formed bone. In postmenopausal osteoporosis, bone resorption exceeds bone formation, leading to bone loss and increased risk of fracture. After menopause, the risk of fractures of the spine and hip increases; approximately 40% of 50-year-old women will experience an osteoporosis-related fracture during their remaining lifetimes.

BONIVA produced biochemical changes indicative of dose-dependent inhibition of bone resorption, including decreases of biochemical markers of bone collagen degradation (such as deoxypyridinoline, and cross-linked C-telopeptide of Type I collagen) in the daily dose range of 0.25 to 5.0 mg and once-monthly doses from 100 mg to 150 mg in postmenopausal women.

Treatment with 2.5 mg daily BONIVA resulted in decreases in biochemical markers of bone turnover, including urinary C-terminal telopeptide of Type I collagen (uCTX) and serum osteocalcin, to levels similar to those in premenopausal women. Changes in markers of bone formation were observed later than changes in resorption markers, as expected, due to the coupled nature of bone resorption and formation. Treatment with 2.5 mg daily BONIVA decreased levels of uCTX within 1 month of starting treatment and decreased levels of osteocalcin within 3 months. Bone turnover markers reached a nadir of approximately 64% below baseline values by 6 months of treatment and remained stable with continued treatment for up to 3 years. Following treatment discontinuation, there is a return to pretreatment baseline rates of elevated bone resorption associated with postmenopausal osteoporosis.

In a 1-year, Phase 3 study comparing once-monthly vs. once-daily oral dosing regimens, the median decrease from baseline in serum CTX values was -76% for patients treated with the 150 mg once-monthly regimen and -67% for patients treated with the 2.5 mg daily regimen.

The effectiveness and safety of BONIVA 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 [L1-L4], and who had 1 to 4 prevalent vertebral fractures. BONIVA was 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 IU vitamin D and 500 mg calcium supplementation per day.

The effectiveness and safety of BONIVA 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-L4 lumbar spine BMD T-score below -2.5 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 IU vitamin D and 500 mg calcium supplementation per day.

BONIVA 2.5 mg daily prevented bone loss in a majority of women 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 >-2.5. Women were stratified according to time since menopause (1 to 3 years, >3 years) and baseline lumbar spine BMD (T-score: >-1, -1 to -2.5). The study compared daily BONIVA 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. BONIVA 2.5 mg daily resulted in a mean increase in lumbar spine BMD of 3.1% compared with placebo following 2 years of treatment (see Figure 1). 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 BONIVA resulted in a higher BMD response at the lumbar spine compared with placebo across all four baseline strata [time since menopause (1 to 3 years, >3 years) and baseline lumbar spine BMD (T-score: >-1, -1 to -2.5)].

Compared with placebo, treatment with BONIVA 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% (see Figure 1).

Figure 1 Mean Percentage Change in BMD from Baseline to Endpoint in Patients Treated with BONIVA 2.5 mg or Placebo in the 2-Year Osteoporosis Prevention Study*

*The endpoint value is the value at the study's last time point, 2 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
**Lumbar spine BMD p<0.001 vs. placebo.

The safety and efficacy of once-monthly BONIVA 150 mg in postmenopausal women without osteoporosis are currently being studied, but data are not yet available.

Animal studies have shown that ibandronate is an inhibitor of osteoclast-mediated bone resorption. In the Schenk assay in growing rats, ibandronate inhibited bone resorption and increased bone volume, based on histologic examination of the tibial metaphyses. There was no evidence of impaired mineralization at the highest dose of 5 mg/kg/day (subcutaneously), which is 1000 times the lowest antiresorptive dose of 0.005 mg/kg/day in this model, and 5000 times the optimal antiresorptive dose of 0.001 mg/kg/day in the aged ovariectomized rat. This indicates that BONIVA administered at therapeutic doses is unlikely to induce osteomalacia.

Long-term daily or once-monthly intermittent administration of ibandronate to ovariectomized rats or monkeys was associated with suppression of bone turnover and increases in bone mass. In both rats and monkeys, vertebral BMD, trabecular density, and biomechanical strength were increased dose-dependently at doses up to 15 times the recommended human daily oral dose of 2.5 mg, or cumulative monthly doses up to 8 times (rat) or 6 times (monkey) the recommended human once-monthly oral dose of 150 mg, based on body surface area (mg/m²) or AUC comparison. In monkeys, ibandronate maintained the positive correlation between bone mass and strength at the ulna and femoral neck. New bone formed in the presence of ibandronate had normal histologic structure and did not show mineralization defects.

BONIVA is indicated for the treatment and prevention of osteoporosis in postmenopausal women.

In postmenopausal women with osteoporosis, BONIVA increases BMD and reduces the incidence of vertebral fractures (see CLINICAL STUDIES). Osteoporosis may be confirmed by the presence or history of osteoporotic fracture or by a finding of low bone mass (BMD more than 2 standard deviations below the premenopausal mean [ie, T-score]).

BONIVA may be considered in postmenopausal women who are at risk of developing osteoporosis and for whom the desired clinical outcome is to maintain bone mass and to reduce the risk of fracture.

Factors such as family history of osteoporosis, early menopause, previous fracture, high bone turnover, reduced BMD (at least 1.0 SD below the premenopausal mean), thin body frame, Caucasian or Asian race, and smoking, are associated with an increased risk of developing osteoporosis and fractures. The presence of these risk factors may be important when considering the use of BONIVA for preventing osteoporosis.

• Known hypersensitivity to BONIVA or to any of its excipients
• Uncorrected hypocalcemia (see PRECAUTIONS: General)
• Inability to stand or sit upright for at least 60 minutes (see DOSAGE AND ADMINISTRATION)

BONIVA, like other bisphosphonates administered orally may cause upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer (see PRECAUTIONS).

Patients should be instructed to read the Patient Information Leaflet carefully before taking BONIVA, to re-read it each time the prescription is renewed and to pay particular attention to the dosing instructions in order to maximize absorption and clinical benefit.

• -BONIVA should be taken at least 60 minutes before the first food or drink (other than water) of the day and before taking any oral medication or supplementation including calcium, antacids or vitamins (see Drug Interactions: Calcium Supplements/Antacids).
• -To facilitate delivery to the stomach, and thus reduce the potential for esophageal irritation, BONIVA tablets should be swallowed whole with a full glass of plain water (6 to 8 oz) while the patient is standing or sitting in an upright position. Patients should not lie down for 60 minutes after taking BONIVA.
• -Plain water is the only drink that should be taken with BONIVA. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• -Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration.
• -The BONIVA 150-mg tablet should be taken on the same date each month (ie, the patient's BONIVA day).
• -If the once-monthly dose is missed, and the patient's next scheduled BONIVA day is more than 7 days away, the patient should be instructed to take one BONIVA 150-mg tablet in the morning following the date that it is remembered (see DOSAGE AND ADMINISTRATION). The patient should then return to taking one BONIVA 150-mg tablet every month in the morning of their chosen day, according to their original schedule.
• -The patient must not take two 150-mg tablets within the same week. If the patient's next scheduled BONIVA day is only 1 to 7 days away, the patient must wait until their next scheduled BONIVA day to take their tablet. The patient should then return to taking one BONIVA 150-mg tablet every month in the morning of their chosen day, according to their original schedule.

Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate. Intake of supplemental calcium and vitamin D should be delayed for at least 60 minutes following oral administration of BONIVA in order to maximize absorption of BONIVA.

Physicians should be alert to signs or symptoms signaling a possible esophageal reaction during therapy, and patients should be instructed to discontinue BONIVA and seek medical attention if they develop symptoms of esophageal irritation such as new or worsening dysphagia, pain on swallowing, retrosternal pain, or heartburn.

See CLINICAL PHARMACOLOGY: Pharmacokinetics: Drug Interactions.

Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with ibandronate have not been performed.

In lactating rats treated with intravenous doses of 0.08 mg/kg, ibandronate was present in breast milk at concentrations of 8.1 to 0.4 ng/mL from 2 to 24 hours after dose administration. Concentrations in milk averaged 1.5 times plasma concentrations. It is not known whether BONIVA is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BONIVA is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

Of the patients receiving BONIVA 2.5 mg daily in postmenopausal osteoporosis studies, 52% were over 65 years of age, and 10% were over 75 years of age. Of the patients receiving BONIVA 150 mg once monthly in the postmenopausal osteoporosis 1-year study, 52% were over 65 years of age, and 9% were over 75 years of age. No overall differences in effectiveness or safety were observed between these patients and younger patients but greater sensitivity in some older individuals cannot be ruled out.

Daily treatment with oral BONIVA was studied in over 3900 patients in postmenopausal osteoporosis trials of up to 3 years duration. The overall adverse event profile of BONIVA 2.5 mg once daily in these studies was similar to that of placebo.

Most adverse events were mild or moderate and did not lead to discontinuation. The incidence of serious adverse events 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 events was approximately 17% in both the BONIVA 2.5 mg daily group and the placebo group. Overall, and according to body system, there was no difference between BONIVA and placebo, with adverse events of the digestive system being the most common reason for withdrawal.

Table 3 uls adverse events from the Treatment and Prevention Studies reported in ≥2% of patients and in more patients treated daily with BONIVA than patients treated with placebo. Adverse events are shown without attribution of causality.

In a 1-year, double-blind, multicenter study comparing BONIVA 2.5 mg once daily and BONIVA 150 mg once monthly in women with postmenopausal osteoporosis, the overall safety and tolerability profiles of the two oral dosing regimens were similar. The incidence of serious adverse events was 4.8% in the BONIVA 2.5 mg daily group and 7.1% in the BONIVA 150 mg once-monthly group. The percentage of patients who withdrew from treatment due to adverse events was approximately 8.9% in the BONIVA 2.5 mg daily group and 7.8% in the BONIVA 150 mg once-monthly group. Table 4 uls the adverse events reported in ≥2% of patients without attribution of causality.

Patients with a previous history of gastrointestinal disease, including patients with peptic ulcer without recent bleeding or hospitalization and patients with dyspepsia or reflux controlled by medication, were included in the once-monthly treatment study. For these patients, there was no difference in upper gastrointestinal adverse events with the 150 mg once-monthly regimen compared to the 2.5 mg once-daily regimen.

Reports in the medical literature indicate that bisphosphonates may be associated with ocular inflammation such as uveitis 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. Two patients who received BONIVA once monthly experienced ocular inflammation, one was a case of uveitis and the other scleritis.

In the 3-year treatment study with BONIVA 2.5 mg daily, there were no clinically significant changes from baseline values or shifts in any laboratory variable for each of the treatment groups. As expected with bisphosphonate treatment, a decrease in total alkaline phosphatase levels was seen in the active treatment groups compared to placebo. There was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, hypocalcemia, or hypophosphatemia. Similarly, no changes were noted for the 150 mg once-monthly administration in the 1-year study.

No specific information is available on the treatment of overdosage with BONIVA. 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 BONIVA. Due to the risk of esophageal irritation, vomiting should not be induced, and the patient should remain fully upright. Dialysis would not be beneficial.

The recommended dose of BONIVA for treatment of postmenopausal osteoporosis is one 2.5-mg tablet taken once daily or one 150-mg tablet taken once monthly on the same date each month (see INDICATIONS AND USAGE).

The recommended dose of BONIVA for the prevention of postmenopausal osteoporosis is one 2.5-mg tablet taken once daily. Alternatively, one 150-mg tablet taken once monthly on the same date each month may be considered (see INDICATIONS AND USAGE).

• -To maximize absorption and clinical benefit, BONIVA should be taken 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 (see PRECAUTIONS: Information for Patients and Drug Interactions).
• -To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation, BONIVA tablets should be swallowed whole with a full glass of plain water (6 to 8 oz) while the patient is standing or sitting in an upright position. Patients should not lie down for 60 minutes after taking BONIVA (see PRECAUTIONS: General and Information for Patients).
• -Plain water is the only drink that should be taken with BONIVA. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• -Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration.
• -The BONIVA 150-mg tablet should be taken on the same date each month (ie, the patient's BONIVA day).
• - If the once-monthly dose is missed, and the patient's next scheduled BONIVA day is more than 7 days away, the patient should be instructed to take one BONIVA 150-mg tablet in the morning following the date that it is remembered. The patient should then return to taking one BONIVA 150-mg tablet every month in the morning of their chosen day, according to their original schedule.
• -The patient must not take two 150-mg tablets within the same week. If the patient's next scheduled BONIVA day is only 1 to 7 days away, the patient must wait until their next scheduled BONIVA day to take their tablet. The patient should then return to taking one BONIVA 150-mg tablet every month in the morning of their chosen day, according to their original schedule.

Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see PRECAUTIONS: Information for Patients).

No dose adjustment is necessary (see CLINICAL PHARMACOLOGY: Special Populations).

No dose adjustment is necessary for patients with mild or moderate renal impairment where creatinine clearance is equal to or greater than 30 mL/min.

BONIVA is not recommended for use in patients with severe renal impairment (creatinine clearance of <30 mL/min) (see CLINICAL PHARMACOLOGY: Special Populations).

No dosage adjustment is necessary in the elderly (see PRECAUTIONS: Geriatric Use).

BONIVA 2.5-mg tablets: supplied as white, oblong, film-coated tablets, engraved with "IT" on one side and "L3" on the other side and packaged in bottles of 30 tablets (NDC 0004-0185-23).

BONIVA 150-mg tablets: supplied as white, oblong, film-coated tablets, engraved with "BNVA" on one side and "150" on the other side. Packaged in boxes of 3 buler packs containing 1 tablet each (NDC 0004-0186-82).

Store at 25°C (77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature].

Read this patient information carefully before you start taking BONIVA. Read this patient information each time you get a refill for BONIVA. There may be new information. This information is not everything you need to know about BONIVA. It does not take the place of talking with your health care provider about your condition or your treatment. Talk about BONIVA with your health care provider before you start taking it, and at your regular check-ups.

What is the most important information I should know about BONIVA?

BONIVA may cause serious problems in the stomach and the esophagus (the tube that connects your mouth and stomach) such as trouble swallowing, heartburn, and ulcers (see "What are the possible side effects of BONIVA?").

You must take BONIVA exactly as prescribed for BONIVA to work for you and to lower the chance of serious side effects (see "How should I take BONIVA?").

What is BONIVA?

BONIVA is a prescription medicine used to treat or prevent osteoporosis in women after menopause (see the end of this leaflet for "What is osteoporosis?").

BONIVA may reverse bone loss by stopping more loss of bone and increasing bone mass in most women who take it, even though they won't be able to see or feel a difference. BONIVA may help lower the chances of breaking bones (fractures).

For BONIVA to treat or prevent osteoporosis, you have to take it as prescribed. BONIVA will not work if you stop taking it.

Who should not take BONIVA?

Do not take BONIVA if you:

• have low blood calcium (hypocalcemia)
• cannot sit or stand up for at least 1 hour (60 minutes)
• have kidneys that work very poorly
• are allergic to ibandronate sodium or any of the other ingredients of BONIVA (see the end of this leaflet for a ul of all the ingredients in BONIVA)

Tell your health care provider before using BONIVA:

• if you are pregnant or planning to become pregnant. It is not known if BONIVA can harm your unborn baby.
• if you are breast-feeding. It is not known if BONIVA passes into your milk and if it can harm your baby.
• have swallowing problems or other problems with your esophagus (the tube that connects your mouth and stomach)
• if you have kidney problems
• if you are planning a dental procedure such as tooth extraction

Tell your health care provider (including your dentist) about all the medicines you take including prescription and non-prescription medicines, vitamins and supplements. Some medicines, especially certain vitamins, supplements, and antacids can stop BONIVA from getting to your bones. This can happen if you take other medicines too close to the time that you take BONIVA (see "How should I take BONIVA?").

How should I take BONIVA?

• Take BONIVA exactly as instructed by your health care provider.
• Take BONIVA first thing in the morning at least 1 hour (60 minutes) before you eat, drink anything other than plain water, or take any other oral medicine.
• Take BONIVA with 6 to 8 ounces (about 1 full cup) of plain water. Do not take it with any other drink besides plain water. Do not take it with other drinks, such as mineral water, sparkling water, coffee, tea, dairy drinks (such as milk), or juice.
• Swallow BONIVA whole. Do not chew or suck the tablet or keep it in your mouth to melt or dissolve.
• After taking BONIVA you must wait at least 1 hour (60 minutes) before:
  • –Lying down. You may sit, stand, or do normal activities like read the newspaper or take a walk.
  • –Eating or drinking anything except for plain water.
  • –Taking other oral medicines including vitamins, calcium, or antacids. Take your vitamins, calcium, and antacids at a different time of the day from the time when you take BONIVA.
• If you take too much BONIVA, drink a full glass of milk and call your local poison control center or emergency room right away. Do not make yourself vomit. Do not lie down.
• Keep taking BONIVA for as long as your health care provider tells you. BONIVA will not work if you stop taking it.
• Your health care provider may tell you to exercise and take calcium and vitamin supplements to help your osteoporosis.
• Your health care provider may do a test to measure the thickness (density) of your bones or do other tests to check your progress.

What is my BONIVA schedule?

Schedule for taking BONIVA 150 mg once monthly:

• Take one BONIVA 150-mg tablet once a month.
• Choose one date of the month (your BONIVA day) that you will remember and that best fits your schedule to take your BONIVA 150-mg tablet.
• Take one BONIVA 150-mg tablet in the morning of your chosen day (see "How should I take BONIVA?").

What to do if I miss a monthly dose:

• If your next scheduled BONIVA day is more than 7 days away, take one BONIVA 150-mg tablet in the morning following the day that you remember (see "How should I take BONIVA?"). Then return to taking one BONIVA 150-mg tablet every month in the morning of your chosen day, according to your original schedule.
• Do not take two 150-mg tablets within the same week. If your next scheduled BONIVA day is only 1 to 7 days away, wait until your next scheduled BONIVA day to take your tablet. Then return to taking one BONIVA 150-mg tablet every month in the morning of your chosen day, according to your original schedule.
• If you are not sure what to do if you miss a dose, contact your health care provider who will be able to advise you.

Schedule for taking BONIVA 2.5 mg once daily:

• Take one BONIVA 2.5-mg tablet once a day first thing in the morning at least 1 hour (60 minutes) before you eat, drink anything other than plain water, or take any other oral medicine (see "How should I take BONIVA?").

What to do if I miss a daily dose:

• If you forget to take your BONIVA 2.5-mg tablet in the morning, do not take it later in the day. Just return to your normal schedule and take 1 tablet the next morning. Do not take two tablets on the same day.
• If you are not sure what to do if you miss a dose, contact your health care provider who will be able to advise you.

What should I avoid while taking BONIVA?

• Do not take other medicines, or eat or drink anything but plain water before you take BONIVA and for at least 1 hour (60 minutes) after you take it.
• Do not lie down for at least 1 hour (60 minutes) after you take BONIVA.

What are the possible side effects of BONIVA?

Stop taking BONIVA and call your health care provider right away if you have:

• pain or trouble with swallowing
• chest pain
• very bad heartburn or heartburn that does not get better

BONIVA MAY CAUSE:

• pain or trouble swallowing (dysphagia)
• heartburn (esophagitis)
• ulcers in your stomach or esophagus (the tube that connects your mouth and stomach)

Common side effects with BONIVA are:

• diarrhea
• pain in extremities (arms or legs)
• dyspepsia (upset stomach)

Less common side effects with BONIVA are short-lasting, mild flu-like symptoms (usually improve after the first dose). These are not all the possible side effects of BONIVA. For more information ask your health care provider or pharmacist.

Rarely, patients have reported severe bone, joint, and/or muscle pain starting within one day to several months after beginning to take, by mouth, bisphosphonate drugs to treat osteoporosis (thin bones). This group of drugs includes BONIVA. Most patients experienced relief after stopping the drug. Contact your health care provider if you develop these symptoms after starting BONIVA.

Rarely, patients taking bisphosphonates have reported serious jaw problems associated with delayed healing and infection, often following dental procedures such as tooth extraction. If you experience jaw problems, please contact your health care provider and dentist.

What is osteoporosis?

Osteoporosis is a disease that causes bones to become thinner. Thin bones can break easily. Most people think of their bones as being solid like a rock. Actually, bone is living tissue, just like other parts of the body, such as your heart, brain, or skin. Bone just happens to be a harder type of tissue. Bone is always changing. Your body keeps your bones strong and healthy by replacing old bone with new bone.

Osteoporosis causes the body to remove more bone than it replaces. This means that bones get weaker. Weak bones are more likely to break. Osteoporosis is a bone disease that is quite common in women after menopause. At first, osteoporosis has no symptoms, but people with osteoporosis may develop loss of height and are more likely to break (fracture) their bones, especially the back (spine), wrist, and hip bones.

Osteoporosis can be prevented, and with proper therapy it can be treated.

Who is at risk for osteoporosis?

Talk to your health care provider about your chances for getting osteoporosis.

Many things put people at risk for osteoporosis. The following people have a higher chance of getting osteoporosis:

Women who:

• are going through or who are past menopause ("the change")
• are white (Caucasian) or Asian

People who:

• are thin
• have a family member with osteoporosis
• do not get enough calcium or vitamin D
• do not exercise
• smoke
• drink alcohol often
• take bone thinning medicines (like prednisone) for a long time

General information about BONIVA

Medicines are sometimes prescribed for conditions that are not mentioned in patient information. Do not use BONIVA for a condition for which it was not prescribed. Do not give BONIVA to other people, even if they have the same symptoms you have. It may harm them.

Store BONIVA at 77°F (25°C) or at room temperature between 59°F and 86°F (15°C and 30°C).

Keep BONIVA and all medicines out of the reach of children.

This summarizes the most important information about BONIVA. If you would like more information, talk with your health care provider. You can ask your health care provider or pharmacist for information about BONIVA that is written for health professionals.

For more information about BONIVA, call 1-888-MY-BONIVA or visit www.myboniva.com.

What are the ingredients of BONIVA?

BONIVA (active ingredient): ibandronate sodium

BONIVA (inactive ingredients): lactose monohydrate, povidone, microcrystalline cellulose, crospovidone, purified stearic acid, colloidal silicon dioxide, and purified water. The tablet film coating contains hypromellose, titanium dioxide, talc, polyethylene glycol 6000 and purified water.