Generic

Ibandronic acid

Therapeutic Class

Bone Calcium Regulator

Pack Size

Bonova 150 mg tablet: Each box contains 1 tablet (1 x 1's) in Alu-PVC / PVDC blister pack.

Indications

Bonova 150 mg is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures. Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score < -2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Therapeutic Class

Bone Calcium Regulator

Dosage & Administration

The recommended dose of Bonova for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Bonova should be taken 60 minutes before the first food or drink (other than water) of the day (see section 2.4.3 Interactions with other Medicinal Products and other Forms of Interaction, Drug-Food Interactions) or any other oral medication or supplementation (including calcium): — Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Bonova. — Plain water is the only drink that should be taken with Bonova. 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. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Bonova 150 mg tablet the morning after the tablet is remembered, unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

Contraindications

Bonova is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Bonova is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Bonova. As with several bisphosphonates, Bonova is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia (see section 2.4 Warnings and Precautions). Bonova is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes (see sections 2.2 Dosage and Administration and 2.4 Warnings and Precautions).

Side Effects

Treatment of postmenopausal osteoporosis Once-monthly dosing In a two-year study in postmenopausal women with osteoporosis (BM 16549) the overall safety of Bonova 150 mg once monthly and Bonova 2.5 mg daily was similar. The overall proportion of patients who experienced an adverse drug reaction, i.e. adverse event with a possible or probable relationship to trial medication, was 22.7 % and 25.0 % for Bonova 150mg once monthly and 21.5 % and 22.5 % for Bonova 2.5 mg daily after one and two years, respectively. The majority of adverse drug reactions were mild to moderate in intensity. Most cases did not lead to cessation of therapy. Clinical Trials Treatment of postmenopausal osteoporosis Once-monthly dosing In a two-year study in postmenopausal women with osteoporosis (BM 16549) the overall safety of Bonova 150 mg once monthly and Bonova 2.5 mg daily was similar. The overall proportion of patients who experienced an adverse drug reaction, i.e. adverse event with a possible or probable relationship to trial medication, was 22.7 % and 25.0 % for Bonova 150mg once monthly and 21.5 % and 22.5 % for Bonova 2.5 mg daily after one and two years, respectively. The majority of adverse drug reactions were mild to moderate in intensity. Most cases did not lead to cessation of therapy. Tables 1 and 2 list adverse drug reactions occurring in more than I % of patients treated with Bonova 150 mg monthly or 2.5 mg daily in study BM 16549 and in patients treated with Bonova 2.5 mg daily in study MF 4411. The tables show the adverse drug reactions in the two studies that occurred with a higher incidence than in patients treated with placebo in study MF 4411. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Data at one year from BM 16549 are represented in Table 1 and cumulative data for the two years from BM 16549 are represented in Table 2. Adverse drug reactions occurring at a frequency of less than or equal to 1 % The following list provides information on adverse drug reactions (considered possibly or probably related to treatment by the investigator) reported in study MF 4411 occurring more frequently with Bonova 2.5 mg daily than with placebo and study BM 16549 occurring more frequently with Bonova 150 mg once monthly than with Bonova 2.5 mg daily. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: Uncommon (1/100 — 1/1,000) Gastrointestinal Disorders: gastritis, oesophagitis including oesophageal ulcerations or strictures, vomiting, dysphagia Nervous System Disorders: dizziness Musculoskeletal and Connective Tissue Disorders: back pain Rare (1/1,000 — 1/10,000) Gastrointestinal Disorders: duodenitis Immune System Disorders: hypersensitivity reactions Skin and Subcutaneous Tissue Disorders: angioedema, face oedema, urticaria Patients with a previous history of gastrointestinal disease including patients with peptic ulcer without recent bleeding or hospitalisation, 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 the incidence of upper gastrointestinal adverse events with the 150 mg once monthly regimen compared to the 2.5 mg daily regimen. Laboratory Abnormalities In the pivotal three-year study with Bonova 2.5 mg daily (MF 4411) there was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, impaired hematologic system, hypocalcemia or hypophosphatemia. Similarly, no differences were noted between the groups in study BM 16549 after one and two years. Post Marketing Musculoskeletal and connective tissue disorders: Osteonecrosis of the jaw has been reported very rarely in patients treated with ibandronic acid (refer to 2.4 Warnings and Precautions). Eye disorders: Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with bisphosphonates, including ibandronic acid. In some cases, these events did not resolve until the bisphosphonate was discontinued.

Pregnancy & Lactation

In pregnancy: Bonova should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Bonova in pregnant women. In lactation: Bonova should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day iv. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

Precautions

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Bonova therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates 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 Bonova is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions (see section 2.2 Dosage and Administration). Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Bonova and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing eports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Bonova. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

Storage Conditions

Keep in a cool and dry place. Do not store above 30°C. Keep out of reach of children.