Active ingredient: Ibandronic acid, monosodium salt, monohydrate. One 150 mg film-coated tablet contains 168.79 mg of ibandronic sodium monohydrate equivalent to 150 mg of ibandronic acid.
Therapeutic/Pharmacologic Class of Drug: Ibonate is a nitrogen containing bisphosphonate.
Pharmacology: Pharmacodynamics: The pharmacodynamic action of ibandronic acid is inhibition of bone resorption.
Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity. It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone.
Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass.
Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.
Pharmacokinetics: The pharmacological effects of ibandronic acid are not directly related to actual plasma concentrations. This was demonstrated by various studies in animals and in humans, in which equivalent efficacy of ibandronic acid was demonstrated following either daily or intermittent regimens, consisting of a drug-free interval of several weeks (at least 6 weeks in rats, at least 11 weeks in dogs, at least 30 days in monkeys, and at least 9.5 weeks in humans) provided the same total dose was administered over this period.
Absorption: The absorption of ibandronic acid in the upper gastrointestinal tract is rapid after oral administration and plasma concentrations increase in a dose-proportional manner up to 50 mg oral intake, with greater than dose-proportional increases seen above this dose. Maximum observed plasma concentration were reached within 0.5 to 2 hours (median 1 hour) in the fasted state and absolute bioavailability was about 0.6%. The extent of absorption is impaired when taken together with food or beverages (other plain water). Bioavailability is reduced by about 90% when ibandronic acid is administered with a standard breakfast in comparison with bioavailability seen in fasted subjects. There is no meaningful reduction in bioavailability provided ibandronic acid is taken 60 minutes before a meal.
Both bioavailability and BMD gains are reduced when food or beverage are taken less than 60 minutes after ibandronic acid.
Distribution: After initial systemic exposure, ibandronic acid rapidly binds to bone or is excreted into urine. In humans, the apparent terminal volume of distribution is at least 90 l and the amount of dose reaching the bone is estimated to be 40-50% of the circulating dose. Protein binding in human plasma is low (approximately 85% bound at therapeutic concentrations), and thus there is a low potential for drug-drug interaction due to displacement.
Metabolism: There is no evidence that ibandronic acid is metabolized in animals or humans.
Elimination: The absorbed fraction of ibandronic acid is removed from the circulation via bone absorption (40-50%) and the remainder is eliminated unchanged by the kidney. The unabsorbed fraction of ibandronic acid is eliminated unchanged in the feces. The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the apparent terminal half-life is generally in the range of 10-72 hours. Early plasma levels fall quickly reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration respectively.
Total clearance of ibandronic acid is low with average values in the range 84-160 ml/min. Renal clearance (about 60 ml/min in healthy postmenopausal females) accounts for 50-60% of total clearance and is related to creatinine clearance. The difference between the apparent total and renal clearances is considered to reflect the uptake by bone.
Phamacokinetics in Special Populations: Gender: Bioavailability and pharmacokinetics of ibandronic acid are similar in both men and women.
Race: There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in ibandronic acid disposition. There are few data available on patients of African origin.
Patients with renal impairment: Renal clearance of ibandronic acid in patients with various degrees of renal impairment is linearly related to creatinine clearance (CLcr).
No dosage adjustment is necessary for patients with mild or moderate renal impairment (CLcr ml/min).
Patients with hepatic impairment: There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment. The liver has no significant role in the clearance of ibandronic acid which is not metabolized but is cleared by renal excretion and by uptake into bone. Therefore, dosage adjustment is not necessary in patients with hepatic impairment. Further, as protein binding of ibandronic acid is low (85%) at therapeutic concentrations, hypoproteinemia in severe liver disease is unlikely to lead to clinically significant increases in free plasma concentration.
Elderly: In a multivariate analysis age was not found to be an independent factor of any of the pharmacokinetic parameters studied. As renal function decreases with age, this is the only factor to take into consideration (see Patients with renal impairment, as mentioned in the previous text).
Children: There are no data on the use of Ibonate in patients less than 18 years old.
Ibonate 150 mg is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.
The recommended dose of Ibonate for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibonate should be taken 60 minutes before the first food or drink (other than water) of the day (see Interactions) or any other oral medication of supplementation (including calcium): Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting of or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibonate.
Plain water is the only drink that should be taken with Ibonate. 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 Ibonate 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.
Special Dosage Instructions: Patients with hepatic impairment: No dosage adjustment is necessary (see Pharmacology: Pharmacokinetics under Actions).
Patients with renal impairment: No dosage adjustment is necessary for patients with mild or moderate renal impairment where creatinine clearance ≥ 30 ml/min.
Below 30 ml/min creatinine clearance, the decision to administer Ibonate should be based on an individual risk benefit assessment (see Pharmacology: Pharmacokinetics under Actions).
Elderly: No dosage adjustment is necessary.
Children: Safety and efficacy have not been established in patients less than 18 years old.
No specific information is available on the treatment of overdosage with Ibonate. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind Ibonate. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.
Ibonate is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients.
Ibonate 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 Ibonate. As with several bisphosphonates, Ibonate is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture of achalasia (see Precautions). Ibonate is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes (see Dosage & Administration and Precautions).
General: Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibonate 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 Ibonate 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 Dosage and Administration).
Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibonate 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 reports 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 Ibonate.
Osteonecrosis of the jaw 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 Osteonecrosis of the jaw. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.
Effects on ability to drive and use machinery: No studies on the effects on the ability to drive and use machines have been performed.
Hepatic and Renal impairment: See Pharmacology: Pharmacokinetics under Actions.
Use in Children: See Pharmacology: Pharmacokinetics under Actions.
Use in the Elderly: See Pharmacology: Pharmacokinetics under Actions.
Use in Pregnancy: Ibonate 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 Ibonate in pregnant women.
Use in Lactation: Ibonate should not be used during lactation.
In lactating rats treated with 0.08 mg/kg/day i.v. 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.
It is not known whether Ibonate is excreted in human milk.
Gastrointestinal system: Gastro-oesophageal reflux disease, diarrhoea, abdominal pain, dyspepsia, nausea, flatulence, gastritis, oesophagitis (including oesophageal ulcerations or strictures), duodenitis.
Nervous system: Headache, dizziness.
Musculoskeletal system: Arthralgia, myalgia, back pain.
Skin and Subcutaneous Tissue Disorders: Angioedema, face oedema, urticaria, rash.
Immune System Disorders: Hypersensitivity reactions.
General disorders: Fatigue, influenza like illness (including myalgia, arthralgia, fever, chills, fatigue, nausea, loss of appetite, or bone pain).
Eye disorders: Ocular inflammation events such as uveitis, episcleritis and scleritis.
Drug-Food Interactions: Products containing calcium and other multivalent cations (such as aluminium, magnesium, iron), including milk and food, are likely to interfere with absorption of Ibonate which is consistent with findings in animal studies. Therefore, with such products, including food, intake must be delayed for 60 minutes following oral administration.
Drug-Drug Interactions: It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibonate. Therefore, patients must wait 60 minutes after taking Ibonate before taking other oral medications.
Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma.
In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20%, probably as a result of reduced gastric acidity. However, since this increase the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibonate is administered with H2-antagonists or other drugs which increase gastric pH.
In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs.
Special Instructions for Use, Handling and Disposal: Disposal of unused/expired medicines: The release of pharmaceuticals in the environment should be minimized. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Use established "collection systems" if available in the location.
M05BA06 - ibandronic acid ; Belongs to the class of bisphosphonates. Used in the treatment of bone diseases.
Ibonate FC tab 150 mg
1's
Sign Out
