Alendronate

COMPOSITION:

Bone med 10mg: Each tablet contains Alendronate sodium triyhdrate equivalent to 10mg Alendronate acid USP

Bone med 70mg: Each tablet contains Alendronate sodium triyhdrate equivalent to 70mg Alendronate acid USP

DESCRIPTION:

Alendronate sodium is chemically described as (4-amino-1-hydroxybutylidene) biphosphonic acid monosodium triyhdrate. The empirical formula is C4H12NNaO7P2 and its formula weight is 325.12

Alendronate is a white, crystalline, non-hygroscopic powder; it is soluble in water, very slightly soluble in alcohol, and practically insoluble in chloroform.

CLINICAL PHARMACOLOGY:

Alendronate sodium acts as a specific inhibitor of osteoclastmediated bone resorption.

Mode of Action

At the cellular level, Alendronate sodium shows preferential localization to sites of bone resorption, specifically under osteoclassis, Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclasts activity.

Studies in mice on the localization of radioactive [3H] Alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. While incorporated in bone matrix, Alendronate is not pharmacologically active, Thus, Alendronate must be continuously administered to suppress osteoclasts on newly formed resorption sites.

PHARMACOKINETICS:

Relative to an intravenous (IV) reference dose, the mean oral bioavailability of Alendronate in women was 0.64% for dose ranging from 5 to 70mg when administered after an over night fast and 2 hours before a standardized breakfast. Oral bioavailability of the 10mg tablet in men (0.59%) was similar to that in women when administered after an overnight fast and 2 hours before breakfast. Bioavailability was decreased (by approximately 40%) when 10mg Alendronate was administered either 0.5 or 1 hour before eating. In studies of treatment & prevention of osteoporosis, Alendronate was effective when administered at least 30minutes before breakfast. Bioavailability was negligible whether Alendronate was administered with or up to 2 hours after a standardized breakfast. Concomitant administration of Alendronate with coffee, or orange juice reduced Bioavailability by approximately 60%. The mean steady-state volume of distribution, exclusive of bone, is at least 28L. In humans Concentration of drug in plasma following therapeutic oral doses are too low (less than 5mg/ml) for analytical detection. Plasma protein binding is approximately 78%. There is no evidence that Alendronate is metabolized in animals or humans.

Following a single IV dose of [14C] Alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces. Following a single 10mg IV dose, the renal clearance of Alendronate was 71ml/min. and systemic clearance did not exceed 200ml/min. Plasma concentration fell by more than 95% within 6 hours following IV administration.

Alendronate pharmacokinetics have not been investigated in patients<18>

Bioavailability and urinary excretion were similar in elderly & younger patients. No dosage adjustment is necessary (see DOSAGE & ADMINISTRATION). Although no clinical information is available, it is likely that elimination of Alendronate via Kidneys will be reduced in patients with impaired renal function. No dosage adjustment is necessary for patients with mild to moderate renal insufficiency (creatinine clearance 35 to 60ml/min) no dosage adjustment is necessary in patients with hepatic insufficiency as Alendronate is not metabolized or excreted in the bile.

INDICATIONS & USAGE:

BONEMED is indicated for:

- Treatment & prevention of osteoporosis in postmenopausal women.

-For the treatment of osteoporosis, BONEMED increases bone mass and reduce the incidence of fractures, including those of the hip & spine.

- For the prevention of osteoporosis, BONEMED may be considered in postmenopausal women who are at risk of developing osteoporosis & for whom the desired clinical out come is to maintain bone mass and to reduce the risk of future fractures.

- Treatment to increase bone mass in men with osteoporosis.

- Treatment of glucocorticoid-induced osteoporosis in men & women receiving glucocorticoids in a daily dosage equivalent to 7.5mg or greater of prednisone & who have low bone mineral density.

- Treatment of Paget’s disease in bone in men and women.

CONTRA-INDICATIONS:

- Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia.

- Inability to stand or sit upright for at least 30 minutes.

- Hypersensivity to any component of the product Hypocalcaemia.

ADVERSE REACTIONS:

In clinical studies of up to 5 years in duration, adverse experiences with Alendronate usually were mild, and generally did not require discontinuation of therapy. Adverse reactions experienced generally. In studies include gastro-intestinal disturbances such as acid regurgitation, flatulence, dyspepsia, abdominal pain, nausea and gastric & duodenal ulcers. Rarely rash & erythema have occurred.

PRECAUTIONS:

Hypocalcaemia must be corrected before initiating therapy with BONEMED other disturbances of mineral metabolism (such as Vit D deficiency) should also be taken into account and treated effectively. Patients treated with glucocorticoids & those suffering from Paget's disease should receive adequate amounts of Calcium & Vitamin D. Patients should be instructed to take supplemental Ca & Vit D, if daily dietary intake is inadequate.

Because of possible irritant effects on the upper gastro-intestinal mucosa & a potential for worsening of the underlying disease, caution should be used when Alendronate is given to patients with active upper gastro-intestinal problems such as dyspepsia, esophageal diseases, gastritis, duodenitis or ulcers. No data of Alendronate is available in pregnant women. BONEMED should be. Used during pregnancy only if the potential benefits outweigh potential risk to mother & fetus. It is not known whether Alendronate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BONEMED is administered in nursing women.

No overall differences in efficacy or safety were observed between geriatric and younger patients but greater sensitivity of some older individuals cannot be ruled out.

Alendronate is not recommended for patients with renal insufficiency (creatinine clearance <>

WARNINGS:

Alendronate, like other biphosphonates, may cause local irritation of the upper gastro-intestinal mucosa. Esophageal adverse disorders such as esophagitis, esophageal ulcers & erosions, occasionally with bleeding & rarely followed by esophageal stricture or perforation, have been reported in patients receiving Alendronate. Physicians should therefore be cautious to any signs or symptoms of a possible esophageal reaction & patients should be instructed to discontinue treatment with Alendronate & seek medical attention if they develop dysphasia, odynophagia, retrosternal pain or new or worsening heart burn.

The risk of severe esophageal adverse events appears to be greater in patients who lie down after taking the dose and/or who fail to swallow it with a full glass of water, and/or who continue to take Alendronate after developing symptoms indicative of esophageal irritation. In patients who cannot comply with dosing instructions due to mental disability, therapy with Alendronate should be used under appropriate supervision.

DRUG INTERACTIONS:

IV Ranitidine was shown to double the bioavailability of oral Alendronate. The clinical significance of this increase and whether similar increase will occur with oral H2-antagonists is unknown. Products containing Calcium & other multivalent cations are likely to interfere with absorption of Alendronate.

DOSAGE & ADMINISTRATION:

BONEMED must be taken at least one half-hour before the first meal, beverage, or medication of the day with plain water only. Other beverages (including mineral water), food, and some medications are likely to reduce the absorption of BONEMED. Failing to do so will result in lesser effects of BONEMED by decreasing its absorption. To facilitate delivery to the stomach & thus reduce the potential for esophageal irritation, BONEMED should only be swallowed upon arising for the day with a full (6-8 oz) glass of water & patient should not lie down for at least 30 minutes and until after their first meal of the day. BONEMED should not be taken at bed time or before arising for the day. Failure to follow these instructions may result in increased risk of esophageal adverse events.

Dosage

For treatment of osteoporosis: The recommended dose is 10mg

Once daily OR one 70 mg tablet once weekly.

For patients receiving glucocorticoids: The recommended dose is 5mg once daily, except for postmenopausal women not receiving estrogen for which the recommended dose is 10mg once daily.

For patients suffering from Paget's disease: The recommended treatment regimen is 40mg once daily for 6 months.

STORAGE:

Protect from heat, sunlight & moisture.

Keep in a dry place at temperature below 30°C.

Keep all medicines out of reach of children.

PRESENTATION:

BONEMED 10mg is available in a blister pack of 10 tablets. BONEMED 70mg is available in a blister pack of 4 tablets.