Alendronate

When ATH:
M05BA04

Characteristic.

Aminoʙifosfonat, synthetic analogue pyrophosphate, bound to hydroxyapatite, located in the bone. Alendronate sodium - a white crystalline non-hygroscopic powder, water-soluble, slightly soluble in alcohol, and practically insoluble in chloroform; molecular weight 325,12.

Pharmacological action.
Inhibiting bone resorption.

Application.

Paget's disease (deforming ostoz), osteoporosis in postmenopausal women (prevention of bone fractures, incl. hip and spine), osteoporosis in men, hypercalcemia malignant tumors.

Contraindications.

Hypersensitivity, pregnancy, lactation, childhood (Safety and efficacy have not been determined).

Restrictions apply.

Diseases of the digestive tract in the acute phase (dysphagia, esophagitis, gastritis, duodenitis, gastric ulcer and duodenal ulcer), stricture or achalasia of the esophagus, chronic renal failure (if Cl creatinine <35 ml / min increases the risk of cumulation), hypocalcemia, vitamin D deficiency.

Pregnancy and breast-feeding.

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Side effects.

Treatment of osteoporosis in postmenopausal women

After two three-year placebo-controlled, double-blind identical design multicenter studies in the treatment of osteoporosis in postmenopausal women discontinued therapy due to the development of side effects in patients, alendronate dose 10 mg / day 4,1% (n=196) cases and 6,0% (n=397) cases of patients, placebo (the number of patients in the study - 994); according to another study (n=6459) Therapy was discontinued due to the development of clinically significant adverse effects 9,1% cases of patients, alendronate dose 5 mg / day for 2 years 10 mg / day for another 1 year or 2 years and 10% patients in the placebo group.

Side effects, that these trials were considered by researchers as probably or definitely related to alendronate, and met with a frequency ≥1% (next to specify the frequency of occurrence of this side effect, in brackets - the same data in the placebo group): abdominal pain 6,6% (4,8%), dyspepsia 3,6% (3,5%), constipation or diarrhea 3,1% (1,8%), abdominal distention 1,0% (0,8%), flatulence 2,6% (0,5%), dysphagia 1,0% (0,0%), esophagitis, ulcer or erosion of the esophagus 1,5% (0,0%); bone pain, muscle, joints 4,1% (2,5%), headache 2,6% (1,5%), rarely - rash, эritema.

Other research. Combined use of alendronate with estrogen / hormone replacement therapy

In two studies (duration 1 and 2 year) in women with postmenopausal osteoporosis (the total number of subjects, n=853), Take on 10 mg alendronate 1 once a day in combination with estrogen ± progestin (n=354) safety and tolerability of alendronate did not differ from the respective figures in the separate holding of the first and second types of treatment.

Treatment of osteoporosis in men

In two placebo-controlled, double-blind, multicenter studies in men (year study at a dose of alendronate 10 mg / day and one-year study at a dose of alendronate 70 mg 1 once a week) Therapy was discontinued due to the development of clinically significant side effects 2,7% cases (n=146) and in 10,5% (n=95) on placebo and 6,4% cases of patients, alendronate dose 70 mg 1 once a week and 8,6% placebo patients.

Side effects, which were seen as likely, probably or definitely related to alendronate, and met with a frequency ≥2% (next to specify the frequency of occurrence of this side effect, in brackets - the same data in the placebo group): belching 4,1% (3,2%), flatulence 4,1% (1,1%), hatroэzofahealnыy reflux 4,1%(3,2%), dyspepsia 3,4% (0,0%), diarrhea 1,4% (1,1%), abdominal pain 2,1% (1,1%), nausea 2,1% (0,0%).

Post-marketing studies

Body as a Whole: hypersensitivity reactions, including urticaria, and rare cases of angioedema; Transient symptoms of myalgia, malaise, asthenia and, rarely, fever cases, usually at the beginning of treatment; rarely - peripheral edema.

From the digestive tract: esophagitis, erosion and ulceration of the esophagus; rarely - stenosis or perforation of the esophagus, ulceration of the oropharynx, a stomach ulcer or duodenal ulcer; rarely reported cases of localized osteonecrosis of the jaw, typically associated with tooth extraction and / or local infection, often with delayed healing.

On the part of the musculoskeletal system: bone pain, the joints and / or muscles, sometimes severe and, rarely, leading to disability.

From the nervous system and sensory organs: dizziness, vertigo; rarely - uveitis, scleritis or episcleritis.

For the skin: rash (occasionally with photosensitivity), itch; rare - marked skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Cooperation.

Preparations, containing calcium, incl. antacids, reduce the absorption. The interval between alendronate and other drugs should be at least 1 no. Ranitidine increases the bioavailability 2 times (the clinical significance is not defined). NSAIDs increase gastrotoxicity alendronate.

Overdose.

Symptoms: hypocalcemia, gipofosfatemiя, diarrhea, heartburn, esophagitis, gastritis, erosive and ulcerative lesions of the gastrointestinal tract.

Treatment: appointment into milk or calcium-containing antacids to bind alendronate (because of the risk of irritation of the esophagus should not induce vomiting), simptomaticheskaya therapy.

Dosing and Administration.

Inside, without chewing, for 2 no (no less 30 m) before the first meal, drinking water only. The recommended dose for osteoporosis in women - 10 mg / day, prevention - 5 mg / day. When Paget's disease - 40 mg / day for 6 Months.

Precautions.

The tablets should be taken with plain water only, tk. other drinks (incl. mineral water, coffee, tea, Orange juice) reduce the absorption. In order to reduce irritation to the upper gastrointestinal tablet should be taken immediately after the morning rise, with a full glass of water. Do not take the tablets before going to bed. During 30 minutes after administration is not recommended to take a horizontal position (Reception at bedtime or in the horizontal position increases the risk of esophagitis).

In the presence of hypocalcemia should be corrected prior to its treatment. Mandatory diet, calcium fortified.

Cooperation