Alendronat

General characteristics. Structure:

Active ingredient: 10 mg or 70 mg of alendronovy acid in 1 tablet.

The drug inhibiting a bone resorption.

Pharmacological properties:

Pharmacodynamics. Works as specific inhibitor of the bone resorption mediated by osteoclasts — lowers activity of osteoclasts, brakes a resorption of a bone tissue.

Recovers positive balance between a resorption and recovery of a bone. Increases the mineral density of bones, promotes formation of a bone tissue with normal histologic structure.

Pharmacokinetics. Absorption in a GIT — 25%. Absolute bioavailability for the pill (10 mg) taken for 2 h to food makes 0,78% for women and 0,59% — for men. Average value of absolute bioavailability at women at reception of an alendronat in doses of 5-40 mg inside on an empty stomach for 2 h till a standard breakfast — 0,6%. In a research at 49 women in a postmenopause it was shown that at reception of 10 mg of an alendronat bioavailability decreases approximately by 40% if HP took for 0,5–1 h till a breakfast (in comparison with values of bioavailability for 2 h to food). At reception of an alendronat together with food or during 2 h after food bioavailability is insignificant. The concomitant use of an alendronat with coffee or with orange juice brings with decrease in bioavailability approximately for 60%.

Later in/in introductions in a dose of 1 mg/kg алендронат it is distributed in soft tissues, then quickly redistributed in a bone tissue or removed with urine (it is shown in preclinical tests on males of rats). The person has a distribution volume in an equilibrium state — 28 l. Concentration after intake in a therapeutic dose was in plasma below a measurement limit (1/2 terminal make more than 10 years.

Indications to use:

Pedzhet's disease (the deforming osteosis), osteoporosis at women in a postmenopause (prevention of fractures of bones, including a hip and backbone), osteoporosis at men, a hypercalcemia at malignant tumors.

Route of administration and doses:

Inside, without chewing, for 2 h (not less than 30 min.) before the first meal, washing down only with water.

The recommended dose at osteoporosis at women — 10 mg/days, for prevention — 5 mg/days.

At Pedzhet's disease — 40 mg/days within 6 months.

Features of use:

Use at pregnancy and feeding by a breast. Category of action on a fruit on FDA — C.

Tablets should be washed down only with usual water since other drinks (including mineral water, coffee, tea, orange juice) reduce absorption. For reduction of irritant action by upper parts of a GIT the tablet needs to be accepted right after morning rise, washing down with a full glass of water. It is not necessary to take a pill before going to bed. Within 30 min. after reception it is not recommended to hold horizontal position (reception before going to bed or in horizontal position increases risk of development of an esophagitis).

In the presence of a hypocalcemia it is necessary to correct it prior to therapy. The diet enriched with calcium is obligatory.

Side effects:

Treatment of osteoporosis at women in a postmenopause. By results of two three-year placebos - controlled double blind people of identical multicenter researches on design at treatment of osteoporosis at women in a postmenopause therapy was stopped in connection with development of side effects in the patients accepting алендронат in a dose of 10 mg/days in 4,1% (n=196) of cases and in 6,0% (n=397) of cases at the patients accepting placebo (the number of patients in a research — 994); according to other research (n=6459) therapy was stopped in connection with development of clinically expressed adverse effects in 9,1% of cases at the patients accepting алендронат in a dose of 5 mg/days within 2 years and 10 mg/days within 1 more year or 2 years and at 10% of patients from group of placebo.

Side effects which in these tests were considered by researchers as possibly or definitely connected with reception of an alendronat and met frequency of 1% (near the name the frequency of occurrence of this side effect, in brackets — similar data in group of placebo is specified): abdominal pain of 6,6% (4,8%), dyspepsia of 3,6% (3,5%), lock or diarrhea of 3,1% (1,8%), abdominal distention of 1,0% (0,8%), meteorism of 2,6% (0,5%), dysphagy of 1,0% (0,0%), esophagitis, ulcer or erosion of a gullet of 1,5% (0,0%); an ostealgia, muscles, joints of 4,1% (2,5%), a headache of 2,6% (1,5%), it is rare — rash, an erythema.

Other researches. Combined use of an alendronat about estrogen / гормонозамещающей therapy.

In two researches (lasting 1 and 2 years) at women with osteoporosis in a postmenopause (total number of the examinees, n=853) accepting on 10 mg of an alendronat of 1 times a day in a combination with эстрогеном±прогестином (n=354) safety and portability of an alendronat did not differ from similar indicators at separate carrying out the first and second types of treatment.

Treatment of osteoporosis at men. In two placebos - controlled double blind multicenter researches at men (a biennial research of an alendronat in a dose of 10 mg/days and a one-year research with reception of an alendronat in a dose of 70 mg once a week) therapy was stopped in connection with development of clinically expressed side effects in 2,7% of cases (n=146) and in 10,5% (n=95) against the background of placebo and in 6,4% of cases at the patients accepting алендронат in a dose of 70 mg once a week and at 8,6% of patients of group of placebo.

Side effects which were considered as it is probable, perhaps or definitely connected with reception of an alendronat and met the frequency of 2% (near the name the frequency of occurrence of this side effect, in brackets — similar data in group of placebo is specified): eructation of 4,1% (3,2%), meteorism of 4,1% (1,1%), gatroezofagealny reflux of 4,1% (3,2%), dyspepsia of 3,4% (0,0%), diarrhea of 1,4% (1,1%), abdominal pain of 2,1% (1,1%), nausea of 2,1% (0,0%).

Post-market researches. Organism in general: hypersensitivity reactions, including a small tortoiseshell and exceptional cases of a Quincke's disease; tranzitorny symptoms of a mialgiya, an indisposition, an adynamy and, seldom, fever cases, usually in an initiation of treatment; seldom — peripheral hypostases.

From bodies of a GIT: esophagitis, erosion and ulcers of a gullet; seldom — a stenosis or perforation of a gullet, a stomatopharynx ulcer, stomach ulcer or a duodenum; it was seldom reported about cases of the localized osteonecrosis of a jaw which is usually connected with extraction of tooth and/or a local infection it is frequent with a healing delay.

From a musculoskeletal system: the ostealgia, joints and/or muscles sometimes expressed and, seldom, resulting in disability.

From a nervous system and sense bodys: dizziness, вертиго; seldom — a uveitis, a sclerite or an episcleritis.

From integuments: rash (sometimes with photosensitivity), an itch; seldom — the expressed skin reactions, including Stephens-Johnson's syndrome and a toxic epidermal necrolysis.

Interaction with other medicines:

Drugs, calciferous, including antacids, reduce absorption. The interval between reception of an alendronat and other HP has to make not less than 1 h.

Ranitidine increases bioavailability twice (clinical value is not defined).

NPVS strengthen a gastrotoksichnost of alendronovy acid.

Contraindications:

Hypersensitivity, pregnancy, the lactation period, children's age (safety and efficiency of use are not defined).

Restrictions to use. Gastrointestinal diseases in an aggravation phase (a dysphagy, an esophagitis, gastritis, a duodenitis, a peptic ulcer of a stomach and duodenum), a stricture or an achalasia of a gullet, a chronic renal failure (at creatinine Cl).

Overdose:

Symptoms: hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis, gastritis, GIT erosive cankers.

Treatment: appointment in milk or kaltsiysoderzhashchy antacids for binding of an alendronat (because of risk of development of irritation of a gullet it is not necessary to cause vomiting), symptomatic therapy.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 10 mg, 20 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.

Tablets on 70 mg, 10 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.