COMPOSITION:

Active substance:

Alendronic acid;

1 tablet contains Sodium Alendronate, equivalent to Alendronic acid 10 mg or 70 mg.

Additional ingredients: Microcrystalline cellulose, Lactose monohydrate, Croscarmellose

sodium, Magnesium stearate, Colloidal anhydrous silica.

INDICATIONS:

– Treatment and prophylaxis of osteoporosis in postmenopausal women for the prevention

of fractures, including those of hip and spine (vertebral compression fractures).

– Treatment of osteoporosis in men for the prevention of fractures.

– Treatment and prophylaxis of glucocorticoid-induced osteoporosis;

DOSAGE:

The medicine should be taken immediately on getting up, swallowing the tablet as

whole and without chewing or dissolving, with full glass of water only for at least

30 min before your first meal, water or other drugs of a day. Other beverages, food

or drugs can decrease the absorption of alendronate. One should never lie down for

at least 30 min and until after your first food of a day to decrease an irritant

action on oesophagus. Do not take the drug before going to bed or before getting

up or lying down in horizontal position after taking the drug. Failure to follow

this instruction may increase the risk of oesophageal side effects.

In addition to the drug treatment it is recommended to change a way of life for

patients with osteoporosis – to stop smoking, to limit taking alcohol, to do exercises,

to stick to calcium diet.

The recommended dose for osteoporosis treatment in postmenopausal women and menn

is 1 tablet (10 mg) per a day or 1 tablet (70 mg) per a week. It is also prescribed

with calcium supplements in dose 0.5 g of calcium per a day. The treatment lasts

for a long time – for years. The recommended dose for osteoporosis prophylaxis in

postmenopausal women is 5 mg per a day. For the treatment and prophylaxis of glucocorticoid-induced

osteoporosis in men and women the recommended dosage is 5 mg once per a day, except

for postmenopausal women not receiving estrogens, for which the recommended dosage

is 10 mg once per a day. Appropriate pharmaceutical form and dosage of the preparation

should be used during administration of the dosage of 5 mg.

ADVERSE REACTIONS:

The following gastrointestinal adverse reactions can appear:

Heartburn, nausea, vomiting, acid eructation, epigastric pain, dyspepsia, dysphagia,

meteorism, abdominal swelling, constipation, diarrhoea, melena; rarely- oesophagitis,

oesophageal erosions and oesophageal ulcers; in isolated cases stenosis and oesophagus

perforation, oropharynx ulcers, gastric ulcer and duodenal ulcer were observed.

In single cases the following allergic reactions may occur:

Skin rash, hyperaemia,

itch, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria and in isolated

cases – angioneurotic edema.

In some patients who took the preparation there were noted asymptomatic hypocalcemia

and hypophosphatemia, headache, myalgia, sometimes – uveitis, scleritis or episcleritis.

Drug interactions:

The absorption of Alendronate is decreased in case of concomitant usage with calcium

supplement (including food supplements) and antacids. An interval between the preparation

intake and other per oral drugs usage must be not less than 1 hour.

Combined usage of Sodium Alendronate and hormone replacement therapy (estrogens

+ progesterones) caused more bone weight increase and more significant bone rosorption

decrease in comparison with the individual usage of the first and second treatment

metods.

NSAIDs increase gastrointestinal action of Sodium Alendronate.

Increase of hypocalcaemia is possible during simultaneous Sodium Alendronate usage

with glucocorticoids can because they suppress the vitamin D activity that results

in decrease of absorption of calcium and its more active excretion.

It is recommended to be on guard in case of usage of Alendronate with aminoglycosides,

which decrease calcium level in serum for a long time. The usage of thiazides, which

decrease the calcium elimination with urine, can interfere with the calcium decreasing

effect of Alendronate in the treatment of malignant hypercalcemia treatment.

Pregnancy and lactation:

It is contraindicated.

Children:

Contraindicated to children under 18 years old.

PRECAUTIONS:

⇒ Take the medicine as soon as you get up for the day 30 min before your first

meal in sitting or standing position only.

⇒ Drink full glass of plain water after Alendra® tablet because any other beverage

will decrease absorption of this drug (Do not use mineral water).

⇒ Do not chew or dissolve the tablets because of risk of oropharynx ulceration.

⇒ Do not lie down for at least 30 min after taking the medicine (do not take

this drug if you are not in sitting or upright standing position for 30 min). Taking

medicine in lying position or at bedtime increases the risk of oesophagus development

(mucous coat esophagitis).

⇒ Interval between taking Sodium Alendronate and other medicine taken per oral

should not be less than 1 hour.

⇒ The drug should be carefully used in patients with acute upper gastrointestinal

diseases (dysphagia, oesophagus diseases, gastritis, duodenitis, and ulcers) because

of possible irritant action of Alendra® on mucus.

⇒ Treatment by the preparation should be combined with calcium-fortified diet.

Patients should receive additionally about 0.5 g of calcium per a day, except in

the cases of hypercalcemia (malignant or medicament) treatment.

⇒ The calcium supplements and the products contained calcium should not be

taken for 1 – 2 hours after intake of Alendronate, because calcium delays Alendronate

(and other bisphosphonates) absorption from intestine.

⇒ In case of once a week dosage schedule, choose the day of week which best

fits your schedule. Every week, take one tablets on the same day of week which you

have chosen. ⇒ If you miss a dose, take only one tablet in the next morning

after you remember. Do not take two tablets on the same day. Then use the drug as

usual – take next one tablet the day you have chosen according your schedule of

the treatment.

In case of appearance of oesophagus disease symptoms (such as complications or pain

upon swallowing, chest pain, new or worsening heartburn) you should stop the preparation

usage and make an additional examination).

Before the beginning of the therapy by Alendra® patients with hypocalcaemia and

other mineral metabolism disorders (such as vitamin D deficiency) should get appropriate

treatment because level of serum calcium and phosphates may decrease during the

Alendronate treatment.

The usage of Alendronate can be combined with supplemental vitamin D.

There is no need to correct the dosage for elderly patients and patients with renal

insufficiency from mild to moderate (creatinin clearance from 35 to 60 ml/min).

Ability to influence reaction velocity while driving or operating any other mechanisms.

There are no data concerning the influence of Alendra® on ability to drive car and other machines.

Overdose:

Symptoms:

Hypocalcaemia, hypophosphatemia, stomach upset, heartburn, oesophagitis, gastritis

or gastric ulcer.

Treatment. Milk or antacids should be given to bind alendronate. Due to risk of

oesophageal irritation, vomiting should not be induced and the patient should remain

fully upright.

Ability to influence reaction velocity while driving or operating

any other mechanisms.

There are no data concerning the influence of Alendra® on ability to drive car and

other machines.

CONTRAINDICATIONS:

Hypersensitivity to Sodium Alendronate or other

drug ingredient; inability to stand or sit upright for at least 30 min after drug

intake; hypocalcemia; oesophagus involvement, which delay oesophageal empting, such

as stricture or achalasia of oesophagus; severe renal insufficiency (creatinine

clearance < 35 ml/min); concomitant usage with other bisphosphonates; pregnancy

and lactation period; children under 18 years old.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics. Sodium Alendronate is one of the aminobisphosphonates group. It

is a synthetic analogue of nature pyrophosphate. It inhibits precipitation of calcium

phosphate, blocks its transformation into hydroxyapatite, delays the aggregation

of apatite crystals with formation of bigger crystals and accelerates resolution

of these crystals. Selective action is caused by high affinity of bisphosphonates

and mineral components of bone. It acts as effective non-hormonal specific inhibitor

of osteoclast mediated bone resorption. Accurate mechanisms of this process are

not still cleared up. It promotes positive balance of resorption and bone renovation.

It increases a mineral density of the spine, pelvic and other bones, promotes the

formation of bone tissue with normal histological structure. It prevents new bone

fractures. It decreases the calcium level in serum as a result of inhibition of

bone resorption and decrease of calcium release from bone tissue. The preparation

action of calcium decrease, mediated as a result of osteoclast inhibition, is observed

in1 – 2 days.

Pharmacocinetics. 25% of Sodium Alendronate is absorbed gastro intestinal tract.

Absolute bioavailability of tablets (from 5 to 10 mg) has taken an empty stomach

before 2 hours to a meal is 0.64% (for wpmen) and 0.59% (for men). Bioavailability

decreases (approximately on 40%) in Alendronate intake before half an hour – hour

before usual breakfast. Alendronate bioavailability is small while its usage with

a meal or during two hours after a meal. Simultaneous usage of Alendronate with

other beverages (including mineral water, coffee, Orange juice) decreases its bioaviability

to 60%. Trials conducted on laboratory rats show that in intravenous introduction

of the drug in dosage 1 mg/kg Alendronate is temporarily distributed in soft tissues

and then quickly is redistributed.

Very small amount <1% of ingested from, therefore, it is very important to follow

the instruction regarding how to take the tablets. The half of absorbed dose is

mainly eliminated unchanged through kidneys over 72 hours, and the rest is sequestered

in bone tissues for a long time and is eliminated extremely slowly as a result of

strong bonding with bone tissue. Half-excretion period of Alendronate from bones

is several years.

Approximately 78% of Alendronate binds with plasma proteins and is not metabolized.

The preparation concentration in plasma is small (less than 5 ng/ml) and is decreasing

to 95% during 6 hours after intravenous infusion. After single oral introduction

of 10 mg of Alendronate its renal clearance was 71 ml/min and systemic clearance

did not exceed 200 ml/min.

PHARMACEUTICAL CHARACTERISTICS:

General physico-chemical properties:

round, biconvex, white or nearly white tablets

(10 mg) or oval, biconvex, white or nearly white tablets (70 mg).

Shelf-life:

3 years.

Storage:

Keep it out of reach of children, in dry place at a temperature vot more 25°C.

Package:

Tablets (10 mg). There are 10 tablets in blister, there are 3 blisters in a carton

box № 30 (10×3). Tablets 70 mg. There are 4 tablets in blister, each blister is

in a carton envelop № 4.

Conditions of supply:

By prescription.