Treatment of postmenopausal osteoporosis

Alendronic acid reduces the risk of vertebral and hip fractures

The recommended dosage is 1 tablet at 70 mg once a week.


Alendronic acid should be taken at least 30 minutes prior to absorption of the first foods, beverages or medications of the day with a large glass of tap water. Other drinks (including mineral water), foods or certain drugs may decrease the absorption of alendronic acid (see section Interactions with other medicines and other forms of interaction).

To facilitate passage through the stomach and thereby reduce the potential for irritation or local and esophageal adverse reactions (see section 4.4). >

Alendronic acid should be taken strictly at the rising, with a large glass of tap water (minimum 200 ml).

· The tablets should not be chewed or sugared due to the potential risk of oropharyngeal ulceration

· Patients should not lie down until the first meal of the day is taken which will occur at least 30 minutes after taking the tablet. >
· Patients should not lie down for at least 30 minutes after taking acid, alendronics

· Alendronic acid should not be taken at bedtime or before morning rising.

Calcium and vitamin D supplementation is recommended in the case of insufficient dietary intakes (see section 4.4 Warnings and Precautions).
Use in the elderly

Clinical studies did not reveal any differences related to age in the efficacy and tolerance profiles of alendronic acid. Therefore, no dosage adjustment is necessary in the elderly.


None, dosage adjustment is necessary in patients with glomerular filtration rate (GFR)> 35 ml / min. In the absence of experimental data, alendronic acid should not be administered to patients with renal insufficiency characterized by TFG
Use in children and adolescents (under 18 years of age)

Alendronic acid was studied in a small number of patients under 18 years of age with osteogenesis imperfecta. The results are not sufficient to recommend this treatment in children and adolescents

Round and flat tablet with beveled edges of white to whitish color, bearing on one side an engraved T, the other side being smooth.

Class: Pharmacotherapeutic: Bisphosphonate, for the treatment of bone diseases

ATC code: M05B A04.

The active ingredient is a bisphosphonate, which inhibits bone resorption of osteoclasts without direct effect on bone formation. Preclinical studies have shown a preferential localization of alendronic acid to sites of active resorption. The activity of the osteoclasts is inhibited, but neither their recruitment nor their attachment is affected. The bone formed during treatment with alendronic acid is of normal quality.

Treatment of osteoporosis, postmenopausal

Osteoporosis is defined as bone mineral density (BMD), with the spine or hip below 2.5 standard deviation below the mean value of a normal young population or a previous history of fracture , Fragility, regardless of BMD.

The therapeutic equivalence of alendronic acid 70 mg (n '= 519) and alendronic acid 10 mg / day (n = 370) was demonstrated in a one-year multicentre Postmenopausal women with osteoporosis. At one year, the mean increases in BMD at the lumbar spine from baseline were 5.1% (95% CI 4.8% -5.4%) in the 70 mg group Times per week and 5.4% (95% CI, 5.0% -5.8%) in the 10 mg daily group. The mean BMD increases were 2.3% and 2.9% for the femoral neck and 2.9% and 3.1% for the total hip in the 70 mg groups, respectively. Week and 10 mg daily. Increases in BMD at other sites in the skeleton were also similar in both groups

The effects of alendronic acid on bone mass and the incidence of fractures in postmenopausal women were analyzed in two initial efficacy studies using the same methodology (n = 994) and In the FIT (Fracture Intervention Trial) study (n '= 6,459).
In the initial efficacy studies, mean increases in BMD were 8.8%, 5.9%, and 7.8%, respectively, in the spine, femoral neck and trochanter with acid; Alendronic 10 mg daily for 3 years compared to placebo. There was also a significant increase in whole body BMD. There was a 48% reduction in the number of patients with one or more vertebral fractures in the group treated with alendronic acid compared to placebo (alendronic acid 3.2% versus placebo 6.2%) . In the two-year extension of these studies, the increase in BMD at the spine and trochanter continued and BMD of the femoral neck and whole body remained stable
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The FIT trial consisted of two, placebo-controlled studies of alendronic acid in daily administration (5 mg daily for two years and 10 mg daily for one to two years, additional)

· FIT 1: A 2-year study of 2,027 patients with at least one vertebral fracture (settlement) at the beginning of the study. In this study, the daily administration of alendronic acid reduced the incidence of at least one new vertebral fracture by 47% (alendronic acid 7.9% versus placebo 15%). There was also a statistically significant reduction in the incidence of hip fractures (1.1% versus 2.2%, a reduction of 51%).
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· FIT 2: 4-year study of 4,432 patients with low bone mass but without pre-existing vertebral fracture. In this study, the analysis of the subgroup of osteoporotic women (37% of the overall population corresponding to the above definition of osteoporosis) showed a significant difference in the incidence of fractures of; (Alendronic acid 1.0% versus placebo 2.2%, ie, a 56% reduction) and the incidence of at least one vertebral fracture (2.9% versus 5.8%, a reduction Of 50%).

Alendronic acid has no or negligible effect on the ability to drive or use machines

· Abnormalities of the esophagus and other factors that may delay oesophageal transit such as stenosis or achalasia

· Inability to stand or sit for at least 30 minutes.

· Hypersensitivity to acid, alendronic or to any of the excipients.
· Hypocalcaemia.

See also Warnings and precautions for use.

Alendronic acid may cause local irritation of the mucosa at the level of the upper digestive sphere. To the extent that there is a risk of aggravation of the disease underlying, caution is warranted when alendronic acid is given in patients with a high-progressive gastrointestinal disease such as; Dysphagia, oesophageal disease, gastritis, duodenitis, ulcer, or recent history (occurring during the preceding year) of major gastrointestinal disease such as ulcer, gastroduodenal, Active gastrointestinal haemorrhage or surgery on the upper part of the gastrointestinal tract other than a pyloroplasty (see section Contraindications.)

Esophageal reactions (occasionally severe, requiring hospitalization) such as oesophagitis, ulcerations, and esophageal erosions, rarely followed by stenosis of the esophagus, have been reported in patients receiving Of alendronic acid. Therefore, practitioners should be particularly attentive to any signs or symptoms suggestive of a possible esophageal reaction, and the patient should be instructed to stop alendronic acid and see if it has symptoms, Oesophageal irritation such as dysphagia, pain in swallowing, pain, retrosternal or the onset or aggravation of heartburn

The risk of occurrence of severe esophageal adverse effects appears to be higher in patients who do not take alendronic acid properly and / or continue to take alendronic acid after developing symptoms suggestive of oesophageal reflux, Oesophageal irritation. It is very important to provide the patient with all information concerning the administration of the treatment to the patient and to ensure that they have been understood (see Dosage and Mode of Administration.)

Patients should be advised that non-compliance with these instructions may increase their risk of developing esophageal disorders.

In spite of the absence of increased risk in large-scale clinical studies, rare (post-marketing) cases of gastric and duodenal ulcerations have been observed, some of which have Character of gravity, accompanied by complications. A relation of cause to effect can not be totally excluded.

Patients should be warned that if a dose of alendronic acid is forgotten, they should take one tablet the next morning when they realize it. They should not take two tablets on the same day, but return to the weekly intake of the tablet based on the day chosen initially.
Alendronic acid is not recommended in patients with renal insufficiency characterized by glomerular filtration rate (GFR) of less than 35 ml / min (see Dosage and Mode of Administration.) < Code>
Other origins should be considered: osteoporosis as estrogen deficiency, and aging

Hypocalcaemia should be corrected before treatment with alendronic acid (see Contraindications section). Also, other disorders of bone metabolism (such as deficiencies of vitamin D and hypoparathyroidism) must also be effectively corrected. In patients with these disorders, calcium and symptoms of hypocalcaemia should be monitored during treatment with alendronic acid.

Due to the positive effects of alendronic acid on bone mineralization a decrease in serum calcium and phosphate may occur and is usually low and asymptomatic. However, rare cases of symptomatic hypocalcemia, sometimes severe and often occurring in patients with predisposed conditions (eg, hypoparathyroidism, vitamin D deficiency, and calcium malabsorption) have been reported. Br>

Adequate intake of calcium and vitamin D is therefore particularly important in patients receiving corticosteroids.

Osteonecrosis of the jaw, generally associated with tooth extraction and / or local infection (including osteomyelitis) has been reported in patients receiving cancer, including treatments Bisphosphonates mainly via the intravenous route. A large number of these patients also received chemotherapy and corticosteroids.Jaw osteonecrosis has also been reported in patients with osteoporosis and oral bisphosphonates
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Dental examination and preventive measures should be considered prior to bisphosphonate therapy in patients with concomitant risk factors (including cancer, chemotherapy, radiotherapy, corticosteroids, Poor oral hygiene).

If possible, these patients should avoid invasive dental procedures during treatment. Dental surgery may exacerbate osteonecrosis of the jaw developed in patients treated with bisphosphonates. For patients requiring dental procedures, no data are available, suggesting that discontinuation of bisphosphonate therapy reduces the risk of osteonecrosis of the jaw

The physician will rely on his / her clinical judgment to guide the management of each patient according to the individual assessment of the report, risk / benefit.
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In the case of concomitant use, it is likely that foods and beverages (including mineral water), medicinal products containing calcium, antacids, and other medicines administered orally interfere with; The absorption of alendronic acid. Therefore, patients should wait at least 30 minutes after taking alendronic acid before taking any other oral medicinal products (see sections 4.2 and 4.2). >

No other drug-mediated interaction is expected. In clinical studies, a number of patients received estrogens (vaginal, cutaneous, or oral) while treated with alendronic acid. No undesirable effects related to this association have been observed.

Although no specific interaction studies have been performed, alendronic acid has been concomitantly administered in clinical studies with a wide range of drugs commonly used without clinical adverse interaction. >

Not applicable.

An oral overdose may lead to hypocalcaemia, hypophosphatemia and undesirable events in the upper gastrointestinal tract, such as nausea, burns, stomach, esophagitis, gastritis or ulcer. Br>

No specific information is available on the action to be taken in case of overdosage with alendronic acid. Milk or antacids should be administered to chelate alendronic acid. Due to the risk of esophageal irritation, vomiting should be avoided and the patient should remain in an upright position.
Use during the pregnancy

There are no adequate data on the administration of alendronic acid in pregnant women. Animal studies do not indicate direct adverse effects on gestation or embryo / fetal development or postnatal development. When administered during gestation in rats, alendronic acid caused a related dystocia, hypocalcaemia (see section Preclinical safety data). Due to its indication, alendronic acid should not be used during pregnancy.


There is no data on the passage of alendronic acid into breast milk. Due to its indication, alendronic acid should not be used in breast-feeding women.

In a 1-year clinical study in postmenopausal women with osteoporosis, the overall safety profiles of alendronic acid 70 mg (n = 519) and alendronic acid 10 mg / Day (n '= 370) were similar.
In two clinical trials of a 3-year duration in postmenopausal women (alendronic acid 10 mg: n = 196, placebo: n = 397) with a substantially identical protocol, the overall tolerance profiles of Alendronic acid 10 mg / day and placebo were similar.


Study over 1 year; (%)

Study over 3 years; (%)

Acid, alendronic

Acid, alendronic

Acid, alendronic

Placebo

70 mg

10 mg / day

10 mg / day

(N '=; 519)

(N '= 370)

(N '= 196)

(N '= 397)

Gastrointestinal

Abdominal pain

3.7

3.0

6,6

4.8

Dyspepsia

2.7

2.2

3.6

3,5

Acid regurgitation

1.9

2.4

2.0

4.3

Nausea

1.9

2.4

3.6

4.0

Bloating, abdominal

1.0

1,4

1.0

0.8

Constipation

0.8

1.6

3.1

1.8

Diarrhea

0.6

0.5

3.1

1.8

Dysphagia

0.4

0.5

1.0

0.0

Flatulence

0.4

1.6

2.6

0.5

Gastritis

0.2

1.1

0.5

1.3

Ulcer, gastric

0.0

1.1

0.0

0.0

Ulcer, oesophageal

0.0

0.0

1.5

0.0

Musculoskeletal diseases

Pains, osteoarticular or muscular

2.9

3.2

4.1

2.5

Cramps, muscle

0.2

1.1

0.0

1.0

Neurological

Headache

0.4

0.3

2.6

1.5

The following adverse events have been reported in clinical studies and / or after the marketing of alendronate
Frequent (> 1/100, 1/1000; 1 / 10,000,