Treatment of osteoporosis, postmenopausal.

Alendronate reduces the risk of vertebral and hip fractures

Alendronate should be taken, on an empty stomach with a large glass of tap water, immediately upon rising half an hour before the first intake of food, drink or other medicines. Other drinks (including mineral waters containing bicarbonate), foods and other medicines may decrease absorption, alendronate (see Interactions with other medicines and other forms of interactions).

In order to promote absorption at the gastric level and to reduce the risk of local adverse reactions and oesophageal irritation (see section 4.4), the following measures should be observed: Code>
· Alendronate should be taken only at morning rising with a large glass of tap water

· Alendronate tablets should be swallowed without chewing. The tablets should not be chewed or sucked because of the risk of oro-esophageal ulceration

Patients should not lie down (they should remain standing or sitting) until the first meal of the day is taken which will take at least half an hour, after taking the tablet. Br>

· Alendronate should not be taken at bedtime or before morning break.

Calcium and vitamin D supplementation is recommended in cases of insufficient dietary intakes (see Warnings and Precautions).
The recommended dosage is 10 mg in a daily dose.


Due to insufficient experience in use, alendronate is not recommended in patients with severe renal insufficiency (creatinine clearance
After collecting the data collected over 3 years, analysis of the results in the two largest numbers of treated patients who received different doses of alendronate after menopause led to the following findings: A reduction of 48% in the number of patients who presented with one or more vertebral bills (3.2% on alendronate versus 6.2% on placebo). In patients with a vertebral fracture, the decrease in size was less in patients with alendronate (5.9 mm vs 23.3 mm). After grouping data from five 2-3-year studies, they found a 29% reduction in the number of non-vertebral fractures (9.0% alendronate versus 12.6% placebo ).

Treatment with alendronate for 3 years (5 mg / day in the first 2 years and 10 mg / day in the 3 rd year) in osteoporotic menopausal women (who had at least vertebral compression) To obtain a reduction in the incidence rate of fractures as follows: Percentages of patients with at least one new vertebral fracture (8.0% alendronate versus 15.0% placebo, Percentages of patients with at least two new vertebral fractures (0.5% vs 4.9%, 90% reduction), clinical fractures (painful) (13.7% vs. 18% , 3%, 28% reduction), hip fracture (1.1% vs 2.2%, 51% reduction), and wrist fracture (forearm) (2.2% vs 4.1 %, 48% reduction).

Histology, bone

Data from bone histology in 270 postmenopausal women with osteoporosis and treated with alendronate at 1-20 mg / day for 1-3 years showed normal mineralization and bone structure and Predictable slowing of bone remodeling by; report to placebo group.

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

· Diseases of the esophagus, such as stenosis or achalasia that delay oesophageal transit.

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

· Hypersensitivity to alendronate, to others, to biphosphonates, or to any of the excipients.

· Hypocalcaemia.

See section 4.4 Warnings and precautions for use.
Alendronate 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 underlying disease, caution should be exercised when alendronate is given in patients with progressive high gastrointestinal disease such as dysphagia, Oesophageal disease, gastritis, duodenitis, ulcer, or recent history (occurring during the previous year) of a major gastrointestinal disease such as ulcer, gastroduodenal, haemorrhage Gastrointestinal, active or surgical procedure on the upper part of the gastrointestinal tract other than a pyloroplasty (see section Contraindications)

Esophageal reactions (sometimes with severity requiring hospitalization), such as esophagitis, ulcerations, and oesophageal erosions, rarely followed by oesophageal stenosis, have been reported in patients Receiving alendronate. Therefore, practitioners should be particularly careful of any signs or symptoms suggestive of a possible esophageal reaction and the patient should be instructed to discontinue alendronate and see if she has any symptoms, Oesophageal irritation such as dysphagia, pain in swallowing, pain, retrosternal or the onset or aggravation of a heartburn

The risk of occurrence of severe oesophageal reactions appears to be higher in patients who do not take alendronate correctly and / or continue to take alendronate therapy after developing symptoms suggestive of oesophageal irritation. It is very important to provide all information concerning the administration of the treatment to the patient and to ensure that she assimilates them (see Posology and method of administration). Patients should be advised that non-compliance with these instructions may increase their risk of developing esophageal disorders.
For patients with Barrett's esophagus, prescribers should consider the potential benefits and risks of administering alendronate on a case-by-case basis.
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In spite of the absence of increased risk in large-scale clinical studies, rare cases (after placing on the market) of ulcers, gastric and duodenal have been observed, some of which have A causal relationship can not be totally excluded

Alendronate is not recommended in patients with renal insufficiency in which the glomerular filtration rate (DFG) is less than 35 ml / min (see Dosage and Mode of Administration)

Other sources of osteoporosis should be considered as estrogen deficiency and aging.

Any hypocalcaemia should be corrected prior to initiation of treatment with alendronate (see section 4.3 Contraindications). Other disorders affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) must also be adequately corrected. In patients with these conditions, monitoring of serum calcium and symptoms suggestive of hypocalcaemia should be implemented during treatment with alendronate.
Due to the favorable incidence of alendronate on the increase in bone mineral density, decreases in serum calcium and phosphatemia can be observed, these decreases are generally small and asymptomatic. However, there have been rare reports of symptomatic hypocalcemia, on some occasions, severe and often occurring in patients with predisposing conditions (eg, hypoparathyroidism, vitamin D deficiency, and calcium malabsorption)

In patients with corticosteroids, it is particularly important to ensure adequate intake of calcium and vitamin D.

Fatigue fractures (also known as insufficiency fractures) of the femoral diaphysis have been reported in patients treated long-term with alendronic acid (time to onset in the majority; Of cases ranged from 18 months to 10 years). Fractures occurred after minimal or no trauma and some patients have thigh pain, often associated with imaging characteristics of fatigue fractures weeks or months before fracture of the femur. Fractures were often bilateral, so the contralateral femur should be examined in patients treated with bisphosphonates who have undergone femoral diaphysis fracture. The poor scarring of these fractures has also been reported. Discontinuation of bisphosphonate treatment in patients with fatigue fracture is recommended pending patient assessment based on an individual risk-benefit assessment.
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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 receiving bisphosphonate therapy. 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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AFSSAPS alert of 05/12/2011

- The European Medicines Agency (EMA) has concluded that the occurrence of atypical fractures of the femur exists for patients treated with biphosphonate-containing drugs (alendronate, clodronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate, Zoledronate). This rare effect, identified since 2008 for alendronate is therefore a class effect. It occurs especially during prolonged treatments.
Concomitant use of alendronate with medicinal products containing calcium, antacids and other oral medicinal products should be avoided because of the risk of interference with the absorption of alendronate. Patients should therefore wait at least half an hour between taking alendronate and taking other medications orally. The resorption of biphosphonates decreases considerably in the case of concomitant feeding (see Dosage and Mode of Administration).

In postmenopausal osteoporosis studies, several patients received estrogens (vaginally, cutaneously or orally) during alendronate therapy, and no adverse effects associated with this combination were found. >

No other clinically significant interactions are foreseeable on the basis of data on protein binding, renal elimination and metabolism, other active substances (see section Properties, pharmacokinetics) and none; Was observed when alendronate was administered at 10 mg / day in clinical trials in postmenopausal women with osteoporosis
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Not applicable.

Oral overdosage may result in hypocalcaemia, hypophosphatemia and adverse effects in the upper gastrointestinal tract such as gastric disorders, heartburn, esophagitis, gastritis, or ulcer. No specific information is available on the management of an overdose with alendronate. In these situations, milk or antacids should be administered to fix alendronate. Due to the risk of esophageal irritation, vomiting should be avoided and the patient should remain in an upright position.
Pregnancy

Information on the use of alendronate in pregnant women is insufficient. Animal studies did not reveal any direct adverse effects on embryonic, fetal, or postnatal gestation or development, administered during gestation in rats, alendronate caused dystocia related to , Hypocalcaemia (see section Safety data, preclinical). Due to its indication, alendronate should not be used during pregnancy.
Breastfeeding

It is not known whether alendronate is excreted in human breast milk. As indicated, alendronate should not be used by women who are breast-feeding

In two, three-year studies with almost identical modalities in postmenopausal women (10 mg, alendronate: n = 196, placebo: n = 397), overall safety profiles Alendronate 10 mg / day and placebo were similar.

The undesirable effects presented by the investigators as being in possible or probable relation to the active ingredient or unquestionably related to it are presented below if they occurred in 1% of patients treated with 10 Mg / day of alendronate and at a higher frequency than in patients receiving placebo in three-year studies

Studies on three years

Alendronate

Placebo

10 mg / day

(N '= 397)

(N '= 196)

%

%

Gastrointestinal effects

Abdominal pain

6,6

4.8

Dyspepsia

3.6

3,5

Acid regurgitation

2.0

4.3

Nausea

3.6

4.0

Abdominal bloating

1.0

0.8

Constipation

3.1

1.8

Diarrhea

3.1

1.8

Dysphagia

1.0

0.0

Flatulences

2.6

0.5

Gastritis

0.5

1.3

Gastric ulcer

0.0

0.0

Oesophageal ulceration

1.5

0.0

Musculoskeletal effects

Musculoskeletal pain (bone, muscle or joint pain)

4.1

2.5

Muscle cramps

0.0

1.0

Neurological effects

Headache

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,