Treatment of postmenopausal osteoporosis

Alendronate reduces the risk of vertebral and hip fractures

Orally only

The recommended dosage is 70 mg once a week.
To allow adequate absorption of alendronate

ACID ALENDRONIQUE ARROW 70 mg tablet should be taken on an empty stomach, immediately after morning rising, with a large glass of tap water only, at least half an hour before the first intake of food, drink or anything Other
Other drinks (including mineral water), foods and medications may decrease the absorption of alendronate (see section Interaction with other medicinal products and other forms of interaction).

To facilitate passage through the stomach and thus reduce the risk of irritation or local and esophageal adverse effects (see section 4.4) Br>

ACID ALENDRONIQUE ARROW 70 mg tablet should be taken strictly on rising with a large glass of tap water (minimum 200 ml).
ALENDRONIC ACID ARROW 70 mg; tablet should be swallowed whole. Patients should not chew, suck the tablet or let it dissolve in their mouth because of the potential risk of oropharyngeal ulcerations

Patients should not lie down until absorption of the first foods of the day which should be taken at least thirty minutes after taking the tablet. Br>
Patients should not lie down for at least 30 minutes after taking the tablet.
ACID ALENDRONIQUE ARROW 70 mg tablet should not be taken at or before bedtime.
Treated patients should be supplemented with calcium and vitamin D and if their dietary intakes are insufficient (see section 4.4).

Use in elderly patients

Clinical studies did not reveal any differences related to age in the efficacy and safety profiles of alendronate. Therefore, no change in dosage is necessary in elderly patients.


Dose modification is not necessary in patients with glomerular filtration rate (dfg) greater than 35 ml / min. Due to a lack of experience, alendronate is not recommended for patients with renal insufficiency, characterized by a GFR of less than 35 ml / min.
< Br>

Use in patients with hepatic impairment

No change in dosage is necessary.

Use in children (under 18 years of age)

Alendronate was studied in a limited number of patients under 18 years of age, with osteogenesis imperfecta. The results are insufficient to support its use in children

ACID ALENDRONIQUE ARROW 70 mg tablet has not been studied on the treatment of osteoporosis induced by corticosteroids

White-to-white tablet, broken, oval, marked "AN 70" on one side and ARROW logo on the other.

Class: Pharmacotherapeutic: Bisphosphonate, for the treatment of bone diseases, ATC code: M05B A04

The alendronic acid active ingredient arrow 70 mg, tablet, alendronate monosodium trihydrate, is a bisphosphonate, which inhibits bone resorption of osteoclasts without direct effect on bone formation. Preclinical studies have shown a preferential localization of alendronate to the active sites of resorption. The activity of the osteoclasts is inhibited, but neither their recruitment nor their binding is affected. During treatment with alendronate, the quality of the bone formed is normal.

Treatment of osteoporosis, postmenopausal

Osteoporosis is defined as a bone mineral density (BMD) at the spine or neck of the femur at 2.5 standard deviations below the mean value of a normal young population or by a previous fracture of Fragility, bone, independently of BMD.

The therapeutic equivalence of alendronate in weekly tablets (n '= 519) and alendronate 10 mg / day (n = 370) was demonstrated in a multicenter study of a duration 1-year postmenopausal women with osteoporosis. The mean increases in BMD at the level of the spine after 1 year, compared to the initial values, were 5.1% (95% CI: 4.8% -5.4%) in the group receiving 70 Mg once weekly and 5.4% (CI 95%: 5.0% -5.8%) in the 10 mg daily group. The mean increases in BMD in the group treated with 70 mg once a week and in the 10 mg mg once daily group were 2.3% and 2.9%, respectively, Of the femoral neck and 2.9% and 3.1% at the hip (femoral and trochanter). The two treatment groups were also similar, as for the increase in BMD at other sites in the skeleton.

The effects of alendronate on BMD and incidence of fractures in postmenopausal women were analyzed in two initial efficacy studies using identical protocol (n '= 994) and The study: Fracture Intervention Trial (FIT, n '= 6459).
In the initial efficacy studies, alendronate at a dose of 10 mg daily for 3 years resulted in increases in BMD at the lumbar spine, femoral neck, and trochanter, respectively 8.8%, 5.9%, and 7.8%, compared to placebo.
Entire body BMD also increased significantly. There was a 48% reduction in the rate of patients with one or more vertebral fractures in the group treated with alendronate versus the placebo group (alendronate 3.2% and placebo 6.2%). In the 2-year extension of these studies, BMD at the spine and trochanter levels continued to increase. In addition, femoral neck and whole body BMD were maintained.
The FIT trial included two studies, placebo-controlled with alendronate in daily use (5 mg daily for 2 years and 10 mg daily for one to two more years).

· FIT 1: a 3-year study in 2027 patients with at least one vertebral fracture. In this study, the daily administration of alendronate reduced the incidence of at least one new fracture, vertebral 47% (alendronate 7.9% versus placebo 15.0%). Statistically significant was observed on the incidence of hip fractures (1.1% versus 2.2%, a reduction of 51%).
· FIT 2: A 4-year study in 4432 patients with low bone mass but without vertebral fracture, pre-existing. In this study, in the analysis of the osteoporotic women subgroup (37% of the total population, which meets the definition of osteoporosis above), there was a significant difference in incidence Of hip fractures (alendronate 1.0% and placebo 2.2%, ie, a 56% reduction) and the incidence of at least one spinal fracture (2.9% and 5.8% , Or a reduction of 50%).

Alendronic Acid arrow 70 mg tablet has no effect on the ability to drive, vehicles or use machines

· Diseases of the esophagus and other factors that delay transit, esophageal stenosis and achalasia

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

Hypersensitivity to alendronate, to other bisphosphonates or to any of the excipients

· Hypocalcaemia.

See section Warnings and Precautions for Use.

Alendronate may cause local irritation of the mucosa at the upper digestive sphere. Due to the possibility of an aggravation of the underlying disease, caution should be exercised when alendronate is given to patients with a highly progressive gastrointestinal disorder, such as dysphagia, Oesophageal disease, gastritis, duodenitis or ulcer, or recent history (occurring during the previous year), major gastrointestinal disease such as gastric ulcer, gastrointestinal haemorrhage Active or surgical intervention on the upper part of the gastrointestinal tract other than a pyloroplasty (see section Contraindications)

Esophageal reactions (sometimes severe and requiring hospitalization), such as oesophagitis, ulcerations, and oesophageal erosions, rarely followed by stenosis of the esophagus, have been reported in patients treated with; The alendronate.

Therefore, practitioners should be particularly attentive to any signs or symptoms indicating a possible esophageal reaction. The patient should be instructed to stop alendronate and see if she has symptoms of oesophageal irritation such as dysphagia, odynophagia, retrosternal pain, or the onset or aggravation of Burns, retrosternal.
The risk of occurrence of severe esophageal adverse events appears to be higher in patients who do not take alendronate correctly and / or continue to take their alendronate treatment after having developed suggestive symptoms; An esophageal irritation. It is very important to provide all the information concerning the administration of the treatment to the patient and to ensure that she assimilates them (see Dosage and Mode of Administration). That the non-observance of these instructions is likely to increase their risk of presenting esophageal disorders.

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

Patients should be warned that if they forget to take their ACID tablet ARROW 70 mg tablet they should take it the next morning of the day they find out they should not take 2 tablets The same day, but they must resume their treatment normally once, per week to the day they had originally chosen.

Alendronate is not recommended for patients with renal insufficiency, characterized by a glomerular filtration rate (GFR) of less than 35 ml / min (see Posology and method of administration). Br>

Other origins should be considered: osteoporosis as estrogen deficiency, and aging

Hypocalcaemia should be corrected before beginning treatment with alendronate (see Contraindications).
Other disorders of bone metabolism (such as vitamin D deficiency and hypoparathyroidism) should also be adequately corrected before starting treatment with alendronate. In patients with these disorders, serum calcium and hypocalcaemia symptoms should be monitored during treatment with alendronate.

Due to the positive effects of alendronate on bone mineral density, decreases in serum calcium and phosphate levels may occur. These decreases are generally small and asymptomatic. However, rare cases of symptomatic hypocalcemia have been reported, sometimes severe and appearing, often in patients with predisposed areas (eg, hypoparathyroidism, vitamin D deficiency and calcium malabsorption)

It is therefore particularly important to ensure that patients taking corticosteroids have an adequate intake of calcium and vitamin D.

Due to the presence of lactose, this drug is contraindicated in cases of congenital galactosemia, glucose-galactose malabsorption syndrome or lactase deficiency.

Osteonecrosis of the jaw, usually associated with dental extraction and / or local infection (including osteomyelitis) has been reported, in cancer patients receiving treatment with bisphosphonates administered intravenously . Many of these patients also received chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients treated for osteoporosis receiving oral bisphosphonates.

Prior to bisphosphonate therapy in patients with concomitant risk factors (eg cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene), a dental check-up with appropriate dental care should be considered. >

During treatment, these patients should, if possible, avoid invasive dental procedures. Dental surgery can worsen the condition of patients developing osteonecrosis of the jaw during bisphosphonate treatment. For patients requiring dental procedures, there is no available data suggesting that discontinuation of bisphosphonate therapy reduces the risk of osteonecrosis of the jaw
< Br>

The clinical judgment of the treating physician should guide the conduct to be taken for each patient based on the assessment of the report, individual benefit / risk

Alert: AFSSAPS of 05/12/2011

- The European Medicines Agency (EMA) has concluded that the appearance of atypical fractures of the femur exists for patients treated with drugs containing a biphosphonate (alendronate, clodronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate , Zoledronate). This rare effect identified in 2008 for alendronate is therefore a class effect. It occurs especially during prolonged treatment.

- Atypical fractures are distinguished from fractures of the femur, "classical" by their localization and radiological characteristics. These short transverse or oblique fractures, often bilateral, may occur on any part of the femur between the lower part of the small trochanter and the supracondylar zone. They occur after minimal trauma or even without trauma.
In the event of concomitant administration, it is likely that foods and beverages (including mineral water), medicines containing calcium, antacids, as well as other oral medicines, interfere with With the absorption of alendronate.

Therefore, patients should wait at least half an hour between taking alendronate and taking other medicinal products orally (see Dosage and Mode of Administration). >

No other drug-mediated interaction is expected. In clinical studies, a number of patients received estrogens (vaginally, cutaneously, orally) while they were treated with alendronate. No adverse reactions associated with this association have been observed.

Although no specific interaction studies have been performed, alendronate has been concomitantly administered in clinical studies with a wide range of commonly used drugs with no obvious clinical adverse interaction. Br>

Without object.

Hypocalcaemia, hypophosphatemia and undesirable events in the upper part of the gastrointestinal tract such as poor digestion, heartburn, esophagitis, gastritis, or ulcer may occur in case of oral overdose.

No specific data on the management of alendronate overdosage are available. Milk or antacids should be administered to chelate alendronate. To avoid the risk of irritation, the esophagus should not induce vomiting and the patient should remain in a vertical position.
Use during pregnancy

Information on the use of alendronate in pregnant women is insufficient. Studies on the animal revealed effects on fetal ossification at high doses

Alendronate, administered during pregnancy in rats, resulted in hypocalcemic dystocia (see Preclinical Safety Data). Due to its indication, alendronate should not be used during pregnancy.
Use during 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 a one-year clinical study in postmenopausal women with osteoporosis, the overall safety profiles of alendronate 70 mg tablets in weekly intake (n = 519) and alendronate 10 Mg per day (n '= 370) were similar.
In two three-year clinical trials in postmenopausal women with a substantially identical protocol (alendronate 10 mg, n '= 196, placebo: n' = 397), the overall tolerance profiles of Alendronate 10 mg / day and placebo were similar.

Adverse reactions presented by the investigators as being in a possible or probable relationship to the drug or undeniably related to the drug 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

1 year study

3-year study

Alendronate 70 mg (n '= 519)%

Alendronate 10 mg / d (n '= 370)%

Alendronate 10 mg / d (n '= 196)%

Placebo (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

Abdominal bloating

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

Gastric ulcer

0.0

1.1

0.0

0.0

Oesophageal ulcer

0.0

0.0

1.5

0.0

Musculoskeletal diseases

Osteoarticular or muscular pain

2.9

3.2

4.1

2.5

Muscle cramps

0.2

1.1

0.0

1.0

Neurological

Headache

0.4

0.3

2.6

1.5

The following adverse reactions have been reported in the clinical and / or postmarketing studies of alendronate
Neurological Disorders

Frequent (≥ 1/100;