Alendronic Acid 70mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Alendronic Acid 70 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains the equivalent of 70 mg of alendronic acid as 91.37 mg alendronate monosodium trihydrate.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Tablet.
White oval biconvex tablets, with dimensions of 14 x 8 mm and marked on one face with “70”
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of postmenopausal osteoporosis. Sodium alendronate reduces the risk of vertebral and hip fractures.
4.2. Posology and method of administration
The recommended dosage is one 70 mg tablet once weekly.
To permit adequate absorption of alendronate:
Sodium alendronate must be taken at least 30 minutes before the first food, beverage, or medicinal product of the day with plain water only. Other beverages (including mineral water), food and some medicinal products are likely to reduce the absorption of alendronate (see 4.5 'Interaction with other medicinal products and other forms of interaction').
To facilitate delivery to the stomach and thus reduce the potential for local and oesophageal irritation/adverse experiences (see 4.4 'Special warnings and precautions for use'):
• Sodium alendronate should only be swallowed upon arising for the day with a full glass of water (not less than 200 ml or 7 fl.oz.).
• Patients should not chew the tablet or allow the tablet to dissolve in their mouths because of a potential for oropharyngeal ulceration.
• Patients should not lie down until after their first food of the day which should be at least 30 minutes after taking the tablet.
• Patients should not lie down for at least 30 minutes after taking Sodium alendronate.
• Sodium alendronate should not be taken at bedtime or before arising for the day.
Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see 4.4 'Special warnings and precautions for use').
Use in the elderly: In clinical studies there was no age-related difference in the efficacy or safety profiles of alendronate. Therefore no dosage adjustment is necessary for the elderly.
Use in renal impairment: No dosage adjustment is necessary for patients with GFR greater than 35 ml/min. Alendronate is not recommended for patients with renal impairment where GFR is less than 35 ml/min, due to lack of experience.
Paediatric patients: Alendronate sodium is not recommended for use in children under the age of 18 years due to insufficient data on safety and efficacy in conditions associated with paediatric osteoporosis (also see section 5.1).
Sodium alendronate 70 mg Tablets has not been investigated in the treatment of glucocorticoid-induced osteoporosis.
4.3 Contraindications
Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Hypersensitivity to alendronate or to any of the excipients.
• Hypocalcaemia.
• See also 4.4 'Special warnings and precautions for use'.
4.4 Special warnings and precautions for use
While no increased risk was observed in extensive clinical trials, there have been rare (post-marketing) reports of gastric and duodenal ulcers, some severe and with complications. A causal relationship cannot be ruled out.
In patients with known Barett’s Oesophagus, prescribers should consider the benefits and potential risks of alendronic acid on an individual patient basis.
“Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis), has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.
During biphosphonate treatment, all patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain or swelling.”
Atypical fractures of the femur
Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique, fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.
4.5 Interaction with other medicinal products and other forms of interaction
If taken at the same time, it is likely that food and beverages (including mineral water), calcium supplements, antacids, and some oral medicinal products will interfere with absorption of alendronate. Therefore, patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product (see 4.2 'Posology and method of administration' and 5.2 'Pharmacokinetic properties').
No other interactions with medicinal products of clinical significance are anticipated. A number of patients in the clinical trials received oestrogen (intravaginal, transdermal, or oral) while taking alendronate. No adverse experiences attributable to their concomitant use were identified.
Although specific interaction studies were not performed, in clinical studies alendronate was used concomitantly with a wide range of commonly prescribed medicinal products without evidence of clinical adverse interactions.
4.6 Pregnancy and lactation
There are no adequate data from the use of alendronate monosodium trihydrate in pregnant women. Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, or postnatal development. Alendronate given during pregnancy in rats caused dystocia related to hypocalcemia (see 5.3 'Preclinical safety data'). Given the indication, alendronate should not be used during pregnancy.
It is not known whether alendronate is excreted into human breast milk. Given the indication, alendronate should not be used by breast-feeding women.
4.7 Effects on ability to drive and use machines
No effects on ability to drive and use machines have been observed.
4.8 Undesirable effects
In a one-year study in post-menopausal women with osteoporosis the overall safety profiles of 'Fosamax' Once Weekly 70 mg (n=519) and alendronate 10 mg/day (n=370) were similar.
In two three-year studies of virtually identical design, in post-menopausal women (alendronate 10 mg: n=196, placebo: n=397) the overall safety profiles of alendronate 10 mg/day and placebo were similar.
Adverse experiences reported by the investigators as possibly, probably or definitely dmg-related are presented below if they occurred in ^ 1% in either treatment group in the one-year study, or in ^ 1% of patients treated with alendronate 10 mg/day and at a greater incidence than in patients given placebo in the three-year studies:
|
One-Year Study |
Three-Year Studies | |||
|
'Fosamax' |
Alendronate |
Alendronate |
Placebo | |
|
Once Weekly |
10 mg/day |
10 mg/day | ||
|
70 mg |
(n = 397) | |||
|
(n = 370) |
(n = 196) | |||
|
(n = 519) | ||||
|
% |
% |
% |
% | |
|
Gastro-intestinal | ||||
|
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 distention |
1.0 |
1.4 |
1.0 |
0.8 |
|
constipation |
0.8 |
1.6 |
3.1 |
1.8 |
|
diarrhoea |
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 | ||||
|
musculoskeletal (bone, |
2.9 |
3.2 |
4.1 |
2.5 |
|
muscle or joint) pain | ||||
|
muscle cramp |
0.2 |
1.1 |
0.0 |
1.0 |
|
Neurological | ||||
|
headache |
0.4 |
0.3 2.6 |
1.5 | |
The following adverse experiences have also been reported during clinical studies and/or post-marketing use:
Common ( -1/100, < 1/10)
Gastro-intestinal: abdominal pain, dyspepsia, constipation, diarrhoea, flatulence, oesophageal ulcer*, dysphagia*, abdominal distension, acid regurgitation.
Musculoskeletal:
Common ( * 1/100, <1/10) musculoskeletal (bone, muscle or joint) pain Rare ( *1/10,000, <1/1,000)
Osteonecrosis of the jaw (see section 4.4)
During post-marketing experience the following reactions have been reported (frequency rare):
Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction)
Neurological: headache.
Uncommon ( *1/1,000, <1/100)
Body as a whole: rash, pruritus, erythema
Gastro-intestinal: nausea, vomiting, gastritis, oesophagitis*, oesophageal erosions*, melaena.
Rare ( *1/10,000, <1/1,000)
Body as a whole: hypersensitivity reactions including urticaria and angioedema. Transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically in association with initiation of treatment. Rash with photosensitivity. Symptomatic hypocalcaemia, often in association with predisposing conditions (see 4.4 'Special warnings and precautions for use').
Gastro-intestinal: oesophageal stricture*, oropharyngeal ulceration*, upper gastrointestinal PUBs (perforation, ulcers, bleeding), although a causal relationship cannot be ruled out.
Special senses: uveitis, scleritis, episcleritis.
Isolated cases of severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
* See 4.4 'Special warnings and precautions for use' and 4.2 'Posology and method of administration'.
Laboratory test findings
In clinical studies, asymptomatic, mild and transient decreases in serum calcium and phosphate were observed in approximately 18 and 10%, respectively, of patients taking alendronate 10 mg/day versus approximately 12 and 3% of those taking placebo. However, the incidences of decreases in serum calcium to <8.0 mg/dl (2.0 mmol/1) and serum phosphate to ^ 2.0 mg/dl (0.65 mmol/1) were similar in both treatment groups.
4.9 Overdose
Hypocalcaemia, hypophosphataemia and upper gastro-intestinal adverse events, such as upset stomach, heartburn, oesophagitis, gastritis, or ulcer, may result from oral overdosage.
No specific information is available on the treatment of overdosage with alendronate. Milk or antacids should be given to bind alendronate. Owing to the risk of oesophageal irritation, vomiting should not be induced and the patient should remain fully upright.
SUMMARY OF PRODUCT CHARACTERISTICS
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Bisphosphonate, for the treatment of bone diseases.
ATC Code: M05B A04......
• FIT 2: A four-year study of 4,432 patients with low bone mass but without a baseline vertebral fracture. In this study, a significant difference was observed in the analysis of the subgroup of osteoporotic women (37% of the global population who correspond with the above definition of osteoporosis) in the incidence of hip fractures (alendronate 1.0% vs. placebo 2.2%, a reduction of 56%) and in the incidence of 1 vertebral fracture (2.9% vs. 5.8%, a reduction of 50%).
Paediatric patients: Alendronate sodium has been studied in a small number
of patients with osteogenesis imperfecta under the age of 18 years. Results are insufficient to support the use of alendronate sodium in paediatric patients with osteogenesis imperfecta.
5.2 Pharmacokinetic properties
Absorption
Relative to an intravenous reference dose, the oral mean bioavailability of alendronate in women was 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and two hours before a standardised breakfast. Bioavailability was decreased similarly to an estimated 0.46% and 0.39% when alendronate was administered one hour or half an hour before a standardised breakfast. In osteoporosis studies, alendronate was effective when administered at least 30 minutes before the first food or beverage of the day.
Bioavailability was negligible whether alendronate was administered with, or up to two hours after, a standardised breakfast. Concomitant administration of alendronate with coffee or orange juice reduced bioavailability by approximately 60%.
In healthy subjects, oral prednisone (20 mg three times daily for five days) did not produce a clinically meaningful change in oral bioavailability of alendronate (a mean increase ranging from 20% to 44%).
Distribution
Studies in rats show that alendronate transiently distributes to soft tissues following 1 mg/kg intravenous administration but is then rapidly redistributed to bone or excreted in the urine. The mean steady-state volume of distribution, exclusive of bone, is at least 28 litres in humans. Concentrations of drug in plasma following therapeutic oral doses are too low for analytical detection (<5 ng/ml). Protein binding in human plasma is approximately 78%.
Biotransformation
There is no evidence that alendronate is metabolised in animals or humans.
Elimination
Following a single intravenous dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the faeces. Following a single 10 mg intravenous dose, the renal clearance of alendronate was 71 ml/min, and systemic clearance did not exceed 200 ml/min. Plasma concentrations fell by more than 95% within six hours following intravenous administration. The terminal half-life in humans is estimated to exceed ten years, reflecting release of alendronate from the skeleton. Alendronate is not excreted through the acidic or basic transport systems of the kidney in rats, and thus it is not anticipated to interfere with the excretion of other medicinal products by those systems in humans.
Characteristics in patients
Preclinical studies show that the drug that is not deposited in bone is rapidly excreted in the urine. No evidence of saturation of bone uptake was found after chronic dosing with cumulative intravenous doses up to 35 mg/kg in animals. Although no clinical information is available, it is likely that, as in animals, elimination of alendronate via the kidney will be reduced in patients with impaired renal function. Therefore, somewhat greater accumulation of alendronate in bone might be expected in patients with impaired renal function (see 4.2 'Posology and method of administration').
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. Studies in rats have shown that treatment with alendronate during pregnancy was associated with dystocia in dams during parturition which was related to hypocalcaemia. In studies, rats given high doses showed an increased incidence of incomplete foetal ossification. The relevance to humans is unknown.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose Crospovidone Magnesium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
36 months
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Al/Al blisters
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Strandhaven Limited T/A Somex Pharma
600 High Road
Seven Kings
Ilford
Essex
IG3 IBS
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 15764/0032
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
26/10/2007
10 DATE OF REVISION OF THE TEXT
04/04/2013
11 DOSIMETRY (IF APPLICABLE)
INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)