Alendronic Acid 70 mg Tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Alendronic Acid 70 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 70 mg alendronic acid (as alendronate sodium trihydrate). For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet.

White oval, biconvex tablet, engraved “ALE70” on one side and plain on the other side.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of postmenopausal osteoporosis. Alendronic Acid 70 mg Tablets reduce the risk of vertebral and hip fractures.

4.2 Posology and method of administration

Posology

The recommended dosage is one 70 mg tablet once weekly.

Missed dose

Patients should be instructed that if they miss a dose of Alendronic Acid 70 mg Tablets, they should take one tablet on the morning after they remember. They should not take two tablets on the same day but should return to taking one tablet once a week, as originally scheduled on their chosen day.

To permit adequate absorption of alendronate:

Alendronic Acid 70 mg Tablets 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'):

• Alendronic Acid 70 mg Tablets 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 Alendronic Acid

  70 mg Tablets

• Alendronic Acid 70 mg Tablets 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. Alendronic Acid 70 mg Tablets are not recommended for patients with renal impairment where GFR is less than 35 ml/min, due to lack of experience.

Use in children (under 18 years): Alendronate has been studied in a small number of patients with osteogenesis imperfecta under 18 years of age. Results are insufficient to support its use in children

Alendronic Acid 70 mg Tablets have not been investigated in the treatment of glucocorticoid-induced osteoporosis.

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of alendronic acid on an individual patient basis, particularly after 5 or more years of use.

Method of administration

Oral use.

4.3 Contraindications

• Hypersensitivity to the active substance alendronate or to any of the excipients listed in section 6.1.
• 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.
• Hypocalcaemia.

4.4 Special warnings and precautions for use

Upper gastrointestinal adverse reactions

Alendronate can cause local irritation of the upper gastro-intestinal mucosa. Because there is a potential for worsening of the underlying disease, caution should be used when alendronate is given to patients with active upper gastro-intestinal problems, such as dysphagia, oesophageal disease, gastritis, duodenitis, ulcers, or with a recent history (within the previous year) of major gastro-intestinal disease such as peptic ulcer, or active gastro-intestinal bleeding, or surgery of the upper gastro-intestinal tract other than pyloroplasty (see section 4.3).

In patients with known Barrett’s oesophagus, prescribers should consider the benefits and potential risks of alendronate on an individual patient basis.

Oesophageal reactions (sometimes severe and requiring hospitalisation), such as oesophagitis, oesophageal ulcers and oesophageal erosions, rarely followed by oesophageal stricture, have been reported in patients receiving alendronate. Physicians should therefore be alert to any signs or symptoms signalling a possible oesophageal reaction and patients should be instructed to discontinue alendronate and seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing or retrosternal pain, new or worsening heartburn.

The risk of severe oesophageal adverse experiences appears to be greater in patients who fail to take alendronate properly and/or who continue to take alendronate after developing symptoms suggestive of oesophageal irritation. It is very important that the full dosing instructions are provided to, and understood by the patient (see 4.2

'Posology and method of administration'). Patients should be informed that failure to follow these instructions may increase their risk of oesophageal problems.

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.

Renal impairment

Alendronate is not recommended for patients with renal impairment where GFR is less than 35 ml/min, (see Section 4.2).

Bone and mineral metabolism

Causes of osteoporosis other than oestrogen deficiency and ageing should be considered.

Hypocalcaemia must be corrected before initiating therapy with alendronate (see 4.3

Contraindications). Other disorders affecting mineral metabolism (such as vitamin

D deficiency and hypoparathyroidism) should also be effectively treated before starting this medicinal product. In patients with these conditions, serum calcium and symptoms of hypocalcaemia should be monitored during therapy with Alendronate Sodium.

Due to positive effects of alendronate in increasing bone mineral, decreases in serum calcium and phosphate may occur especially in patients taking glucocorticoids in whom calcium absorption may be decreased. These are usually small and asymptomatic. However, there have been rare reports of symptomatic hypocalcaemia, which occasionally have been severe and often occurred in patients with predisposing conditions (e.g. hypoparathyroidism, vitamin D deficiency and calcium malabsorption). Ensuring adequate calcium and vitamin D intake is therefore particularly important in patients receiving glucocorticoids.

Atrial fibrillation

The risk of atrial fibrillation in association with bisphosphonate treatment seems to be low, and the balance of risks and benefits for bisphosphonates remains favourable.

To date, clinical trial results have suggested an increased risk of atrial fibrillation possibly for alendronic acid.

The risk of atrial fibrillation with alendronic acid will be kept under close review. Should further evidence accumulate, the product information for alendronic acid will be updated accordingly.

Osteonecrosis of the external auditory canal

The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms, including chronic ear infections, or in patients with suspected cholesteatoma. Possible risk factors include steroid use and chemotherapy, with or without local risk factors such as infection or trauma.

Patients should be advised to report any ear pain, discharge from the ear, or an ear infection during bisphosphonate treatment.

Report any cases of osteonecrosis of the external auditory canal suspected to be associated with bisphosphonates or anyother medicines, including denosumab, on a Yellow Card (https://yellowcard.mhra.gov.uk/).

Osteonecrosis of the jaw

The risk of developing ONJ in association with oral bisphosphonates seems to be low. The risk of ONJ is substantially greater for patients receiving intravenous bisphosphonates for cancer indications than for patients receiving oral bisphosphonates for osteoporosis or Paget’s disease.

There is clear evidence to suggest bisphosphonate-specific and indication specific risk factors such as potency (highest for zoledronate); route of administration (eg, intravenous ibandronte, pamidronate, and zoledronate); and cumulative dose. The evidence base is less robust for other proposed risk factors (eg, duration and type of malignant disease, concomitant treatment, smoking, and comorbid conditions).

However, healthcare professionals should consider these risk factors when evaluating an individual’s risk of developing ONJ.

A history of dental disease—including invasive dental procedures, dental trauma, periodontal disease, and poorly fitting dentures—is associated with an increased risk of ONJ.

All patients with cancer should have a dental check-up before bisphosphonate treatment. All other patients who start bisphosphonates should have a dental examination only if they have poor dental status.

During bisphosphonate treatment, patients should maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain, or swelling.

Musculoskeletal pain

Bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. In post-marketing experience, these symptoms have rarely been severe and/or incapacitating (see section 4.8). The time to onset of symptoms varied from one day to several months after starting treatment. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.

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.

Since NSAID use is associated with gastrointestinal irritation, caution should be used during concomitant use with alendronate.

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 Fertility, pregnancy and lactation

Pregnancy

There are no or limited data from the use of alendronate in pregnant women. Studies in animals have shown reproductive toxicity. Alendronate given during pregnancy in rats caused dystocia related to hypocalcaemia (see section 5.3). Alendronate should not be used during pregnancy.

Breast-feeding

It is unknown whether alendronate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Alendronate should not be used during breast-feeding.

Fertility

Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the dose and duration of bisphosphonate use (see section 5.2). There are no data on foetal risk in humans. However, there is a theoretical risk of foetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied.

4.7 Effects on ability to drive and use machines

Alendronic acid has no or negligible direct influence on the ability to drive and use machines. However, certain adverse reactions (for example blurred vision, dizziness and severe bone, muscle or joint pain (see section 4.8)) that have been reported with Alendronic acid may affect some patients' ability to drive or operate machinery. Individual responses to Alendronic acid may vary.

4.8 Undesirable effects

Summary of the safety profile

In a one-year study in post-menopausal women with osteoporosis the overall safety profiles of Alendronate Sodium 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 drug- 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:

Tabulated list of adverse reactions

The following adverse experiences have also been reported during clinical studies and/or post-marketing use:

Frequencies are defined as:

Very common: (≥1/10)

Common: (≥1/100, <1/10)

Uncommon: (≥1/1,000, <1/100)

Rare: (≥1/10,000, <1/1,000) Very rare: (<1/10,000 including isolated cases)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

Hypocalcaemia, hypophosphataemia and upper gastro-intestinal adverse events, such as upset stomach, heartburn, oesophagitis, gastritis, or ulcer, may result from oral overdosage.

Management

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

Mechanism of action

The active ingredient alendronic acid (as alendronate sodium trihydrate), is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect on bone formation. Preclinical studies have shown preferential localisation of alendronate to sites of active resorption. Activity of osteoclasts is inhibited, but recruitment or attachment of osteoclasts is not affected. The bone formed during treatment with alendronate is of normal quality.

Clinical efficacy and safety

Treatment of post-menopausal osteoporosis

Osteoporosis is defined as BMD of the spine or hip 2.5 SD below the mean value of a normal young population or as a previous fragility fracture, irrespective of BMD.

The therapeutic equivalence of alendronate sodium Once Weekly 70 mg (n=519) and alendronate 10 mg daily (n=370) was demonstrated in a one-year multicentre study of postmenopausal women with osteoporosis. The mean increases from baseline in lumbar spine BMD at one year were 5.1% (95% CI: 4.8, 5.4%) in the 70 mg once- weekly group 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% at the femoral neck and 2.9% and 3.1% at the total hip in the 70 mg once weekly and 10 mg daily groups, respectively. The two treatment groups were also similar with regard to BMD increases at other skeletal sites.

The effects of alendronate on bone mass and fracture incidence in post-menopausal women were examined in two initial efficacy studies of identical design (n=994) as well as in the Fracture Intervention Trial (FIT: n=6,459).

In the initial efficacy studies, the mean bone mineral density (BMD) increases with alendronate 10 mg/day relative to placebo at three years were 8.8%, 5.9% and 7.8% at the spine, femoral neck and trochanter, respectively. Total body BMD also increased significantly. There was a 48% reduction (alendronate 3.2% vs placebo 6.2%) in the proportion of patients treated with alendronate experiencing one or more vertebral fractures relative to those treated with placebo. In the two-year extension of these studies BMD at the spine and trochanter continued to increase and BMD at the femoral neck and total body were maintained.

FIT consisted of two placebo-controlled studies using alendronate daily (5 mg daily for two years and 10 mg daily for either one or two additional years):

• FIT 1: A three-year study of 2,027 patients who had at least one baseline vertebral (compression) fracture. In this study alendronate daily reduced the incidence of 1 new vertebral fracture by 47% (alendronate 7.9% vs. placebo 15.0%). In addition, a statistically significant reduction was found in the incidence of hip fractures (1.1% vs. 2.2%, a reduction of 51%).
• 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%).

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/l) and serum phosphate to ≤2.0 mg/dl (0.65 mmol/l) were similar in both treatment groups.

Paediatric population:

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.

Renal impairment

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

Non-clinical 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

Magnesium stearate

Mannitol powder

Microcrystalline cellulose (PH 102)

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

Clear PVC/PVDC/Al blisters containing 2 or 4 tablets. Pack sizes: 2, 4, 8, 12, 40 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Steranco Healthcare UK Limited

John Eccles House, Robert Robinson Avenue, Oxford Science Park, Oxford,

Oxfordshire OX4 4GP,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 60260/0003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

20/11/2025

10 DATE OF REVISION OF THE TEXT

10/09/2026