Each tablet contains 70mg alendronic acid (as sodium alendronate trihydrate)

Tablet. White to off-white, oval tablet, embossed "AN 70" on one side and the “Arrow logo” on the other.

Treatment of post-menopausal osteoporosis.

Alendronate reduces the risk of vertebral and hip fractures.

For oral use.

The recommended dose is one 70 mg tablet per week.

To obtain satisfactory absorption of alendronate

Alendronic acid 70mg tablets must be taken on an empty stomach immediately on rising in the morning, with plain water only, at least 30 minutes before the first food, drink or other medication of the day. Other drinks (including mineral water), food and some medicines are likely to reduce the absorption of alendronate.

To assist delivery to the stomach and thus reduce the risk of irritation/side effects locally and in the oesophagus.

• Alendronic acid 70mg tablets should only be swallowed on arising for the day with a whole glass of water (not less than 200 ml or 7 fl. oz).
• Alendronic acid 70mg tablets should be swallowed whole. The tablets should not be chewed, sucked or allowed to dissolve in the mouth on account of the risk of oropharyngeal ulceration.
• Patients should not lie down until after the first meal of the day, which must be at least 30 minutes after taking the tablet.
• Patients should not lie down within 30 minutes of taking Alendronic acid 70mg tablets
• Alendronic Acid 70mg tablets should not be taken at bedtime or before arising for the day.

Patients should be given a calcium and vitamin D supplement if the diet is inadequate.

Use in elderly patients: In clinical trials there was no age-related difference with regard to efficacy or safety profiles of alendronate. Therefore no adjustment of the dose is necessary for elderly patients.

Use in impaired renal function: No dose adjustment is necessary in patients with a glomerular filtration rate (GFR) greater than 35 ml/min. Alendronate is not recommended for patients with impaired renal function if the GFR is less than 35 ml/min, as there is no experience of this.

Use in impaired hepatic function

No dose adjustment is necessary.

Use in children: Alendronate has not been studied in children and should not be given to them.

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

• Oesophageal abnormalities and other factors that delay oesophageal emptying, such as stricture or achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Hypersensitivity to alendronate, other bisphosphonates or to any of the excipients.
• Hypocalcaemia.

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 gastrointestinal tract other than pyloroplasty.

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. 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 (postmarketing) reports of gastric and duodenal ulcers, some severe and with complications.

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.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene, periodontal disease, smoking).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Atypical stress fractures

Stress fractures (also known as insufficiency fractures) of the proximal femoral shaft have been reported in patients treated long-term with alendronic acid (time to onset ranged from 18 months to 10 years). The fractures occurred after minimal or no trauma and some patients experienced thigh pain weeks to months before presenting with a completed femoral fracture. Fractures were 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 was also reported. Discontinuation of bisphosphonate therapy in patients with stress fracture is advisable pending evaluation of the patient, based on an individual benefit/risk assessment.

Bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. In postmarketing experience, these symptoms have rarely been severe and/or incapacitating.

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.

Patients should be instructed that if they miss a dose of Alendronic Acid 70mg 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.

Alendronate is not recommended for patients with renal impairment where GFR is less than 35 ml/min.

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

Hypocalcaemia must be corrected before initiating therapy with alendronate.

Other disorders affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) should also be effectively treated. In patients with these conditions, serum calcium and symptoms of hypocalcaemia should be monitored during therapy with Alendronic Acid 70mg Tablets.

Due to the 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 have occasionally 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 particularly important in patients receiving glucocorticoids.

Excipients

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

If taken at the same time, it is likely that foods and drinks (including mineral water), calcium supplements, antacids and some oral medicines will affect the absorption of alendronate. Patients must therefore wait for at least 30 minutes after taking alendronate before taking any other oral medicine.

No other clinically significant drug interactions are expected. A number of patients in the clinical trials received oestrogen (intravaginally, transdermally or orally) concomitantly with alendronate. No undesirable effects could be related to the combination treatment.

No specific interaction studies have been carried out, but alendronate was used in clinical trials concomitantly with a number of other commonly prescribed medicines without any evidence of clinically unfavourable interactions.

In a one-year study in post-menopausal women with osteoporosis the overall safety profiles for alendronate once-weekly tablets (n=519) and alendronate 10 mg daily (n=370) were similar.

In two three-year studies of almost identical design, with post-menopausal women (alendronate 10 mg: n=196; placebo: n= 397) the overall safety profiles for alendronate 10 mg daily and placebo were similar.

Undesirable effects reported by the investigators as possibly, probably or definitely related to the drug are presented below if they occurred in 1 % of any in the treatment groups in the one-year study or in 1 % of the patients who were treated with alendronate 10 mg per day and with an incidence higher than in patients who were treated with placebo in three-year studies.

The following undesirable effects have also been reported in clinical trials and/or post marketing:

Nervous system disorders:

Common ( 1/100, <1/10): Headache

Eye disorders:

Rare ( 1/10,000, <1/1000): Uveitis, scleritis

Gastrointestinal disorders:

Common ( 1/100, <1/10): Abdominal pain, dyspepsia, constipation, diarrhoea, flatulence, oesophageal ulcers, dysphagia, abdominal distension, acid regurgitation.

Uncommon ( 1/1000, <1/100): Nausea, vomiting, gastritis, oesophagitis oesophageal erosions, melaena.

Rare ( 1/10,000, <1/1000): Oesophageal stricture, oropharyngeal ulceration, upper gastrointestinal PUB (perforations, ulcers, bleeding), a causal relationship cannot be ruled out.

Skin and subcutaneous tissue disorders:

Very rare (1/10,000): Isolated cases of severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.

Musculoskeletal, connective tissue and bone disorders:

Common ( 1/100, <1/10): Musculoskeletal pain (bones, muscles or joints)

Unknown frequency: Osteonecrosis

General disorders and administration site conditions:

Uncommon ( 1/1000, <1/100): Rash, pruritus, erythema.

Rare ( 1/10,000, <1/1000): Hypersensitivity reactions including urticaria and angioedema. Transient symptoms as in an acute phase reaction (myalgia, malaise and in rare cases fever) usually in connection with the start of treatment. Skin rash with photosensitivity. Symptomatic hypocalcaemia, generally in connection with predisposing conditions.

Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the reports refer to cancer patients, but such cases have also been reported in patients treated for osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and / or local infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids and poor oral hygiene are also deemed as risk factors.

Laboratory values: In clinical trials, asymptomatic, slight and transient decreases in serum calcium and serum phosphate were observed in approx. 18 and 10 % respectively of the patients taking alendronate 10 mg/day versus 12 and 3 % respectively of those taking placebo. However, the incidence of reductions in serum calcium to <2.0 mmol/l and serum phosphate to 0.65 mmol/l was comparable in the two groups.

Winthrop Pharmaceuticals UK Ltd

POM

22 November 2011