ALENDRONIC ACID ONCE WEEKLY

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 once weekly tablet, 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. 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 Once Weekly 70 mg on an individual patient basis, particularly after 5 or more years of use. Elderly In clinical studies there was no age-related difference in the efficacy or safety profiles of alendronic acid.

Therefore no dosage adjustment is necessary for the elderly. Renal impairment No dosage adjustment is necessary for patients with GFR greater than 35 ml/min. Alendronic acid Tablet is not recommended for patients with renal impairment where GFR is less than 35 ml/min, due to lack of experience.

1). Alendronic acid Once Weekly 70 mg has not been investigated in the treatment of glucocorticoid-induced osteoporosis. Method of administration Oral use.

To permit adequate absorption of alendrnic acid:

Alendronic acid Tablet must be taken at least 30 minutes before the first food, beverage, or medicinal product of the day with plain water only. 5). 4): • Alendronic acid Tablet should only be swallowed upon arising for the day with a full glass of water (not less than 200 ml or 7 fluid ounce).

• Patients should not chew or crush 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. • Alendronic acid Tablet should not be taken at bedtime or before arising for the day. 4).

In a one-year study in post-menopausal women with osteoporosis the overall safety profiles of Alendronic acid tablet 70 mg (n=519) and alendronic acid tablet 10 mg/day (n=370) were similar. In two three-year studies of virtually identical design, in post-menopausal women (alendronic acid tablet 10 mg: n=196, placebo: n=397) the overall safety profiles of alendronic acid tablet 10 mg/day and placebo were similar.

5 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), not known (cannot be estimated from the available data).

System Organ Class Frequency Adverse Experience Term Immune system disorders:

Rare hypersensitivity reactions including urticaria and angioedema Metabolism and nutrition disorders: Rare symptomatic hypocalcaemia, often in association with predisposing conditions§.

Common headache, dizziness† Nervous system disorders:

Uncommon dysgeusia† Eye disorders: Uncommon eye inflammation (uveitis, scleritis or episcleritis) Common vertigo† Ear and labyrinth disorders: Very rare osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction) Common: abdominal pain, dyspepsia, constipation, diarrhoea, flatulence, oesophageal ulcer*, dysphagia*, abdominal distension, acid regurgitation Uncommon: nausea, vomiting, gastritis, oesophagitis*,oesophageal erosions*, melena† Gastro-intestinal disorders: Rare: oesophageal stricture*, oropharyngeal ulceration*, upper gastro-intestinal PUBs (perforation, ulcers, bleeding)§ Common: alopecia†, pruritus† Uncommon: rash, erythema Skin and subcutaneous tissue disorders: Rare: rash with photosensitivity, severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis‡ Very common: musculoskeletal (bone, muscle or joint) pain which is sometimes severe†§ Common: joint swelling† Rare: osteonecrosis of the jaw‡§; atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction) Musculoskeletal and connective tissue disorders: Not known atypical fracture of other bones Common: asthenia†, peripheral oedema† General disorders and administration site conditions: Uncommon: transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically in association with initiation of treatment†.

4 †Frequency in Clinical Trials was similar in the medicinal product and placebo group. 4 ‡This adverse reaction was identified through post-marketing surveillance. The frequency of rare was estimated based on relevant clinical trials.

Description of selected adverse reactions Atypical subtrochanteric and diaphyseal femoral fractures Although the pathophysiology is uncertain, consistent evidence from epidemiological studies suggests an increased risk of atypical subtrochanteric and diaphyseal femoral fractures with long-term bisphosphonate therapy for postmenopausal osteoporosis, particularly beyond three to five years of use.

The absolute risk of atypical subtrochanteric and diaphyseal long bone fractures (bisphosphonate class adverse reaction) remains rare. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorization of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Upper gastrointestinal adverse reactions Alendronic acid can cause local irritation of the upper gastro-intestinal mucosa. 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 or perforation, have been reported in patients receiving alendronic acid.

8). The risk of severe oesophageal adverse experiences appears to be greater in patients who fail to take alendronic acid properly and/or who continue to take alendronic acid tablet after developing symptoms suggestive of oesophageal irritation.

2). Patients should be informed that failure to follow these instructions may increase their risk of oesophageal problems. 8). Osteonecrosis of the jaw Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer who are 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. The following risk factors should be considered when evaluating an individual's risk of developing osteonecrosis of the jaw: • potency of the bisphosphonate (highest for zoledronic acid), route of administration (see above) and cumulative dose • cancer, chemotherapy, radiotherapy, corticosteroids, angiogenesis inhibitors, smoking • a history of dental disease, poor oral hygiene, periodontal disease, invasive dental procedures and poorly fitting dentures.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with oral bisphosphonates in patients with poor dental status. 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. During bisphosphonate 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.

Osteonecrosis of the external auditory canal Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma.

The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms such as pain or discharge, or chronic ear infections. Musculoskeletal pain Bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates.

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 treatment. A subset had recurrence of symptoms when rechallenged with the same medicinal product 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 complete 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 […]

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.