Alendronic acid Other names: Alendronate sodium

Magnesium in coadministration with alendronic acid can form non-absorbable complexes.

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. Physicians should therefore be alert to any signs or symptoms signalling a possible oesophageal reaction and patients should be instructed to discontinue alendronic acid and seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing or retrosternal pain, new or worsening heartburn.

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 alendronic acid. Therefore, patients must wait at least 30 minutes after taking alendronic acid before taking any other oral medicinal product.

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

Iron in coadministration with alendronic acid can form non-absorbable complexes.

There are no or limited amount of 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.

Alendronic acid should not be used during pregnancy.

It is unknown whether alendronate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Alendronic acid 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. 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.

Alendronic acid has no or negligible direct influence on the ability to drive and use machines. Patients may experience certain adverse reactions (for example blurred vision, dizziness and severe bone muscle or joint pain) that may influence the ability to drive and use machines.

Summary of the safety profile

In a one-year study in postmenopausal women with osteoporosis the overall safety profiles of alendronic acid 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 postmenopausal 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)

Immune system disorders

Rare: hypersensitivity reactions including urticaria and angioedema

Metabolism and nutrition disorders

Rare: symptomatic hypocalcaemia, often in association with predisposing conditions

Nervous system disorders

Common: headache, dizziness†

Uncommon: dysgeusia†

Eye disorders

Uncommon: eye inflammation (uveitis, scleritis, or episcleritis)

Ear and labyrinth disorders

Common: vertigo†

Very Rare: osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction)

Gastrointestinal disorders

Common: abdominal pain, dyspepsia, constipation, diarrhoea, flatulence, oesophageal ulcer, dysphagia, abdominal distension, acid regurgitation

Uncommon: nausea, vomiting, gastritis, oesophagitis, oesophageal erosions, melena†

Rare: oesophageal stricture, oropharyngeal ulceration, upper gastrointestinal PUBs (perforation, ulcers, bleeding)

Skin and subcutaneous tissue disorders

Common: alopecia†, pruritus†

Uncommon: rash, erythema

Rare: rash with photosensitivity, severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis‡

Musculoskeletal and connective tissue disorders

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)

General disorders and administration site conditions

Common: asthenia†, peripheral oedema†

Uncommon: transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically in association with initiation of treatment†

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