MAXLEN-70 Tablet

- Treatment and prevention of postmenopausal Osteoporosis.

- Treatment to increase bone mass in men with osteoporosis.

Posology and Method of Administration

1 tablet once weekly.

To permit adequate absorption of alendronate:

Maxlen-70 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.

To facilitate delivery to the stomach and thus reduce the potential for local and oesophageal irritation/adverse experiences:

Maxlen-70 should only be swallowed upon arising for the day with a full glass of water (not less than 200mL or 7fl.oz.).

Patients should not chew the tablet or allow the tablet to dissolve in their months 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 Maxlen-70.

Maxlen-70 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.

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 GRF greater than 35mL/min. Alendrone is not recommended for patients with renal impairment where GFR is less than 35mL/min, due to lack of experience.

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

- 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 “Special warnings and precautions for use”.

Immune systems 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

Eye disorders:

Rare: uveitis, scleritis, episcleritis

Gastrointestinal disorders:

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

Uncommon: nausea, vomiting, gastritis, oesophagitis, oropharyngeal ulceration, upper gastrointestinal PUBs (perforation, ulcers, bleeding).

Skin and subcutaneous tissue disorders:

Uncommon: rash, pruritus, erythema

Rare: rash with photosensitivity

Very rare isolated cases: isolated cases of severe skin reactions including Stevens Johnson syndrome and toxic epidermal necrolysis.

Musculoskeletal, connective tissue and bone disorders:

Common: musculoskeletal (bone, muscle or joint) pain

Rare: osteonecrosis of the jaw has been reported in patients treated by bisphosphonates.

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 “Posology and method of administration” and “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 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.

Pregnancy

There are no adequate data for the use of alendronate in pregnant women.

Lactation

It is not known whether alendronate is excreted into human breast milk. Given the indication, alendronate should not be used by breast-feeding women.

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 bleeding, or surgery of the upper gastro-intestinal tract other than pyloroplasty.

Oesophageal reactions (sometimes severe and requiring hospitalization), such as oesophagitis, oesophageal ulcers and oesophageal erosions, rarely followed by oesophagitis stricture, have been reported in patients receiving alendronate. Physicians should therefore be alert to any signs or symptoms signaling 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 ‘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 bad and with complications. A causal relationship cannot be ruled out.

Osteonecrosis of the jaw generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimen 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).

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 judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

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. 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 Maxlen-70 once weekly, they should take 1 tablet on the morning after they remember. They should take 2 tablets on the same day but should return to taking 1 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 35mL/min (see “Posology and method of administration”).

Causes of osteoporosis other than oestrogen deficiency and ageing should be considered. Hypocalcaemia must be corrected before initiating therapy with alendronate (see “Contraindications”).

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 “Maxlen-70”. Due to positive effects of alendronate in increasing bone mineral, decreases in serum calcium and phosphate may occur. These are usually small and asymptomatic. However, there have been 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 particularly important in patients receiving glucocorticoids.

MAXLEN-70 is a bisphosphonate that acts as a specific inhibitor of osteoclast mediated bone resorption. Bisphosphonates are synthetic analogs of pyrophosphate that bind to the hydroxyapatite found in bone.

Pharmacotherapeutic group: Bisphosphonate, for the treatment of bone diseases.

The active ingredient of Maxlen-70, alendronate sodium trihydrate, is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect on bone formation. Preclinical studies have shown preferential localization of alendronate to sites of active resorption. Activity of osteoclasts is not affected. The bone formed during treatment with alendronate is of normal quality.