Maxlen

MAXLEN-70 is a cylindrical white tablet with a one face groove.
Each tablet contains Alendronate Sodium trihydrate 91.37 mg equivalent to Alendronic acid 70 mg.
MAXLEN-70 (Alendronic Acid) 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.
Alendronic Acid is chemically described as (4-amino-1hydroxybutylidene) bisphosphonic acid monosodium salt trihydrate.
Excipients/Inactive Ingredients: Sorbitol, Maize Starch, Sodium Starch Glycollate, Stearic Acid, Magnesium Stearate.

Pharmacotherapeutic group: Bisphosphonate, for the treatment of bone diseases.
Pharmacology: Pharmacodynamics: 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 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.
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 once weekly 70 mg (n=519) and alendronate 10 mg daily (n=370) was demonstrated in a one-year multicentre study of post-menopausal 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.
Pharmacokinetics: Absorption and Bioavailability: 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 standardized 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 standardized breakfast.
Distribution: 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%.
Metabolism and Elimination: Biotransformation: There is no evidence that alendronate is metabolized in animals or humans.
Elimination: 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.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

Treatment and prevention of postmenopausal osteoporosis.
Treatment to increase bone mass in men with osteoporosis.
Treatment of glucocorticoid induced osteoporosis in men and women.

The recommended dosage is one 70 mg 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 (see Interactions).
To facilitate delivery to the stomach and thus reduce the potential for local and oesophageal irritation/adverse experiences (see Precautions).
Maxlen-70 should only be swallowed upon arising for the clay 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 at least 30 minutes after taking Maxlen-70 and until after their first food of the day.
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 (see Precautions).
Use in special populations: 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 creatinine clearance greater than 35 ml/min. Alendronate is not recommended for patients with renal impairment where creatinine clearance is less than 35 ml/min.
Use in children: Alendronate has not been studied in children and should not be given to them.

Hypocalcemia, hypophosphataemia and upper gastro-intestinal adverse events, such as upset stomach, heartburn, oesophagitis, gastritis, or ulcer, may result oral over dosage.
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.

Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia.
Inability to stand or sit up right for at least 30 minutes.
Hypersensitivity to alendronate or to any of the excipients.
Hypocalcaemia.
See also Precautions.

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 taken 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 (see Contraindications).
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 Dosage & Administration). Patients should be informed that failure to follow these instructions may increase their risk of oesophageal problems.
Osteonecrosis of the jaw generally associated with tooth extraction and/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 (see Adverse Reactions). 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 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 creatinine clearance is less than 35 ml/min (see Dosage & 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. hypoparathyrodism, vitamin D deficiency and calcium malabsorption). Ensuring adequate calcium and vitamin D intake is particularly important in patients receiving glucocorticoids.
Effects on Ability to Drive and Operate Machine: No effects on ability to drive and use machines have been observed.

There are no adequate data for the use of alendronate in pregnant women.
It is not known whether alendronate is excreted into human breast milk. Given the indication, alendronate should not be used by breast-feeding women.

The following adverse experiences have also been reported.
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 systems disorders: Rare: hypersensitivity reactions including urticaria and angioedema.
Metabolism and nutrition disorders: Common: 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, diarrhea, flatulence, oesophageal ulcer*, dysphagia*, abdominal distension, acid regurgitation.
Uncommon: nausea, vomiting, gastritis, oesophagitis*, oropharyngeal ulceration*, upper gastrointestinal PUBs (perforation, ulcers, bleeding).
*See Dosage & Administration and Precautions.
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 Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
No other interactions with medicinal products of clinical significance ace anticipated. A number of patients in the clinical trials received oestrogen (intravaginal, transderrnal 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.

Protect from light & moisture. Store at or below 30°C.
Shelf Life: 3 years.

Agents Affecting Bone Metabolism

M05BA04 - alendronic acid ; Belongs to the class of bisphosphonates. Used in the treatment of bone diseases.

D