INSTRUCTION
For medical use of preparation
ALENDRA®
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Composition: Pharmaceutical Form: Tablets Pharmacotherapeutic group. Bisphosphonate, for the treatment of bone diseases. Drugs that influence on bone structure and mineralization. Code ATC M05B A04. Clinical characteristics.
Alendronate reduces the risk of vertebral and hip fractures. |
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Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
Contraindications.
Hypersensitivity to Sodium Alendronate or other drug ingredient; inability to stand or sit upright for at least 30 min after drug intake; hypocalcemia; oesophagus involvement, which delay oesophageal empting, such as stricture or achalasia of oesophagus; severe renal insufficiency (creatinine clearance < 35 ml/min); concomitant usage with other bisphosphonates; pregnancy and lactation period; children under 18 years old.
Administration and Dosage.
The medicine should be taken immediately on getting up, swallowing the tablet as whole and without chewing or dissolving, with full glass of water only for at least 30 min before your first meal, water or other drugs of a day. Other beverages, food or drugs can decrease the absorption of alendronate. One should never lie down for at least 30 min and until after your first food of a day to decrease an irritant action on oesophagus. Do not take the drug before going to bed or before getting up or lying down in horizontal position after taking the drug. Failure to follow this instruction may increase the risk of oesophageal side effects.
In addition to the drug treatment it is recommended to change a way of life for patients with osteoporosis – to stop smoking, to limit taking alcohol, to do exercises, to stick to calcium diet.
The recommended dose for osteoporosis treatment in postmenopausal women and men is 1 tablet (10 mg) per a day or 1 tablet (70 mg) per a week. It is also prescribed with calcium supplements in dose 0.5 g of calcium per a day. The treatment lasts for a long time – for years. The recommended dose for osteoporosis prophylaxis in postmenopausal women is 5 mg per a day. For the treatment and prophylaxis of glucocorticoid-induced osteoporosis in men and women the recommended dosage is 5 mg once per a day, except for postmenopausal women not receiving estrogens, for which the recommended dosage is 10 mg once per a day. Appropriate pharmaceutical form and dosage of the preparation should be used during administration of the dosage of 5 mg.
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 GFR greater than 35 ml/min. Alendronate is not recommended for patients with renal impairment where GFR is less than 35 ml/min, due to lack of experience.
Use in children: (under 18 years):
Alendronate has not been studied in a small number of patients with osteogenesis imperfecta under 18 years of age. Results are insufficient to support its use in children.
Side effects:
The following gastrointestinal adverse reactions can appear: heartburn, nausea, vomiting, acid eructation, epigastric pain, dyspepsia, dysphagia, meteorism, abdominal swelling, constipation, diarrhoea, melena; rarely- oesophagitis, oesophageal erosions and oesophageal ulcers; in isolated cases stenosis and oesophagus perforation, oropharynx ulcers, gastric ulcer and duodenal ulcer were observed.
In single cases the following allergic reactions may occur: skin rash, hyperaemia, itch, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria and in isolated cases – angioneurotic edema.
In some patients who took the preparation there were noted asymptomatic hypocalcemia and hypophosphatemia, headache, myalgia, musculoskeletal (bone, muscle or joint) pain, muscle cramp, sometimes – uveitis, scleritis or episcleritis.
Very rarely- 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 test findings
In clinical studies, asymptomatic, mild and transient decreases in serum calcium and phosphate were observed in approximately 18 and 10%, respectively, of patients taking alendronate 10 mg/day versus approximately 12 and 3% of those taking placebo. However, the incidences of decreases in serum calcium to <8.0 mg/dl (2.0 mmol/l) and serum phosphate to 
2.0 mg/dl (0.65 mmol/l) were similar in both treatment groups.
Overdosage.
Symptoms: hypocalcaemia, hypophosphatemia, stomach upset, heartburn, oesophagitis, gastritis or gastric ulcer.
Treatment. Milk or antacids should be given to bind alendronate. Due to risk of oesophageal irritation, vomiting should not be induced and the patient should remain fully upright.
Special warnings and precautions for usage
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 tract other than pyloroplasty .
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 (post-marketing) 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).
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.
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 'Alendronate' 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 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 'Alendronate'.
Due to the 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 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.
Peculiarities in usage.
- Take the medicine as soon as you get up for the day 30 min before your first meal in sitting or standing position only.
- Drink full glass of plain water after Alendra® tablet because any other beverage will decrease absorption of this drug (Do not use mineral water).
- Do not chew or dissolve the tablets because of risk of oropharynx ulceration.
- Do not lie down for at least 30 min after taking the medicine (do not take this drug if you are not in sitting or upright standing position for 30 min). Taking medicine in lying position or at bedtime increases the risk of oesophagitis development (mucous coat esophagitis).
- Interval between taking Sodium Alendronate and other medicine taken per oral should not be less than 1 hour.
- The drug should be carefully used in patients with acute upper gastrointestinal diseases (dysphagia, oesophagus diseases, gastritis, duodenitis, and ulcers) because of possible irritant action of Alendra® on mucus.
- Treatment by the preparation should be combined with calcium-fortified diet. Patients should receive additionally about 0.5 g of calcium per a day, except in the cases of hypercalcemia (malignant or medicament) treatment.
- The calcium supplements and the products contained calcium should not be taken for 1–2 hours after intake of Alendronate, because calcium delays Alendronate (and other bisphosphonates) absorption from intestine.
- In case of once a week dosage schedule, choose the day of week which best fits your schedule. Every week, take one tablets on the same day of week which you have chosen.
- If you miss a dose, take only one tablet in the next morning after you remember. Do not take two tablets on the same day. Then use the drug as usual – take next one tablet the day you have chosen according your schedule of the treatment.
In case of appearance of oesophagus disease symptoms (such as complications or pain upon swallowing, chest pain, new or worsening heartburn) you should stop the preparation usage and make an additional examination).
Before the beginning of the therapy by Alendra® patients with hypocalcaemia and other mineral metabolism disorders (such as vitamin D deficiency) should get appropriate treatment because level of serum calcium and phosphates may decrease during the Alendronate treatment.
The usage of Alendronate can be combined with supplemental vitamin D.
There is no need to correct the dosage for elderly patients and patients with renal insufficiency from mild to moderate (creatinin clearance from 35 to 60 ml/min).
Influence on ability to drive car and work with dangerous machines.
There are no data concerning the influence of Alendra® on ability to drive car and other machines.
Drug interaction and other types of interactions.
The absorption of Alendronate is decreased in case of concomitant usage with calcium supplement (including food supplements) and antacids. An interval between the preparation intake and other per oral drugs usage must be not less than 1 hour.
Combined usage of Sodium Alendronate and hormone replacement therapy (estrogens + progesterones) caused more bone weight increase and more significant bone rosorption decrease in comparison with the individual usage of the first and second treatment metods.
NSAIDs increase gastrointestinal action of Sodium Alendronate.
Since NSAID use is associated with gastrointestinal irritation, caution should be used during concomitant use with Alendronate
Increase of hypocalcaemia is possible during simultaneous Sodium Alendronate usage with glucocorticoids can because they suppress the vitamin D activity that results in decrease of absorption of calcium and its more active excretion.
It is recommended to be on guard in case of usage of Alendronate with aminoglycosides, which decrease calcium level in serum for a long time.
The usage of thiazides, which decrease the calcium elimination with urine, can interfere with the calcium decreasing effect of Alendronate in the treatment of malignant hypercalcemia treatment.
Pregnancy and lactation
Alendronate should not be used during pregnancy and lactation.
Pharmacological properties.
Pharmacodynamics. Sodium Alendronate is one of the aminobisphosphonates group. It is a synthetic analogue of nature pyrophosphate. It inhibits precipitation of calcium phosphate, blocks its transformation into hydroxyapatite, delays the aggregation of apatite crystals with formation of bigger crystals and accelerates resolution of these crystals. Selective action is caused by high affinity of bisphosphonates and mineral components of bone. It acts as effective non-hormonal specific inhibitor of osteoclast mediated bone resorption. Accurate mechanisms of this process are not still cleared up. It promotes positive balance of resorption and bone renovation. It increases a mineral density of the spine, pelvic and other bones, promotes the formation of bone tissue with normal histological structure. It prevents new bone fractures. It decreases the calcium level in serum as a result of inhibition of bone resorption and decrease of calcium release from bone tissue. The preparation action of calcium decrease, mediated as a result of osteoclast inhibition, is observed in1–2 days.
Pharmacokinetics. 25% of Sodium Alendronate is absorbed gastro intestinal tract. Absolute bioavailability of tablets (from 5 to 10 mg) has taken an empty stomach before 2 hours to a meal is 0.64% (for women) and 0.59% (for men). Bioavailability decreases (approximately on 40%) in Alendronate intake before half an hour–hour before usual breakfast. Alendronate bioavailability is small while its usage with a meal or during two hours after a meal. Simultaneous usage of Alendronate with other beverages (including mineral water, coffee, Orange juice) decreases its bioavalability to 60%. Trials conducted on laboratory rats show that in intravenous introduction of the drug in dosage 1 mg/kg Alendronate is temporarily distributed in soft tissues and then quickly is redistributed.
Very small amount <1% of ingested from, therefore, it is very important to follow the instruction regarding how to take the tablets. The half of absorbed dose is mainly eliminated unchanged through kidneys over 72 hours, and the rest is sequestered in bone tissues for a long time and is eliminated extremely slowly as a result of strong bonding with bone tissue. Half-excretion period of Alendronate from bones is several years.
Approximately 78% of Alendronate binds with plasma proteins and is not metabolized. The preparation concentration in plasma is small (less than 5 ng/ml) and is decreasing to 95% during 6 hours after intravenous infusion.
After single oral introduction of 10 mg of Alendronate its renal clearance was 71 ml/min and systemic clearance did not exceed 200 ml/min.
Pharmaceutical characteristics.
General physic-chemical properties: round, biconvex, white or nearly white tablets (10 mg) or oval, biconvex, white or nearly white tablets (70 mg).
Shelf life.
3 years.
Storage.
Keep it out of reach of children, in dry place at a temperature not more 25°C.
Package.
Tablets (10 mg). There are 10 tablets in blister, there are 3 blisters in a carton box № 30 (10x3).
Tablets 70 mg. There are 4 tablets in blister, each blister is in a carton envelop № 4.
Conditions of supply.
By prescription.
Manufacturer.
Kusum Healthcare Pvt. Ltd or Liva Healthcare Ltd.
Address.
SP 289 (A), RIICO INDL. AREA, CHOPANKI, BHIWADI (Raj.), (India).
A/52, MALEGAON, M.I.D.C., SINNAR, DIST. NASHIK, INDIA.
First deputy director of
State Pharmacological Centre of
MH of Ukraine
M.D., Prof. A. M. Morozov