Alendra

Each tablet contains: Alendronic acid 70 mg (equivalent to 91.37 mg alendronate sodium).

Pharmacology: Pharmacodynamics: Alendronate is a bisphosphonate whose main action is to inhibit osteoclast-mediated bone resorption.
Alendronate binds preferentially to active sites of bone resorption where it inhibits the resorptive activity of osteoclasts without inhibiting osteoblast function. Alendronate decreases bone turnover by inhibiting osteoclast action which results in a progressive increase in bone mass and subsequent decrease in osteoporosis-related fractures.
By inhibiting bone resorption, alendronate decreases the concentration of substances released from the bone and leads to significant reductions in plasma calcium and phosphate. This effect may be valuable in severe hypercalcemia, such as that associated with malignancy.
Pharmacokinetics: Alendronate's oral bioavailability is very low and estimated to be about 0.64% in women for doses ranging from 5 to 70 mg and 0.59% in men for 10 mg doses when administered after an overnight fast and two hours before a standardized breakfast.
Food decreases alendronate's bioavailability by about 85-90% while coffee or orange juice reduces absorption by 60%. Taking other medications, especially any calcium-containing compound and multivalent cations, will bind the bisphosphonate and thus also reduce alendronate's absorption. On the other hand, elevation of gastric pH to above 6 will result in a two-fold increase in alendronate absorption. About 60-70% of alendronate absorption occurs within one hour after oral administration.
Alendronate is transiently distributed to soft tissues after absorption. About 60% of the systemic dose is then rapidly redistributed to the bone and 40% is excreted by the kidney.
Alendronate is about 78% bound to plasma protein at pH 7.4, 2.5 mmol/L calcium, and 1 mg/L alendronate concentration. Plasma protein binding is increased with decreasing alendronate concentration and increasing pH and calcium.
Alendronate does not undergo metabolism. After oral administration, about 40% of the absorbed dose is excreted in the urine unchanged within 8 hours then the next 5% of the dose is excreted over the next 64 hours. Renal clearance is comparable to the glomerular filtration rate. Alendronate's biliary elimination is negligible with less than 2% of the administered dose appearing in the feces.
Alendronate's rate of clearance to bone is comparable to that of plasma flow through this tissue and its mean terminal half-life is estimated to exceed 10 years reflecting the amount of alendronate released from the skeleton. Therefore, it is estimated that after 10 years of oral treatment with alendronate 10 mg daily, the amount of alendronate released daily from the skeleton is approximately 25% of the amount absorbed from the gastrointestinal tract.

Treatment of osteoporosis in postmenopausal women and in men.
Prevention of osteoporosis in postmenopausal women.
Note: The optimal duration of use has not been determined. Patients should have the need for continued therapy re-evaluated on a periodic basis.

Treatment of Osteoporosis in Postmenopausal Women and in Men: Recommended Dosage: Orally, 70 mg once a week.
Or, as prescribed by a physician.
Prevention of Postmenopausal Osteoporosis: Recommended Dosage: Orally, 35 mg once a week.
Or, as prescribed by a physician.
Administration Instructions: Take alendronate with plain water only at least 30 minutes before the first food, beverage or medication of the day. Alendronate's absorption will likely be reduced when taken with other beverages (including mineral water), food and some medications. Taking alendronate less than 30 minutes after other medications, food and beverages other than plain water will decrease its absorption and lessen its effect.
Alendronate should only be taken upon arising for the day. It should not be taken at bedtime or before getting up for the day.
Always swallow alendronate with a full glass of water (6 to 8 oz; 180 to 240 mL) to facilitate delivery to the stomach and thus avoid the risk of esophageal irritation.
Do not chew or suck the tablet to avoid oropharyngeal ulceration. Do not lie down within the next 30 minutes and until after the first food of the day.
The patient should follow these instructions to decrease the risk of esophageal adverse events.
Supplemental calcium and vitamin D may be necessary if dietary intake is inadequate. However, patients must wait at least 30 minutes after taking alendronate before taking any other oral medications.
Information on Missed Dose: When a dose is missed, alendronate 70 mg once-weekly tablet should be taken on the morning after the patient remembers. Do not take two doses on the same day. Return to once a week dosing as originally scheduled on the patient's chosen day.

Specific information on acute alendronate overdosage is not available. However, hypocalcemia, hypophosphatemia and upper gastrointestinal adverse events (e.g., upset stomach, heartburn, esophagitis, gastritis, or ulcer) may result from oral overdosage.
Give milk or antacids to bind alendronate. Do not induce vomiting and keep the patient in an upright position to avoid esophageal irritation.
Dialysis is not beneficial and is therefore not recommended.

Hypersensitivity to bisphosphonates or to any component of this product.
Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia.
Inability to stand or sit upright for at least 30 minutes (e.g., bedridden and hospitalized patients).
Renal impairment with creatinine clearance < 35 mL/min.
Hypocalcemia (see General Precautions under Precautions).

Warning on Esophageal and Gastrointestinal Adverse Events: Similar to other bisphosphonate-containing products, local irritation of the upper gastrointestinal mucosa may be expected.
Esophageal adverse events, such as esophagitis, erosions and ulcerations, occasionally with bleeding and rarely followed by esophageal stricture or perforation have been seen in patients receiving alendronate. Some cases were severe and required hospitalization. Patients should be instructed to discontinue alendronate and seek immediate medical attention if symptoms such as dysphagia, odynophagia (pain on swallowing), worsening heartburn, or retrosternal pain develop.
Strictly follow proper administration of the drug to minimize the risk of severe esophageal adverse experience (see Dosage & Administration). Patients who fail to take alendronate properly and/or who continue to take alendronate after developing symptoms suggestive of esophageal irritation have a higher risk of developing severe esophageal reactions (which may be severe and require hospitalization).
Alendronate has possible irritant effects on the upper gastrointestinal mucosa and has a potential for worsening underlying disease. It should therefore be given with caution in patients with active gastrointestinal problems such as dysphagia, esophageal diseases (including Barrett's esophagus), gastritis, duodenitis, ulcers, or with a recent history (within the previous year) of major gastrointestinal diseases such as peptic ulcer, or active gastrointestinal bleeding, or surgery of the upper gastrointestinal tract other than pyloroplasty.
In cases where a patient develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or new or worsening heartburn), they should be instructed to stop taking alendronate immediately and consult their physician.
There have been rare post-marketing reports of gastric and duodenal ulcers, some severe and with complications.
General Precautions: Consider causes of osteoporosis other than estrogen deficiency, aging and glucocorticoid use.
Correct hypocalcemia and other disturbances of mineral metabolism such as vitamin D deficiency before initiating alendronate therapy.
Small, asymptomatic decreases in serum calcium and phosphate may occur, particularly in patients with Paget's disease or patients receiving glucocorticoids.
Osteonecrosis of the Jaw (ONJ): Reports of ONJ have been associated with the use of bisphosphonates including alendronate. ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection (including osteomyelitis) with delayed healing. Although most reports have been in cancer patients treated with intravenous bisphosphonates, some cases have been seen in patients with osteoporosis receiving oral bisphosphonates.
Known risk factors for ONJ include: invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (such as chemotherapy, radiotherapy, corticosteroids, angiogenesis inhibitors, immunosuppressive drugs), poor oral hygiene, co-morbid disorders (such as periodontal and/or other pre-existing dental disease, poorly fitting dentures anemia, coagulopathy, infection, diabetes mellitus), smoking, heavy alcohol use, potency of the bisphosphonate (highest incidence with zoledronic acid), route of administration, and cumulative dose. These patients should consider a dental examination with appropriate preventive dentistry prior to treatment with bisphosphonates. All patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms (e.g, dental mobility, pain, swelling) during bisphosphonate treatment.
For patients requiring invasive dental procedures, the risk for ONJ may be reduced by stopping bisphosphonate treatment. The management plan for each patient should be based on the clinical judgment of the physician and on individual risk/benefit assessment.
Patients who develop ONJ while on bisphosphonate therapy should receive appropriate antibiotic therapy and be seen by an oral surgeon. In these patients, extensive dental surgery may exacerbate the condition. Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment.
Osteonecrosis of the External Auditory Canal: Osteonecrosis of the external auditory canal (cholesteatoma) 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. Consider the possibility of osteonecrosis of the external auditory canal in patients receiving bisphosphonates who present with ear symptoms such as pain or discharge, or chronic ear infections.
Musculoskeletal Pain: Severe and occasionally incapacitating bone, joint and/or muscle pain have been reported infrequently in patients taking bisphosphonates. This may occur from one day to several months after initiation of treatment. Recurrence of symptoms has been observed in some patients when rechallenged with the same medicine or another bisphosphonate. Alendronate therapy may be discontinued if severe symptoms develop.
Atypical Subtrochanteric and Diaphyseal Femoral Fractures: In bisphosphonate-treated patients, atypical, low-energy or low trauma fractures of the femoral shaft have been reported with time to onset in the majority of reports ranging from 18 months to 10 years. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. These fractures also occur in osteoporotic patients who have not been treated with bisphosphonates and therefore the causality of these fractures has not been established.
Atypical femur fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients experience prodromal pain (presenting as dull, aching thigh pain) in the affected area weeks to months before presenting with a completed femoral fracture. Poor healing of these fractures was also reported. Patients with suspected stress fractures should be evaluated, including evaluation for causes and risk factors of stress fractures (e.g., vitamin D deficiency, malabsorption, glucocorticoid use, lower extremity arthritis or fracture, previous stress fracture, extreme or increased exercise, diabetes mellitus, chronic alcohol abuse), and receive appropriate orthopedic care.
Evaluate any patient with a history of bisphosphonate exposure who presents with thigh or groin pain to rule out an incomplete femur fracture. Examine patients with atypical fracture for signs and symptoms of fractures in the contralateral limb. Discontinuation of bisphosphonate therapy should be considered, pending a benefit/risk assessment, on an individual basis.
Endocrine and Metabolism: Mild and transient decreases in serum calcium and phosphate have been observed in patients receiving alendronate, especially in patients with Paget's disease.
Rarely, reports of severe symptomatic hypocalcemia have occurred in patients with predisposing factors such as hypoparathyroidism, vitamin D deficiency and calcium malabsorption. Symptoms of hypocalcemia (e.g., paresthesias or muscle spasms) should be immediately reported to the patient's attending physician. Monitor serum calcium during therapy.
Atrial Fibrillation: A possible increased risk of atrial fibrillation has been observed with the use of bisphosphonates.
Ophthalmic: Conjunctivitis, uveitis, episcleritis and scleritis have been reported with alendronate therapy. Patients should be referred to an ophthalmologist for evaluation in cases where patients experience ocular events other than uncomplicated conjunctivitis. If ocular inflammatory symptoms are observed, treatment may need to be discontinued.
Effects on Ability to Drive and Use Machine (if available): There are no studies performed on the ability of alendronate to affect the ability of a person to drive and/or use machinery. Certain adverse reactions (e.g., dizziness, vertigo, visual disturbances, and severe bone, muscle and joint pain) have been reported which may affect some patients' ability to drive or operate machinery.
Osteogenesis Imperfecta: The overall safety profile of alendronate for 2 years in patients with osteogenesis imperfecta was generally similar to adults. An increased incidence of vomiting, however, was observed in patients with osteogenesis imperfecta compared to those receiving placebo.
Renal Impairment: No dosage adjustment is recommended in patients with mild to moderate kidney impairment (creatinine clearance 35 to 60 mL/minute). Alendronate is contraindicated in patients with severe kidney impairment (creatinine clearance <35 mL/minute).
Use in Children: Alendronate is not indicated for use in pediatric patients.
Use in the Elderly: Dosage adjustment is not necessary in elderly patients. There are no age-related differences in alendronate's efficacy and safety profile. However, some older individuals have greater sensitivity to alendronate.

Pregnancy: Category C.
Alendronate has not been studied in pregnant women. Although no data exist on fetal risk in humans, bisphosphonates are incorporated into the bone matrix and is gradually released over a period of years. This may theoretically cause serious skeletal malformation when a fetus is exposed to alendronate. Alendronate should not be used during pregnancy.
Lactation: It is not known whether alendronate is excreted in human milk. Alendronate should not be used by breastfeeding women.

Alendronate is generally well tolerated and adverse effects are usually mild and do not require discontinuance of the drug. The most frequently reported adverse effects include abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain, and nausea.
Immune system disorders: Hypersensitivity reactions including urticaria and angioedema.
Metabolism and nutrition disorders: Symptomatic hypocalcemia (both in association with predisposing conditions and in patients without known predisposing conditions).
Nervous system disorders: Dizziness, dysgeusia, headache.
Eye disorders: Eye inflammation (uveitis, scleritis or episcleritis).
Ear and labyrinth disorders: Osteonecrosis of the external auditory canal (cholesteatoma), vertigo.
Respiratory, thoracic and mediastinal disorders: Acute asthma exacerbations.
Gastrointestinal disorders: abdominal distention, abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, dysphagia, esophageal erosions, esophageal stricture or perforation, esophageal ulcers, esophagitis, flatulence, gastric or duodenal ulcers (some severe and with complications), gastritis, gastroesophageal reflux disease (GERD), melena, nausea, oropharyngeal ulceration, taste perversion, upper gastrointestinal PUBs (perforation, ulcers, bleeding), vomiting.
Anastomotic ulcer with mild hemorrhage has been reported with concomitant aspirin use.
Esophageal cancer has been reported during postmarketing experience in patients receiving alendronate or other bisphosphonates. The most common site of cancer was the distal esophagus, with gastric involvement in some patients.
Skin and subcutaneous tissue disorders: Alopecia, erythema, pruritus, rash, rash with photosensitivity, severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrosis.
Musculoskeletal and connective tissue disorders: Asthenia, atypical subtrochanteric and diaphyseal femoral fractures, joint swelling, low-energy femoral shaft fracture, malaise, muscle cramp, myalgia; musculoskeletal (bone, muscle or joint) pain occasionally severe and/or incapacitating; osteonecrosis of the jaw generally associated with local infection (including osteomyelitis) and/or tooth extraction with delayed healing.
General disorders and administration site conditions: Fever, peripheral edema; transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically in association with initiation of treatment.
Investigations: Asymptomatic, mild, and transient decreases in serum calcium and phosphate; elevated transaminases.

Calcium Supplements, Antacids and Other Multivalent Cations: Aluminum-, calcium-, iron-, or magnesium-containing compounds such as antacids, mineral supplements, and some osmotic laxatives may interfere with the absorption of alendronate and should therefore be given at least 30 minutes after taking alendronate.
Intravenous Ranitidine: Concomitant administration of intravenous ranitidine doubled the bioavailability of oral alendronate. However, it is not known whether the increased bioavailability has any clinical significance and if this increase in bioavailability will occur in patients who are receiving oral H2-antagonists.
Hormone Replacement Therapy (HRT): The degree of suppression of bone turnover as assessed by mineralizing surface is significantly greater when Hormone Replacement Therapy (HRT) such as estrogen ± progestin is combined with alendronate therapy than with either agent alone in studies of 1 to 2 years duration in postmenopausal women with osteoporosis.
Aspirin: Aspirin should be given with caution in patients receiving alendronate since these drugs may increase the incidence of gastrointestinal or renal adverse events.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Although NSAIDs may be given in patients receiving alendronate, NSAIDs should be given with caution since they may increase the incidence of gastrointestinal adverse events (i.e., gastrointestinal irritation).
Food and Beverages: Food and beverage other than plain water may markedly reduce the absorption and efficacy of alendronate. (See Dosage and Administration.)
Herbal: Take alendronate at least 30 minutes before taking any herbal product since herbal products may interfere with the absorption of alendronate when used concomitantly.
Oral Prednisone: Oral prednisone did not produce a clinically significant change in the oral bioavailability of alendronate (a mean increase ranging from 20-44%) in healthy subjects.

Store at temperatures not exceeding 30°C.

Agents Affecting Bone Metabolism

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

Rx