Reventa

Alendronic acid (as alendronate sodium trihydrate).

Reventa is an aminobisphosphonate that acts as a potent inhibitor of bone resorption.
Alendronic acid is (4-amino-1-hydroxybutylidene) bisphosphonic acid monosodium salt trihydrate. Its molecular formula is C₁₄H₁₂NNaO₇P₂·3H₂O.

Pharmacology: Mechanism of Action: At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclast recruitment or attachment but it does inhibit osteoclast activity. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces.
Pharmacokinetics: Absorption: Like other bisphosphonates, alendronate is poorly absorbed following oral administration. Absorption is decreased by food especially by products containing calcium or other polyvalent cations. Bioavailability is about 0.4% when administered ½ hr before food, reduced from 0.7% in the fasting state; absorption is negligible when taken up to 2 hrs after a meal.
Distribution: The mean steady-state volume of distribution, exclusive of the bone, is at least 28 L in humans. Concentrations of the drug in plasma following therapeutic oral doses are too low (<5 ng/mL) for analytical detection. Protein-binding in human plasma is approximately 78%.
Metabolism: There is no evidence that alendronate is metabolized in animals or humans.
Elimination: About ½ of the absorbed portion is excreted in the urine; the remainder is sequestered to bone for a prolonged period. The terminal t_½ in humans is estimated to exceed 10 years, probably reflecting release of alendronate from the skeleton.
Special Populations: Pediatric: Alendronate pharmacokinetics have not been studied in patients <18 years.
Geriatric: Bioavailability and urinary excretion are similar in elderly (>60 years) and younger subjects. No dosage adjustment is necessary.
Renal Insufficiency: No dosage adjustment is necessary for patients with mild to moderate renal insufficiency (creatinine clearance 35-60 mL/min). Alendronate is not recommended in patients with severe renal impairment.
Hepatic Insufficiency: As there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic insufficiency. No dosage adjustment is necessary.
Drug-Drug Relationship: Ranitidine: Intravenous ranitidine was shown to double the bioavailability of oral alendronate. The clinical significance of this increased bioavailability and whether similar increase will occur in patients given oral H₂-antagonists is unknown.
Prednisone: Prednisone (20 mg 3 times daily for 5 days) did not produce a clinically meaningful change in the oral bioavailability of alendronate (mean increase ranging from 20-44%).

Treatment of osteoporosis in postmenopausal women and men to prevent fractures, including those of the hip and spine (vertebral compression fractures).

Treatment of Osteoporosis in Postmenopausal Women and Men: Recommended Dose: 70 mg once weekly.
Administration: Food and drinks affect the absorption of alendronic acid. Therefore, it is very important that alendronic acid must not be used with food or drinks (other than water). The tablets must be swallowed whole, with a full glass of water and not chewed. Patients should not lie down for 30 min after taking Reventa. Reventa should not be taken at bedtime.

No specific information is available on the treatment of overdosage with alendronate. Hypocalcemia, hypophosphatemia and upper gastrointestinal adverse events eg, upset stomach, heartburn, esophagitis, gastritis or ulcer may result from oral overdosage. Milk or antacids should be given to bind alendronate. Due to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

Hypersensitivity to any components of Reventa.
Abnormalities of the esophagus which delay esophageal emptying eg, stricture or achalasis.
Inability to stand or sit upright for at least 30 min.
Hypocalcemia.

General: Causes of osteoporosis other than estrogen deficiency, aging and glucocorticoid use should be considered.
Hypocalcemia must be corrected before initiating therapy with alendronate.
Other disorders affecting mineral metabolism (eg, vitamin D deficiency) should also be treated. Patients with these conditions, serum calcium and symptoms of hypocalcemia should be monitored during therapy.
Ensuring adequate calcium absorption and vitamin D intake is especially important in patients with Paget's disease of bone and in patients receiving glucocorticoids, as small asymptomatic decreases in serum calcium and phosphate may occur with alendronate treatment.
Gastrointestinal: Physicians should be alert to symptoms signalling a possible esophageal reaction including dyaphasis, odynophagia, retrosternal pain or new/worsening heartburn. Patients should be instructed to discontinue alendronate.
Because of possible irritant effects of alendronate on the upper gastrointestinal mucosa and a potential for worsening of the underlying disease, caution should be used when alendronate is given to patients with active upper gastrointestinal problems.
Renal Insufficiency: Alendronate is not recommended for patients with severe renal insufficiency (creatinine clearance <35 mL/min) due to lack of experience in renal failure.
Glucocorticoid-induced Osteoporosis: The risk versus benefit of alendronate for treatment at daily dosages of glucocorticoids <7.5 mg of prednisone or equivalent has not been established. Before initiating treatment, the hormonal status of both men and women should be ascertained and appropriate replacement considered. A bone mineral density measurement should be made at the initiation of therapy and repeated after 6-12 months of combined alendronate and glucocorticoid treatment.
Use in pregnancy: There are no studies in pregnant women. Alendronate should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
Use in lactation: It is not known whether alendronate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when alendronate is administered to nursing women.
Use in children: Safety and effectiveness in pediatric patients have not been established.

Use in pregnancy: There are no studies in pregnant women. Alendronate should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
Use in lactation: It is not known whether alendronate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when alendronate is administered to nursing women.

The adverse reactions experienced were usually mild and generally did not require discontinuation of therapy. The following adverse reactions have been reported.
Body as a Whole: Common: Hypersensitivity reactions including urticaria, transient symptoms of myalgia and malaise. Rare: Angioedema, fever, symptomatic hypocalcemia.
Gastrointestinal: Common: Esophagitis, esophageal erosions and ulcers. Rare: Esophageal stricture or perforation and oropharyngeal ulceration.
Gastric or duodenal ulcers, some severe and with complications have also been reported.
Skin: Common: Rash (occassionally with photosensitivity), pruritis. Rare: Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Special Senses: Rare: Uveitis, scleritia.

Estrogen/Hormone Replacement Therapy (HRT): Combined use of alendronate and HRT resulted in greater increases in bone mass, together with greater decreases in bone turnover, than seen with either treatment alone. The safety and tolerability profile of the combination was consistent with those of the individual treatments.
Calcium Supplements/Antacids: It is likely that calcium supplements, antacids and some oral medications will interfere with absorption of alendronate. Therefore, patients must wait at least ½ hr after taking alendronate before taking any other oral medications.
Aspirin: The incidence of upper gastrointestinal adverse events increased in patients receiving concomitant therapy with daily doses of alendronate >10 mg and aspirin-containing products.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Since NSAID use is associated with gastrointestinal irritation, caution should be used during concomitant use with alendronate.

Store at temperatures not exceeding 30°C. Protect from sunlight and moisture.

Agents Affecting Bone Metabolism

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

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