Fosamax

Oral Bisphosphonates

Administer after the patient has risen for the day. The patient should be sitting or standing. Do not administer alendronate to the patient while the patient is lying down.
Administer with plain water only and at least 30 minutes before the first food, beverage, or other medications of the day. At least 30 minutes should elapse after an alendronate dose before taking any other drugs.
To avoid esophageal irritation, the patient should not lie down for at least 30 minutes after the dose and until after their first food of the day. Do not administer at bedtime or before the patient has risen for the day.
Missed dose of a daily regimen: Instruct the patient not to take a dose later in the day. Instruct the patient to skip the missed dose and to return to the usual schedule the next morning. They should not take 2 doses on the same day.
Missed doses of a once-weekly dose regimen: If a once-weekly dose is missed, instruct the patient to take the dose on the morning after they remember. They should not take 2 doses on the same day but should return to taking 1 dose once a week, as originally scheduled on their chosen day.[28644] [52249]
Ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia.

Tablets:
Administer in the morning with a full glass of plain water (180 to 240 mL or 6 to 8 ounces).

Oral Solution:
Use an oral syringe or other calibrated device for accurate dosage.
Administer in the morning with at least 60 mL (2 ounces) of water.[28644]
 
Effervescent tablets for oral solution:
Do not have patient swallow the undissolved effervescent tablet; do not chew or allow the tablet to dissolve in the mouth due to the risk of oropharyngeal irritation.
Dissolve 1 tablet in 120 mL (4 ounces) of plain, unflavored, room temperature water only.
After completion of the effervescence, wait at least 5 minutes and then stir the solution for approximately 10 seconds and have the patient ingest.[52249]

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

NOTE: Alendronate is not approved by the FDA for intravenous administration. An intravenous product is not available in the U.S.
Dilute dose in 250 mL or 500 mL 0.9% Sodium Chloride Injection.
Do not mix with any other drug products.
An IV infusion time of 2 to 6 hours has been recommended.

esophageal ulceration / Delayed / 0.1-1.5
peptic ulcer / Delayed / 0-1.1
atrial fibrillation / Early / Incidence not known
GI perforation / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
esophageal stricture / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
uveitis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
osteonecrosis / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known

hypocalcemia / Delayed / 18.0-18.0
hypophosphatemia / Delayed / 10.0-10.0
constipation / Delayed / 0-3.1
melena / Delayed / 0-1.3
gastritis / Delayed / 0.2-1.1
dysphagia / Delayed / 0.1-1.0
oral ulceration / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
lymphopenia / Delayed / Incidence not known
bone pain / Delayed / Incidence not known
erythema / Early / Incidence not known
ocular inflammation / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known

abdominal pain / Early / 0.9-6.6
musculoskeletal pain / Early / 0.4-6.0
flatulence / Early / 0-4.1
nausea / Early / 0-3.6
dyspepsia / Early / 1.1-3.6
diarrhea / Early / 0-3.1
gastroesophageal reflux / Delayed / 0.7-2.8
headache / Early / 0-2.6
muscle cramps / Delayed / 0-1.1
vomiting / Early / 0.2-1.0
dysgeusia / Early / 0.1-0.5
pyrosis (heartburn) / Early / Incidence not known
asthenia / Delayed / Incidence not known
vertigo / Early / Incidence not known
dizziness / Early / Incidence not known
malaise / Early / Incidence not known
fever / Early / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
urticaria / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
rash / Early / Incidence not known
ocular pain / Early / Incidence not known

Binosto, Fosamax

Rx

Oral second-generation bisphosphonate; weekly or daily regimens available for selected conditions
Used primarily for treatment and prevention of osteoporosis in both men and postmenopausal women; also indicated for corticosteroid-induced osteoporosis
Also used for adults with Paget's disease

10 mg PO once daily. Supplement calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Continue an oral bisphosphonate for up to 10 years in postmenopausal women who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk postmenopausal women. For those patients at low or moderate risk for fracture, consider stopping alendronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Bisphosphonates are first-line therapy for the treatment of osteoporosis in postmenopausal women; the drug is additionally effective in men with osteoporosis.[62806]

70 mg PO once weekly. Supplement calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Continue an oral bisphosphonate for up to 10 years in postmenopausal women who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk postmenopausal women. For those patients at low or moderate risk for fracture, consider stopping alendronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Bisphosphonates are first-line therapy for the treatment of osteoporosis in postmenopausal women; the drug is additionally effective in men with osteoporosis.[62806]

5 mg PO once daily. For postmenopausal women who are not taking estrogen hormonal replacement, the dose is 10 mg PO daily. Supplement calcium and vitamin D if dietary intake is inadequate. For use in patients taking systemic corticosteroids (i.e., equivalent to prednisone 7.5 mg/day PO or more). The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping alendronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.

35 mg PO once weekly. Supplement calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping alendronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Use of bisphosphonates to prevent bone loss can be considered in postmenopausal women with low bone mineral density (T-score less than -1) and other risk factors for fracture who do not meet criteria for osteoporosis treatment.

5 mg PO once daily. Supplement calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping alendronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Use of bisphosphonates to prevent bone loss can be considered in postmenopausal women with low bone mineral density (T-score less than -1) and other risk factors for fracture who do not meet criteria for osteoporosis treatment.

5 mg PO once daily. For postmenopausal women who are not taking estrogen hormonal replacement, the dose is 10 mg PO daily. Supplement calcium and vitamin D if dietary intake is inadequate. For use in patients taking systemic corticosteroids (i.e., equivalent to prednisone 7.5 mg/day PO or more). The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping alendronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.

40 mg PO once daily for 6 months. Supplement calcium and vitamin D if dietary intake is inadequate. Retreatment may be considered after a 6-month post-treatment evaluation period, based on increases in serum alkaline phosphatase.[28644] Alendronate is associated with histologic and radiologic evidence of disease improvement, but guidelines suggest that retreatment with alendronate may be necessary within 2 to 6 years. Guidelines also recommend a single dose of zoledronic acid preferentially due to the rare need for retreatment within 5 years, but the alendronate regimen is also an acceptable option. There are long-term data for reducing pain and lytic lesions and improving quality of life.[63474]

Safety and efficacy have not been established. This dosage form is not available in the U.S. Doses of 5 mg, 7.5 mg, or 10 mg of alendronate IV infusion over 2 to 6 hours appear to be effective. While doses of 12.5 and 15 mg have also been studied, they may not provide any significant benefit over lower doses in terms of achieving serum calcium reduction.

10 mg PO once daily.

10 mg PO once daily.

5 to 10 mg PO once daily.

5 mg PO once daily.

70 mg PO once weekly.

70 mg PO once weekly.

40 mg PO once daily for 8 weeks.

†Indicates off-label use

No dosage adjustment is needed.

CrCl 35 mL/minute or more: No dosage adjustment is needed.
CrCl less than 35 mL/minute: Not recommended.

Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aluminum Hydroxide: (Moderate) Separate administration of alendronate and aluminum hydroxide by at least 30 minutes. Aluminum-containing antacids will interfere with the absorption of alendronate.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of alendronate and aluminum hydroxide by at least 30 minutes. Aluminum-containing antacids will interfere with the absorption of alendronate.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate administration of alendronate and aluminum hydroxide by at least 30 minutes. Aluminum-containing antacids will interfere with the absorption of alendronate.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of alendronate and aluminum hydroxide by at least 30 minutes. Aluminum-containing antacids will interfere with the absorption of alendronate.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of alendronate and aluminum hydroxide by at least 30 minutes. Aluminum-containing antacids will interfere with the absorption of alendronate.
Aspirin, ASA: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product. (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Dipyridamole: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Omeprazole: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Oxycodone: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Bumetanide: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Calcium (oral): (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including alendronate.
Ethacrynic Acid: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Food: (Major) Absorption of alendronate is very poor; oral bioavailability is less than 1%. Because of this, food interactions can be very significant. Alendronate oral absorption becomes almost negligible if alendronate is taken within 2 hours of breakfast. Even orange juice or coffee can reduce bioavailability by about 60%. To achieve maximum possible bioavailability alendronate must be taken in the fasting state and at least 2 hours before a standard breakfast.
Furosemide: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Separate administration of alendronate and iron supplements by at least 30 minutes. Iron will interfere with the absorption of alendronate.
Iron: (Moderate) Separate administration of alendronate and iron supplements by at least 30 minutes. Iron will interfere with the absorption of alendronate.
Lanthanum Carbonate: (Moderate) To limit absorption problems, the oral bisphosphonates should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like the oral bisphosphonates, may also be bound by lanthanum carbonate. Separating times of administration will maximize absorption and clinical benefit of the bisphosphonate. Separate the times of administration appropriately. Monitor the patient's clinical status and bone density as recommended to ensure the appropriate response to bisphosphonate therapy is obtained.
Levothyroxine: (Moderate) Separating times of administration of alendronate from levothyroxine and other medications will maximize alendronate absorption and clinical benefit. For example, administering the levothyroxine dose at bedtime can avoid this interaction with alendronate. The bioavailability of alendronate was slightly decreased when alendronate and levothyroxine were co-administered to healthy subjects The mean AUC and Cmax of alendronate decreased by 7% and 9%, respectively. Alendronate should always be administered upon arising for the day and at least 30 minutes before the first food, beverage, or other medication of the day. To minimize interactions, levothyroxine is also best taken on an empty stomach with a glass of water.
Levothyroxine; Liothyronine (Porcine): (Moderate) Separating times of administration of alendronate from levothyroxine and other medications will maximize alendronate absorption and clinical benefit. For example, administering the levothyroxine dose at bedtime can avoid this interaction with alendronate. The bioavailability of alendronate was slightly decreased when alendronate and levothyroxine were co-administered to healthy subjects The mean AUC and Cmax of alendronate decreased by 7% and 9%, respectively. Alendronate should always be administered upon arising for the day and at least 30 minutes before the first food, beverage, or other medication of the day. To minimize interactions, levothyroxine is also best taken on an empty stomach with a glass of water.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Separating times of administration of alendronate from levothyroxine and other medications will maximize alendronate absorption and clinical benefit. For example, administering the levothyroxine dose at bedtime can avoid this interaction with alendronate. The bioavailability of alendronate was slightly decreased when alendronate and levothyroxine were co-administered to healthy subjects The mean AUC and Cmax of alendronate decreased by 7% and 9%, respectively. Alendronate should always be administered upon arising for the day and at least 30 minutes before the first food, beverage, or other medication of the day. To minimize interactions, levothyroxine is also best taken on an empty stomach with a glass of water.
Loop diuretics: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Magnesium Citrate: (Moderate) Separate administration of alendronate and magnesium-containing supplements by at least 30 minutes. Magnesium will interfere with the absorption of alendronate.
Magnesium Salts: (Moderate) Separate administration of alendronate and magnesium-containing supplements by at least 30 minutes. Magnesium will interfere with the absorption of alendronate.
Magnesium: (Moderate) Separate administration of alendronate and magnesium-containing supplements by at least 30 minutes. Magnesium will interfere with the absorption of alendronate.
Nonsteroidal antiinflammatory drugs: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Omeprazole; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Parathyroid Hormone: (Moderate) Coadministration of alendronate with parathyroid hormone (PTH) is not recommended as concomitant use leads to a reduction in the calcium sparing effect, which can interfere with the normalization of serum calcium. The use of PTH alone was superior to use in combination with alendronate in clinical trials. In clinical trials, there was no evidence of synergy between PTH and alendronate. Changes in the volumetric density of trabecular bone, the cortical volume at the hip, and levels of markers of bone turnover suggest that the concurrent use of alendronate may reduce the anabolic effects of PTH. Concurrent use with other bisphosphonates is also controversial. However, sequential use (e.g., PTH followed by anti-resorptive treatment with bisphosphonates) appears to be beneficial and to help maintain beneficial bone effects.
Polycarbophil: (Moderate) Coadministration of alendronate with calcium polycarbophil can interfere with the oral absorption of alendronate; do not administer calcium polycarbophil within 30 minutes of alendronate. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
Proton pump inhibitors: (Moderate) Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.
Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Separate administration of alendronate and magnesium-containing supplements by at least 30 minutes. Magnesium will interfere with the absorption of alendronate.
Sucralfate: (Moderate) Concomitant administration of oral alendronate with aluminum-containing medications (e.g., sucralfate) may interfere with the absorption of alendronate. Separation of administration is advised. At least 30 minutes should elapse after an alendronate dose before taking aluminum-containing drugs.
Torsemide: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.

Alendronate Sodium/Alendronic Acid/Fosamax Oral Sol: 70mg, 75mL
Alendronate Sodium/Alendronic Acid/Fosamax Oral Tab: 5mg, 10mg, 35mg, 70mg
Binosto Oral Tab Effrv: 70mg

10 mg/day PO or 70 mg/week PO for osteoporosis. For Paget's disease 40 mg/day PO for 6 months.

10 mg/day PO or 70 mg/week PO for osteoporosis. For Paget's disease 40 mg/day PO for 6 months.

Weighing 30 kg or more: Safety and efficacy have not been established; however, 10 mg/day PO has been used off-label for osteogenesis imperfecta.
Weighing less than 30 kg: Safety and efficacy have not been established; however, 5 mg/day PO has been used off-label for osteogenesis imperfecta.

3 to 12 years weighing 30 kg or more: Safety and efficacy have not been established; however, 10 mg/day PO has been used off-label for osteogenesis imperfecta.
3 to 12 years weighing less than 30 kg: Safety and efficacy have not been established; however, 5 mg/day PO has been used off-label for osteogenesis imperfecta.
1 to 2 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Alendronate is a second-generation bisphosphonate that binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts, the bone-resorbing cells. Alendronate reduces bone resorption with no direct effect on bone formation, although the latter process is ultimately reduced because bone resorption and formation are coupled during bone turnover. 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. Studies in mice on the localization of radioactive alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined 6 and 49 days after radioactive alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass. [52249] [26651] [50514]
 
Like other bisphosphonates, the exact mechanism of alendronate's therapeutic effect in patients with Paget's disease has not been established. Paget's disease is a progressive, idiopathic disease of bone. Increasing numbers of unusually large osteoclasts are produced at affected sites. Increased osteoclastic bone resorption follows, which is compensated for by an increase in osteoblastic bone formation, leading to the replacement of the normal bone architecture by disorganized, enlarged, and weakened bone structure. This new bone architecture is inferior and often deformed, and can fracture easily. Bisphosphonates are believed to reduce the solubility of the mineralized bone matrix by adsorption to hydroxyapatite crystals in the matrix. The matrix becomes less soluble and resistant to osteoclastic resorption, which helps stabilize osteolytic lesions. Alendronate and other bisphosphonates can also block the formation of mature osteoclasts by affecting the attachment of osteoclast precursors to the mineralized matrix. In patients with Paget's disease, alendronate directly decreases bone resorption, resulting in a significant decrease in serum alkaline phosphatase and urinary markers of bone collagen degradation. Bisphosphonates cause histological and radiological evidence of Paget's disease improvement and also reduce pain.[28644] [24426] [50514]
 
Some bisphosphonates cause a significant decrease in serum calcium and urinary calcium levels in patients with hypercalcemia of malignancy, and some bisphosphonate agents in selected cancer patients may reduce osteopenia related to cancer treatment and thus help reduce skeletal events.[24428] [24429] [50514]

Alendronate is administered orally. Transient distribution into soft tissue is rapidly followed by redistribution to bone or urinary excretion. Alendronate is approximately 78% bound to protein in human plasma. There is no evidence that any metabolism takes place.  Once alendronate is bound to bone, the half-life is more than 10 years. Inhibition of bone resorption diminishes after completion of treatment, suggesting that not all the alendronate sequestered in bone is biologically active. 
Bone resorption in individual remodeling units normally continues for approximately 2 weeks. Due to the long half-life of alendronate in the bone, weekly administration of alendronate should inhibit bone resorption and provide benefits on bone mass and strength to a similar extent as daily administration.

Absorption of alendronate is poor, with oral bioavailability of less than 1%.  Cations (e.g., calcium, magnesium) reduce bioavailability. If alendronate is taken within 2 hours of breakfast its bioavailability becomes almost negligible. Even orange juice or coffee can reduce bioavailability by about 60%. To achieve maximum possible bioavailability, alendronate must be taken in the fasting state and at least 2 hours before a standard breakfast. Estimations suggest that the amount of alendronate released from the skeleton daily, after 10 years of daily dosing with 10 mg of alendronate, is 25% of that absorbed from the GI tract.

Elimination of alendronate from plasma is rapid, falling 95% within 6 hours of an IV dose. Approximately 50% of a single IV dose is excreted in the urine within 72 hours. 

There are no studies of alendronate use during pregnancy. It is prudent to avoid alendronate use during pregnancy unless the potential benefit to the mother justifies any possible risk to the fetus.[28644] [52249] Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the dose and duration of bisphosphonate use. There are no data on fetal risk in humans. However, there is a theoretical risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. Bisphosphonates do cause fetal harm (predominantly skeletal) in animals, suggesting the uptake of bisphosphonates into fetal bone is greater than into maternal bone. Animal reproductive studies indicate alendronate may induce fetal skeletal changes, a decrease in maternal serum calcium and protracted parturition, as well as a possible effect on fetal viability.[28644] [52249]

Alendronate should be used with caution during breast-feeding.[28644] [52249] It is not known if alendronate is excreted into human milk. The effects of alendronate on a breastfed infant are not known. Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount available for release back into the systemic circulation for potential excretion into breast milk, is directly related to the dose and duration of bisphosphonate use.[28644] [52249] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.