Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Fosamax Plus D: Alendronate sodium 70 mg and cholecalciferol 2,800 units, Alendronate sodium 70 mg and cholecalciferol 5,600 units
Pharmacology
Mechanism of Action
See individual agents.
Use: Labeled Indications
Osteoporosis: Treatment of osteoporosis in postmenopausal females; treatment to increase bone mass in males with osteoporosis.
Limitations of use: Not for use in the treatment of vitamin D deficiency.
Contraindications
Hypersensitivity to alendronate, vitamin D derivatives, or any component of the formulation; hypocalcemia; abnormalities of the esophagus (eg, stricture or achalasia) which delay esophageal emptying; inability to stand or sit upright for at least 30 minutes
Canadian labeling: Additional contraindications (not in US labeling): Renal insufficiency with CrCl <35 mL/minute
Dosage and Administration
Dosing: Adult
Note: Patients should receive supplemental calcium if dietary intake is inadequate. Some patients may require additional vitamin D while taking this product (not intended to treat vitamin D deficiency).
Osteoporosis, prevention of fractures (males and postmenopausal females): Note: Prior to use, evaluate and treat any potential causes of secondary osteoporosis (eg, hypogonadism in males) (ES [Watts 2012]).
High fracture risk patients, including those with a history of fragility fracture, or males ≥50 years of age and postmenopausal females with a T-score ≤−2.5, or a T-score between −1 and −2.5 at high fracture risk according to an assessment (ES [Eastell 2019]; ES [Watts 2012]; NOF [Cosman 2014]; Siris 2014):
Treatment: Oral: One tablet (alendronate 70 mg/cholecalciferol 2,800 units or alendronate 70 mg/cholecalciferol 5,600 units) once weekly.
Duration of therapy: The optimal duration of therapy has not been established. If fracture risk remains high (eg, fragility fracture before or during therapy) after the initial 5 years, consider extending oral bisphosphonate therapy for up to 10 years (based on data with other bisphosphonates) or switching to alternative therapy (AACE/ACE [Camacho 2016]; Adler 2016; ES [Eastell 2019]; Watts 2010). Alternatively, if bone mineral density (BMD) is stable, there have been no previous fragility fractures, and short-term fracture risk is low, consider discontinuation (ie, drug holiday) after the initial 5 years. The optimal length of a drug holiday has not been established, although it is usually for a period of up to 5 years (ES [Eastell 2019]). The decision to resume therapy after a drug holiday is based on multiple factors, including decline in BMD and risk factors for fracture (AACE/ACE [Camacho 2016]; Adler 2016; ES [Eastell 2019]).
Missed doses: If a once-weekly dose is missed, administer the next morning after remembered. Then return to the original scheduled day of the week on the once-weekly schedule; however, do not administer 2 doses on the same day.
Dosing: Geriatric
Refer to adult dosing.
Administration
Oral: Administer first thing in the morning and ≥30 minutes before the first food, beverage (except plain water), or other medication(s) of the day. Must be taken with 6 to 8 oz of plain water; do not take with mineral water or with other beverages. Swallow whole; do not chew or suck. Patients should be instructed to stay upright (not to lie down) for ≥30 minutes and until after first food of the day (to reduce esophageal irritation).
Dietary Considerations
Ensure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Males and females should consume:
Calcium: 1,000 mg/day (males: 50 to 70 years) or 1,200 mg/day (females ≥51 years and males ≥71 years) (IOM 2011; NOF [Cosman 2014]).
Vitamin D: 800 to 1,000 int. units daily (males and females ≥50 years) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 int. units daily (males and females ≤70 years) or 800 int. units daily (males and females ≥71 years) (IOM 2011).
Wait at least 30 minutes after taking alendronate with cholecalciferol before taking any supplement. Must be taken with at least 6 to 8 oz. plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day. Administer with plain water only; do not administer with mineral-enriched water.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and light. Keep sealed in blister container or original bottle (with desiccant) until use.
Drug Interactions
Aluminum Hydroxide: Vitamin D Analogs may increase the serum concentration of Aluminum Hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Avoid combination
Aminoglycosides: May enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy
Angiogenesis Inhibitors (Systemic): May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Monitor therapy
Aspirin: May enhance the adverse/toxic effect of Alendronate. Specifically, the incidence of upper gastrointestinal adverse events may be increased Monitor therapy
Bile Acid Sequestrants: May decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification
Cardiac Glycosides: Vitamin D Analogs may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy
Danazol: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy
Deferasirox: Bisphosphonate Derivatives may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Consider therapy modification
Mineral Oil: May decrease the serum concentration of Vitamin D Analogs. More specifically, mineral oil may interfere with the absorption of Vitamin D Analogs. Management: Avoid concomitant, oral administration of mineral oil and vitamin D analogs. Consider separating the administration of these agents by several hours to minimize the risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification
Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Monitor therapy
Orlistat: May decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Consider therapy modification
Parathyroid Hormone: Alendronate may diminish the therapeutic effect of Parathyroid Hormone. More specifically, Alendronate may interfere with normalization of blood calcium concentrations. Avoid combination
Polyvalent Cation Containing Products: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral medications containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Proton Pump Inhibitors: May diminish the therapeutic effect of Bisphosphonate Derivatives. Monitor therapy
Sucralfate: Vitamin D Analogs may increase the serum concentration of Sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Avoid combination
Thiazide and Thiazide-Like Diuretics: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy
Vitamin D Analogs: May enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combination
Test Interactions
Bisphosphonates may interfere with diagnostic imaging agents such as technetium-99m-diphosphonate in bone scans.
Adverse Reactions
See individual agents.
Warnings/Precautions
Concerns related to adverse effects:
- Bone fractures: Atypical femur fractures (AFF) have been reported in patients receiving bisphosphonates. The fractures include subtrochanteric femur (bone just below the hip joint) and diaphyseal femur (long segment of the thigh bone). Some patients experience prodromal pain weeks or months before the fracture occurs. It is unclear if bisphosphonate therapy is the cause for these fractures; AFFs have also been reported in patients not taking bisphosphonates, and in patients receiving glucocorticoids. Patients receiving long-term (>3 to 5 years) bisphosphonate therapy may be at an increased risk (Adler 2016; NOF [Cosman 2014]); however, benefits of therapy (when used for osteoporosis) generally outweigh absolute risk of AFF within the first 5 years of treatment, especially in patients with high fracture risk (Adler 2016; ES [Eastell 2019]). Patients presenting with thigh or groin pain with a history of receiving bisphosphonates should be evaluated for femur fracture. Consider interrupting bisphosphonate therapy in patients who develop a femoral shaft fracture; assess for fracture in the contralateral limb.
- Bone/joint/muscle pain: Severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Consider discontinuing therapy in patients who experience severe symptoms; symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with the same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy.
- GI mucosa irritation: May cause irritation to upper GI mucosa. Esophagitis, dysphagia, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Discontinue use if new or worsening symptoms develop.
- Ocular effects: Conjunctivitis, uveitis, episcleritis, and scleritis have been reported with alendronate; patients presenting with signs of ocular inflammation may require further ophthalmologic evaluation.
- Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients receiving bisphosphonates. Known risk factors for MRONJ include invasive dental procedures (eg, tooth extraction, dental implants, boney surgery), cancer diagnosis, concomitant therapy (eg, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, ill-fitting dentures, and comorbid disorders (anemia, coagulopathy, infection, preexisting dental or periodontal disease). Risk may increase with increased duration of bisphosphonate use. According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonates and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy; risk of MRONJ is significantly higher in cancer patients receiving antiresorptive therapy compared to patients receiving osteoporosis treatment (regardless of medication used or dosing schedule). MRONJ risk is also increased with intravenous antiresorptive use compared with the minimal risk associated with oral bisphosphonate use, although risk appears to increase with oral bisphosphonates when duration of therapy exceeds 4 years (AAOMS [Ruggiero 2014]). The manufacturer’s labeling states that in patients requiring invasive dental procedures, discontinuing bisphosphonates may reduce the risk of ONJ, and clinical judgment should guide the decision. However, the AAOMS suggests there is currently no evidence that interrupting oral bisphosphonate therapy alters the risk of ONJ following tooth extraction, and that in patients receiving oral bisphosphonates for <4 years who have no clinical risk factors, no alternations or delay in any procedure common to oral/maxillofacial surgeons, periodontists, and other dental providers is necessary (special considerations apply to patients receiving dental implants). Conversely, in patients receiving oral bisphosphonates for >4 years or in patients receiving oral bisphosphonates for <4 years who have also taken corticosteroids or antiangiogenic medications concomitantly, the AAOMS recommends considering a 2-month, drug-free period prior to invasive dental procedures (recommendation based on a theoretical benefit). Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]). According to the manufacturer, discontinuation of the bisphosphonate therapy should be considered (based on risk/benefit evaluation) in patients who develop ONJ.
Disease-related concerns:
- Bariatric surgery: Altered absorption and ulceration risk: Avoid oral bisphosphates after bariatric surgery; inadequate oral absorption and potential anastomotic ulceration may occur. If therapy is indicated, IV administered bisphosphonates are recommended.
- GI malabsorption syndrome: Increased doses of vitamin D supplementation may be required in patients with GI malabsorption syndrome; consider monitoring 25-hydroxy vitamin D levels.
- Hypercalcemia: May exacerbate hypercalcemia and/or hypercalciuria in certain disease states (eg, leukemia, lymphoma, sarcoidosis); monitor serum and urine calcium levels.
- Hypocalcemia/vitamin D deficiency: Before therapy initiation hypocalcemia and/or vitamin D deficiency must be corrected; ensure adequate calcium and vitamin D intake. Do not use to treat vitamin D deficiency.
- Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with CrCl <35 mL/minute).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Monitoring Parameters
Serial bone mineral density (BMD) should be evaluated at baseline and every 1 to 3 years on treatment (usually at ~2 years following initiation of therapy, then more or less frequently depending on patient-specific factors and stability of BMD) (AACE/ACE [Camacho 2016]; ES [Eastell 2019]; NOF [Cosman 2014]); evaluate BMD every 2 to 4 years during a drug holiday (ES [Eastell 2019]); annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; may consider monitoring biochemical markers of bone turnover (eg, fasting serum CTX or urinary NTX) at baseline, 3 months, and 6 months, to assess treatment response, adherence to therapy, and/or possible malabsorption (ES [Eastell 2019]).
Pregnancy
Pregnancy Considerations
Refer to individual monographs.
Patient Education
What is this drug used for?
- It is used to treat soft, brittle bones (osteoporosis).
Frequently reported side effects of this drug
- Abdominal pain
- Constipation
- Nausea
- Vomiting
- Diarrhea
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Low calcium like muscle cramps or spasms, numbness and tingling, or seizures
- Black, tarry, or bloody stools
- Chest pain
- Coughing up blood
- Heartburn
- Trouble swallowing
- Severe pain when swallowing
- Sore throat
- Vomiting blood
- Severe bone pain
- Severe joint pain
- Severe muscle pain
- Groin, hip, or thigh pain
- Mouth sores
- Jaw pain or swelling
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
