Alendronate and cholecalciferol

U.S. BRAND NAMES — Fosamax Plus D™
PHARMACOLOGIC CATEGORY Bisphosphonate DerivativeVitamin D Analog
DOSING: ADULTS — Osteoporosis: Oral: One tablet once weekly
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Clcr <35 mL/minute: Not recommended
DOSING: HEPATIC IMPAIRMENT — Alendronate: None necessary. Cholecalciferol: May not be adequately absorbed in patients who have malabsorption due to inadequate bile production.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
DOSAGE FORMS: CONCISE Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (6-8 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Patient should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation).
USE — Treatment of osteoporosis in postmenopausal females; increase bone mass in males with osteoporosis
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, vitamin D derivatives, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; malabsorption syndrome; evidence of vitamin D toxicity
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, 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. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, 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). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis. However, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: 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. Hypercalcemia: May exacerbate hypercalcemia in certain disease states (eg, leukemia, lymphoma, sarcoidosis); monitor serum calcium levels. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS — See individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. No animal data are available for the use of cholecalciferol in pregnancy; however, high-dose ergocalciferol has demonstrated abortifacient properties and aortic abnormalities in rabbits. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Cholecalciferol enters breast milk; excretion of alendronate in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake. May require additional vitamin D supplementation, particularly in patients at risk for vitamin D deficiency (eg, malabsorption syndromes, chronically ill, >70 years of age). Wait at least 30 minutes after taking alendronate with cholecalciferol before taking any supplement. Must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Tablets (Fosamax Plus D) 70-2800 MG-UNIT (4): $79.70
MONITORING PARAMETERS — Alkaline phosphatase (measured periodically); urine and serum calcium, serum phosphorus, serum 25-hydroxy vitamin D; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging
Phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
25-hydroxyvitamin D: 10-80 ng/mL (higher during summer)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms may include anorexia, polyuria, polydipsia, lethargy, hypo-/hypercalcemia, hypophosphatemia, and upper GI adverse effects (eg, upset stomach, heartburn, esophagitis, gastritis, or ulcer). Treat with milk or antacids to bind alendronate. Hydration, systemic glucocorticoids, and reduction of calcium intake may be beneficial in correcting hypercalcemia. Dialysis would not be beneficial.
CANADIAN BRAND NAMES — Fosavance
INTERNATIONAL BRAND NAMES — Fosamax Plus (AR, HK, MX); Fosavance (AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PH, PT, RU, SE, TR); Maximus (PE)
MECHANISM OF ACTION — See individual agents.
PATIENT INFORMATION — Do not take more than the recommended amount. While taking this medication, your prescriber may want you to follow a special diet or take a calcium supplement. Follow this diet closely. Avoid taking magnesium supplements or magnesium-containing antacids. Early symptoms of hypercalcemia include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, cramps, diarrhea, muscle pain, bone pain, and irritability.
(For additional information see "Alendronate and cholecalciferol: Patient drug information")