Fosamax Plus D (alendronate sodium/cholecalciferol (vitamin D3))

Dietary intake of ergocalciferol and cholecalciferol varies among individual patients, and dietary intake should always be considered when calculating the appropriate dosage of vitamin D analogs. During therapy with vitamin D analogs, dosage depends on the nature and severity of the patient's hypocalcemia and must be individualized to maintain serum calcium concentrations of 9-10 mg/dL. In the management of hypoparathyroidism, pseudohypoparathyroidism, and familial hypophosphatemia, the range between therapeutic and toxic effects is narrow; however, hypercalcemia may occur at any time when therapeutic doses of vitamin D analogs are used, and careful monitoring is imperative. In the management of secondary hyperparathyroidism, dosage of vitamin D analogs should be individualized according to serum or plasma intact parathyroid hormone (iPTH) concentrations and serum calcium and phosphorus concentrations.

During therapy with vitamin D analogs, patients should receive adequate amounts of calcium through management of diet or administration of calcium supplements; however, overdosage of calcium may lead to hypercalcemia. Dosage of vitamin D analogs should be decreased when symptoms improve and before biochemical normality or complete bone healing has occurred because requirements for vitamin D analogs often decrease after bone healing occurs. In patients who become bedridden (especially children), dosage reduction may occasionally be needed to avoid hypercalcemia.

Dosage of alendronate sodium, which is present as the monosodium trihydrate, is expressed in terms of alendronate.

Vitamin D analogs are usually administered orally; however, calcitriol, doxercalciferol, and paricalcitol may be given by IV injection. Ergocalciferol may be given by IM injection; however, a suitable formulation of the drug for IM injection no longer is commercially available in the US.

Alendronate sodium is administered orally as tablets or oral solution. The drug should be taken only upon rising for the day. Alendronate tablets and oral solution have equivalent bioavailability.

The fixed combination of alendronate sodium and cholecalciferol is administered orally as tablets.

To facilitate absorption of alendronate (alone or in fixed combination with cholecalciferol), the drug should be taken with a full glass (180-240 mL) of plain water at least 30 minutes before the first food, beverage, or other orally administered drug of the day; waiting longer than 30 minutes before eating, drinking, or ingesting another drug will improve absorption of alendronate. To facilitate gastric emptying when alendronate oral solution is given, the patient should drink at least 60 mL (2 ounces, 1/4 cup) of water following administration of the drug. Because of the potential for oropharyngeal irritation or ulceration, patients should be instructed not to suck or chew alendronate tablets. Alendronate (alone or in combination with cholecalciferol) should be administered in an upright position (sitting or standing). Patients should be instructed to avoid lying down for at least 30 minutes following administration and until after the first food of the day to facilitate delivery of the drug to the stomach and minimize potential esophageal irritation. (See Upper GI Effects under Cautions: Warning/Precautions.) In addition, patients should be instructed not to take alendronate (alone or in fixed combination with cholecalciferol) at bedtime or before arising for the day.

If a patient misses a weekly dose of alendronate or alendronate/cholecalciferol, the missed dose should be taken the morning after it is remembered, followed by resumption of the regular weekly schedule. Patients should not take 2 tablets on the same day.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Serum Phosphate Level-Altering Drugs/Erdafitinib

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1)

CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1)

DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Fat Soluble Vitamins/Colesevelam

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

CLINICAL EFFECTS: Colesevelam may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by colesevelam should be borne in mind during implementation of a vitamin supplementation strategy. Oral multivitamin supplements should be taken at least four hours before the dose of colesevelam.(1)

DISCUSSION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

Fat Soluble Vitamins/Orlistat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The acetate ester forms of vitamin A and vitamin E must undergo hydrolysis for absorption from the gastrointestinal tract.(1) The enzyme responsible for this hydrolysis is inhibited by orlistat.(2)

CLINICAL EFFECTS: Orlistat may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by orlistat should be borne in mind during implementation of a vitamin supplementation strategy. Patients should be strongly encouraged to take a multivitamin supplement which contains fat soluble vitamins, particularly Vitamin D as it appears most susceptible to this interaction.(4,5) Multivitamin supplements should be taken at least two hours before or after the dose of orlistat, or at bedtime.(4) Patients with chronic malabsorption syndromes should not receive orlistat.(4)

DISCUSSION: Adult patients taking orlistat without supplementation showed a greater reduction in vitamin A,D,E and beta-carotene levels compared to placebo during two or more consecutive visits in studies of 1-2 years duration; these patients had normal baseline values prior to orlistat therapy. Low vitamin values in orlistat patients were as follows: low Vitamin D 12%, low beta-carotene 6.1%, low Vitamin E 5.8%, low Vitamin A 2.2%.(4) A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption and a 60% decreased in vitamin E acetate absorption with concomitant orlistat.(4) In a study, orlistat produced the vitamin net concentration by approximately 43%.(1) In a study, no statistically significant decrease in vitamin A absorption was observed with concurrent orlistat.(2) In a study, mean vitamin D levels were significantly reduced compared with baseline after one month of orlistat therapy despite multivitamin supplementation.(5)

Oral Bisphosphonates/Oral Multivalent Cations

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Multivalent cations may bind to and inhibit the absorption of oral bisphosphonates.(1-6)

CLINICAL EFFECTS: Simultaneous administration of products containing multivalent cations may result in decreased levels of and clinical effects from oral bisphosphonates.(1-6)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Instruct patients to separate the administration times of products containing multivalent cations and oral bisphosphonates. Manufacturer recommendations regarding the separation of administration times of oral bisphosphonates and multivalent cations vary. Do NOT give multivalent cation-containing products: - until at least 30 minutes after taking alendronate(1) - within 2 hours of etidronate(2) - until at least 1 hour after taking ibandronate(3) - until at least 30 minutes after taking risedronate(4) - within 2 hours of tiludronate(5)

DISCUSSION: Multivalent cations may bind to and inhibit the absorption of oral bisphosphonates, resulting in decreased levels of and clinical effects from these agents.(1-6) Administration of aluminum- or magnesium-containing antacids 1 hour before tiludronate decreased the bioavailability of tiludronate by 60%.(5)

Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia).

Use of alendronate oral solution is contraindicated in patients at increased risk of aspiration.

Inability to stand or sit upright for at least 30 minutes.

Hypocalcemia.

Known hypersensitivity to alendronate or any ingredient in the formulation.

• Achalasia of esophagus
• Hypervitaminosis D
• Hypocalcemia
• Stricture of esophagus

• Arthralgia
• Aseptic necrosis of jaw bone
• Atypical femoral fracture
• Barrett's esophagus
• Bed-ridden
• Duodenitis
• Dysphagia
• Esophageal dysmotility
• Esophageal obstruction
• Esophageal ulcer
• Esophagitis
• Gastritis
• Hypercalcemia
• Hyperphosphatemia
• Invasive dental procedure
• Kidney stone
• Peptic ulcer
• Periodontitis
• Vitamin D deficiency

• Atrial fibrillation
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Sarcoidosis

The most common adverse effects reported in 3% or more of patients receiving alendronate in clinical studies include abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain, and nausea.

Rare or Very Rare

• Angioedema
• Aseptic necrosis of bone in orofacial region
• Aseptic necrosis of jaw bone
• Asthma exacerbation
• Atypical femoral fracture
• Atypical stress fracture
• Cholesteatoma of external ear
• Duodenal ulcer
• Esophageal perforation
• Esophageal ulcer
• Esophagitis
• Gastric ulcer
• Hypersensitivity drug reaction
• Hypocalcemia
• Hypophosphatemia
• Scleritis
• Stevens-johnson syndrome
• Stricture of esophagus
• Toxic epidermal necrolysis
• Urticaria
• Uveitis

More Frequent

• Acute abdominal pain
• Constipation
• Diarrhea
• Dyspepsia
• Gastroesophageal reflux disease
• Musculoskeletal pain
• Nausea

Less Frequent

• Abdominal distension
• Dysphagia
• Flatulence
• Headache disorder
• Vomiting

Rare or Very Rare

• Alopecia
• Arthralgia
• Black tarry stools
• Bone pain
• Dizziness
• Dysgeusia
• Flu-like symptoms
• Gastritis
• Malaise
• Myalgia
• Peripheral edema
• Pruritus of skin
• Skin photosensitivity
• Skin rash
• Vertigo

No enhanced messaging available.

The manufacturer states that safety and efficacy of alendronate have not been established in children. In a randomized trial in pediatric patients (4-18 years of age) with osteogenesis imperfecta, treatment with alendronate did not reduce the risk of fracture or bone pain; there was an increased incidence of vomiting in children receiving alendronate compared with placebo.

A characteristic physiognomy, possibly with aortic valvular stenosis, retinopathy, and mental and/or physical retardation, has occurred following prolonged hypercalcemia in infants and in neonates of mothers with hypercalcemia during pregnancy. Hypercalcemia during pregnancy may also lead to suppression of PTH concentrations in the neonate resulting in hypocalcemia, tetany, and seizures. Safe use of calcifediol, calcitriol, dihydrotachysterol (no longer commercially available in the US), paricalcitol, or ergocalciferol during pregnancy has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs.

There are no studies of alendronate in pregnant women; the drug should be used during pregnancy only if the potential benefits justify the potential risks to the mother and fetus.

Safe use of calcifediol, calcitriol, dihydrotachysterol, doxercalciferol, paricalcitol, or ergocalciferol during lactation has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs. Large doses of vitamin D analogs should not be administered to nursing women.

It is not known whether alendronate is distributed into human milk. Because many drugs are distributed into human milk, caution is advised when alendronate is used in nursing women.

No substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults. However, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.