FOSAMAX PLUS D

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FOSAMAX PLUS D (FOSAMAX PLUS D).

How it works

Alendronate, a bisphosphonate, inhibits osteoclast-mediated bone resorption by binding to hydroxyapatite and interfering with the mevalonate pathway, leading to osteoclast apoptosis. Cholecalciferol (vitamin D3) promotes intestinal calcium absorption and bone mineralization.

What the body does with it

Metabolism	Alendronate is not metabolized in humans; it is excreted unchanged in urine. Cholecalciferol is hydroxylated in the liver to 25-hydroxyvitamin D3 and further in the kidney to 1,25-dihydroxyvitamin D3.
Excretion	Alendronate: ~50% excreted unchanged in urine; remainder is taken up by bone and slowly eliminated. No biliary or fecal excretion of intact drug. Cholecalciferol: ~50% excreted in bile via feces; less than 1% in urine.
Half-life	Alendronate: Terminal half-life in bone is estimated at 10+ years due to slow release from the skeleton. Cholecalciferol: Half-life of 25-hydroxyvitamin D is ~15 days.
Protein binding	Alendronate: ~78% bound to plasma proteins. Cholecalciferol: ~50% bound to vitamin D-binding protein (DBP) with high affinity.
Volume of Distribution	Alendronate: Vd 0.3–0.4 L/kg, indicating distribution into bone and extracellular fluid. Cholecalciferol: Vd ~0.2 L/kg, distributing to fat, liver, and muscle.
Bioavailability	Alendronate: Oral bioavailability <1% (0.5–0.7%) when taken on an empty stomach with plain water; significantly reduced by food. Cholecalciferol: Oral bioavailability ~60-70% when taken with food (especially fatty meals); less than 10% if taken on empty stomach.
Onset of Action	Alendronate: Inhibition of bone resorption begins within days, with maximal reduction in bone turnover markers at 3–6 months. Cholecalciferol: Onset of action for increasing serum 25-hydroxyvitamin D occurs within hours to days after administration.
Duration of Action	Alendronate: Suppression of bone turnover persists for weeks after cessation due to prolonged bone binding. Cholecalciferol: Duration of effect on vitamin D levels lasts for weeks to months.

Classification & Brands

Dosing & administration

One tablet (alendronate 70 mg / cholecalciferol 2800 IU) orally once weekly.

Dosage form	TABLET
Renal impairment	Contraindicated if GFR <35 mL/min; no dosage adjustment required for GFR ≥35 mL/min.
Liver impairment	No specific dosage adjustment recommended based on Child-Pugh class; use caution in severe hepatic impairment.
Pediatric use	Safety and effectiveness not established; not recommended for use in pediatric patients.
Geriatric use	No specific dosage adjustment required; ensure adequate calcium and vitamin D intake and monitor renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FOSAMAX PLUS D (FOSAMAX PLUS D).

Breastfeeding	Unknown if excreted in human milk; M/P ratio not established. Bisphosphonates likely to be present in breast milk; potential for bone growth suppression in infant. Avoid use during breastfeeding or discontinue breastfeeding.
Teratogenic Risk	Category D: Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. First trimester: Risk of hypocalcemia-related fetal effects. Second and third trimesters: Potential for fetal skeletal abnormalities due to bisphosphonate incorporation into bone matrix. Cases of neonatal hypocalcemia and transient respiratory distress reported.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to any component","Hypocalcemia","Inability to sit or stand upright for at least 30 minutes","Renal impairment with creatinine clearance <35 mL/min"]

Clinical Precautions

Precautions

["Hypocalcemia must be corrected before therapy","Severe musculoskeletal pain","Osteonecrosis of the jaw","Atypical femur fractures","Renal impairment (CrCl <35 mL/min contraindicated)","Esophageal irritation and stricture risk; instruct to take with full glass of water and remain upright for 30 minutes","Hypersensitivity reactions"]

Clinical Tips & Counseling

Drug interactions

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FOSAMAX PLUS D

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FOSAMAX PLUS D (FOSAMAX PLUS D).

How it works

What the body does with it

Metabolism	Alendronate is not metabolized in humans; it is excreted unchanged in urine. Cholecalciferol is hydroxylated in the liver to 25-hydroxyvitamin D3 and further in the kidney to 1,25-dihydroxyvitamin D3.
Excretion	Alendronate: ~50% excreted unchanged in urine; remainder is taken up by bone and slowly eliminated. No biliary or fecal excretion of intact drug. Cholecalciferol: ~50% excreted in bile via feces; less than 1% in urine.
Half-life	Alendronate: Terminal half-life in bone is estimated at 10+ years due to slow release from the skeleton. Cholecalciferol: Half-life of 25-hydroxyvitamin D is ~15 days.
Protein binding	Alendronate: ~78% bound to plasma proteins. Cholecalciferol: ~50% bound to vitamin D-binding protein (DBP) with high affinity.
Volume of Distribution	Alendronate: Vd 0.3–0.4 L/kg, indicating distribution into bone and extracellular fluid. Cholecalciferol: Vd ~0.2 L/kg, distributing to fat, liver, and muscle.
Bioavailability	Alendronate: Oral bioavailability <1% (0.5–0.7%) when taken on an empty stomach with plain water; significantly reduced by food. Cholecalciferol: Oral bioavailability ~60-70% when taken with food (especially fatty meals); less than 10% if taken on empty stomach.
Onset of Action	Alendronate: Inhibition of bone resorption begins within days, with maximal reduction in bone turnover markers at 3–6 months. Cholecalciferol: Onset of action for increasing serum 25-hydroxyvitamin D occurs within hours to days after administration.
Duration of Action	Alendronate: Suppression of bone turnover persists for weeks after cessation due to prolonged bone binding. Cholecalciferol: Duration of effect on vitamin D levels lasts for weeks to months.

Classification & Brands

Dosing & administration

One tablet (alendronate 70 mg / cholecalciferol 2800 IU) orally once weekly.

Dosage form	TABLET
Renal impairment	Contraindicated if GFR <35 mL/min; no dosage adjustment required for GFR ≥35 mL/min.
Liver impairment	No specific dosage adjustment recommended based on Child-Pugh class; use caution in severe hepatic impairment.
Pediatric use	Safety and effectiveness not established; not recommended for use in pediatric patients.
Geriatric use	No specific dosage adjustment required; ensure adequate calcium and vitamin D intake and monitor renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FOSAMAX PLUS D (FOSAMAX PLUS D).

Breastfeeding	Unknown if excreted in human milk; M/P ratio not established. Bisphosphonates likely to be present in breast milk; potential for bone growth suppression in infant. Avoid use during breastfeeding or discontinue breastfeeding.
Teratogenic Risk	Category D: Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. First trimester: Risk of hypocalcemia-related fetal effects. Second and third trimesters: Potential for fetal skeletal abnormalities due to bisphosphonate incorporation into bone matrix. Cases of neonatal hypocalcemia and transient respiratory distress reported.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to any component","Hypocalcemia","Inability to sit or stand upright for at least 30 minutes","Renal impairment with creatinine clearance <35 mL/min"]