FOSAMAX PLUS D
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FOSAMAX PLUS D (FOSAMAX PLUS D).
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.
| 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. |
| Molecular Weight | 325.12 |
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. |
| 1st trimester | Alendronate is contraindicated during pregnancy due to potential fetal harm. Animal studies show delayed delivery, maternal and fetal toxicity at high doses. There is a risk of hypocalcemia and skeletal abnormalities. |
| 2nd trimester | Contraindicated. Data insufficient to support safety. Potential for fetal skeletal effects and maternal hypocalcemia. |
| 3rd trimester | Contraindicated. Risk of fetal skeletal effects and maternal electrolyte disturbances. Use only if clearly needed and no alternative. |
Clinical note
Comprehensive clinical and safety monograph for FOSAMAX PLUS D (FOSAMAX PLUS D).
| Placental transfer | Bisphosphonates cross the placenta. Alendronate has been detected in fetal tissues in animal studies; human data limited but assumed transfer. May accumulate in fetal bone. |
| Breastfeeding | Alendronate is excreted into breast milk in low amounts (estimated relative infant dose <1%). However, due to potential for bone growth suppression and hypocalcemia in the infant, caution is advised. Cholecalciferol (vitamin D) is present in breast milk but overdose unlikely. Consider alternative therapies. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to alendronate or any componentHypocalcemiaInability to stand or sit upright for at least 30 minutesSevere renal impairment (CrCl <35 mL/min)Esophageal abnormalities that delay esophageal emptying (stricture, achalasia)
| 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 |
| Food/Dietary | Avoid all food and beverages (including mineral water, coffee, tea, juice, milk, and supplements) for at least 30 minutes post-dose. Plain tap water only. Calcium-rich foods and supplements should be taken at other times of day. High-fiber or high-fat meals may further reduce absorption if taken too soon. |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor maternal serum calcium, phosphate, magnesium, and vitamin D levels. Assess fetal growth by ultrasound. Monitor neonatal calcium levels postpartum. Evaluate for neonatal hypocalcemia signs (tetany, seizures). |
| Fertility Effects | No human data on fertility; animal studies show no impairment of fertility at clinically relevant doses. Potential for delayed ovulation due to altered calcium metabolism, but not confirmed. |
| Clinical Pearls | Fosamax Plus D combines alendronate (70 mg) with vitamin D3 (2800 IU or 5600 IU) for osteoporosis. Administer on an empty stomach upon rising with plain water only; wait at least 30 minutes before first food, drink, or other medications to minimize esophageal irritation. Monitor for hypocalcemia before initiation. Use with caution in renal impairment (CrCl <35 mL/min contraindicated). |
| Patient Advice | Take tablet immediately after waking with a full glass of plain water (6-8 oz). · Do not eat, drink, or take other medications for at least 30 minutes after taking. · Remain upright (sitting or standing) for at least 30 minutes to prevent esophageal irritation. · Avoid lying down until after first food of the day. · Supplement with calcium if dietary intake is inadequate; vitamin D is provided in the tablet. · Report new or worsening bone, joint, or muscle pain; difficulty swallowing; or jaw pain/dental issues. |