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Drug Interactions between alendronate / cholecalciferol and kanamycin

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

kanamycin alendronate

Applies to: kanamycin and alendronate / cholecalciferol

MONITOR: Coadministration of bisphosphonates and aminoglycosides may potentiate the risks of hypocalcemia and nephrotoxicity, particularly when the bisphosphonate is administered intravenously. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium, while aminoglycosides can induce renal tubular damage resulting in renal loss of calcium and magnesium. Hypomagnesemia, in turn, may also lead to peripheral parathyroid hormone resistance and impaired parathyroid hormone secretion, thus compromising the normal homeostatic response to hypocalcemia. The interaction has been reported in a 62-year-old patient with multiple myeloma who developed persistent, severe hypocalcemia and hypomagnesemia after treatment with oral clodronate and netilmicin. The electrolyte abnormalities were accompanied by increased serum creatinine concentration and grand mal seizures. Administration of bisphosphonates, especially by rapid IV injection, has also been associated with nephrotoxicity manifested as deterioration of renal function and renal failure.

MANAGEMENT: Caution is advised if bisphosphonates are used in patients who have recently received or are receiving treatment with aminoglycosides. Renal function as well as serum calcium and magnesium levels should be monitored during and after treatment, since renal loss of calcium and magnesium can continue for many weeks after cessation of aminoglycosides, as can the effect of bisphosphonates. Patients and clinicians should be alert to signs and symptoms of clinical hypocalcemia such as muscle spasms, carpopedal spasm, laryngeal spasm, tetany, convulsions, mental changes (irritability, depression, psychosis), increased intracranial pressure, papilledema, QT interval prolongation, and cardiac arrhythmias. For IV bisphosphonates, product labelings for pamidronate and zoledronic acid recommend that single doses not exceed 90 mg and 4 mg, respectively, and duration of infusion not less than 2 hours and 15 minutes, respectively.

References (11)
  1. Pedersen-Bjergaard U, Myhre J (1991) "Severe hypocalcaemia [corrected] after treatment with diphosphonate and aminoglycoside." Br Med J, 302, p. 295
  2. Kanis JA, Preston CJ, Yates AJ, Percival RC, Mundy KI, Russell RG (1983) "Effects of intravenous diphosphonates on renal function." Lancet, 1, p. 1328
  3. Osullivan TL, Akbari A, Cadnapaphornchai P (1994) "Acute renal failure associated with the administration of parenteral etidronate." Ren Fail, 16, p. 767-73
  4. Zazgornik J, Grafinger P, Biesenbach G, Hubmann R, Fridrik M (1997) "Acute renal failure and alendronate." Nephrol Dial Transplant, 12, p. 2797-8
  5. (2001) "Product Information. Zometa (zoledronic acid)." Novartis Pharmaceuticals
  6. Janssen Van Doorn K, Neyns B, Van Der Niepen P, Verbeelen D (2001) "Pamidronate-related nephrotoxicity (tubulointerstitial nephritis) in a patient with osteolytic bone metastases." Nephron, 89, p. 467-8
  7. Lockridge L, Papac RJ, Perazella MA (2002) "Pamidronate-associated nephrotoxicity in a patient with Langerhans's histiocytosis." Am J Kidney Dis, 40, E2
  8. Markowitz GS, Fine PL, Stack JI, et al. (2003) "Toxic acute tubular necrosis following treatment with zoledronate (Zometa)." Kidney Int, 64, p. 281-289
  9. Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D (2003) "Short-term, high-dose pamidronate-induced acute tubular necrosis: The postulated mechanisms of bisphosphonate nephrotoxicity." Am J Kidney Dis, 41, E18
  10. Chang JT, Green L, Beitz J (2003) "Renal failure with the use of zoledronic acid." N Engl J Med, 349, 1676-9; discussion 1676-9
  11. (2004) "Product Information. Ostac (clodronate)." Hoffmann-La Roche Limited

Drug and food interactions

Moderate

cholecalciferol food

Applies to: alendronate / cholecalciferol

MONITOR: Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

MANAGEMENT: Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

References (10)
  1. (2023) "Product Information. Drisdol (ergocalciferol)." Validus Pharmaceuticals LLC
  2. (2024) "Product Information. Fultium-D3 (colecalciferol)." Internis Pharmaceuticals Ltd
  3. (2024) "Product Information. Ostelin Specialist Range Vitamin D (colecalciferol)." Sanofi-Aventis Healthcare Pty Ltd T/A Sanofi Consumer Healthcare
  4. (2021) "Product Information. Rocaltrol (calcitriol)." Atnahs Pharma UK Ltd
  5. (2019) "Product Information. Calcitriol (calcitriol)." Strides Pharma Inc.
  6. (2024) "Product Information. Calcitriol (GenRx) (calcitriol)." Apotex Pty Ltd
  7. (2022) "Product Information. Ergocalciferol (ergocalciferol)." RPH Pharmaceuticals AB
  8. (2020) "Product Information. Sandoz D (cholecalciferol)." Sandoz Canada Incorporated
  9. Fischer V, Haffner-Luntzer M, Prystaz K, et al. (2024) Calcium and vitamin-D deficiency marginally impairs fracture healing but aggravates posttraumatic bone loss in osteoporotic mice. https://www.nature.com/articles/s41598-017-07511-2
  10. National Institutes of Health Office of Dietary Supplements (2024) Vitamin D https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h37
Moderate

alendronate food

Applies to: alendronate / cholecalciferol

ADJUST DOSING INTERVAL: Food significantly decreases the bioavailability of alendronate, possibly to negligible levels.

MANAGEMENT: Alendronate should be administered with 6 to 8 ounces of plain water, at least 30 minutes before the first food, beverage, or medication of the day. Patients should remain upright for at least 30 minutes following administration of alendronate.

References (1)
  1. (2001) "Product Information. Fosamax (alendronate)." Merck & Co., Inc

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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