Drug General Information (ID: DDI8FU3DPO)
Drug Name			Zoledronic acid		Drug Info		Tobramycin		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Bone Density Conservation Agents				Antibiotics
Structure

Mechanism of Zoledronic acid-Tobramycin Interaction (Severity Level: Moderate)
Increased risk of hypocalcemia Click to Show/Hide Mechanism Graph
Drug Name		Zoledronic acid				Tobramycin
Mechanism		Hypocalcemia				Hypocalcemia
Key Mechanism Factor 1
		Factor Name		Hypocalcemia
		Factor Description		Hypocalcemia is a low level of calcium found in a blood test. It can cause symptoms such as tingling, muscle cramps and heart rhythm problems that can range from mild to life-threatening.
Mechanism Description		Increased risk of hypocalcemia by the combination of Zoledronic acid and Tobramycin

Recommended Action
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.

References
1	Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D "Short-term, high-dose pamidronate-induced acute tubular necrosis: The postulated mechanisms of bisphosphonate nephrotoxicity." Am J Kidney Dis 41 (2003): E18. [PMID: 12778436]
2	Chang JT, Green L, Beitz J "Renal failure with the use of zoledronic acid." N Engl J Med 349 (2003): 1676-9 discussion 1676-9. [PMID: 14573746]
3	Janssen Van Doorn K, Neyns B, Van Der Niepen P, Verbeelen D "Pamidronate-related nephrotoxicity (tubulointerstitial nephritis) in a patient with osteolytic bone metastases." Nephron 89 (2001): 467-8. [PMID: 11721169]
4	Kanis JA, Preston CJ, Yates AJ, Percival RC, Mundy KI, Russell RG "Effects of intravenous diphosphonates on renal function." Lancet 1 (1983): 1328. [PMID: 6134112]
5	Lockridge L, Papac RJ, Perazella MA "Pamidronate-associated nephrotoxicity in a patient with Langerhans's histiocytosis." Am J Kidney Dis 40 (2002): E2. [PMID: 12087588]
6	Markowitz GS, Fine PL, Stack JI, et al. "Toxic acute tubular necrosis following treatment with zoledronate (Zometa)." Kidney Int 64 (2003): 281-289. [PMID: 12787420]
7	Osullivan TL, Akbari A, Cadnapaphornchai P "Acute renal failure associated with the administration of parenteral etidronate." Ren Fail 16 (1994): 767-73. [PMID: 7899588]
8	Pedersen-Bjergaard U, Myhre J "Severe hypocalcaemia [corrected] after treatment with diphosphonate and aminoglycoside." Br Med J 302 (1991): 295. [PMID: 1825614]
9	Product Information. Ostac (clodronate). Hoffmann-La Roche Limited, Mississauga, IA.
10	Product Information. Zometa (zoledronic acid). Novartis Pharmaceuticals, East Hanover, NJ.
11	Zazgornik J, Grafinger P, Biesenbach G, Hubmann R, Fridrik M "Acute renal failure and alendronate." Nephrol Dial Transplant 12 (1997): 2797-8. [PMID: 9430905]