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Drug Interactions between Didronel IV and Sandimmune

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

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Interactions between your drugs

Moderate

cycloSPORINE etidronate

Applies to: Sandimmune (cyclosporine) and Didronel IV (etidronate)

MONITOR: Coadministration of bisphosphonates with other nephrotoxic agents may increase the risk and severity of renal impairment due to additive effects on the kidney. The use of bisphosphonates has been associated with nephrotoxicity manifested as deterioration of renal function and renal failure. Cases have primarily involved intravenous formulations of the drugs such as pamidronate and zoledronic acid, especially when they are administered too rapidly. The risk of hypocalcemia may also be increased, as drug-induced renal tubular damage can lead to renal loss of calcium and other electrolytes such as magnesium. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium.

MANAGEMENT: Caution is advised if pamidronate, zoledronic acid, or other intravenous formulations of bisphosphonates must be used in patients who have recently received or are receiving treatment with other potentially nephrotoxic agents (e.g., aminoglycosides, polypeptide and polymyxin antibiotics, vancomycin, amphotericin B, adefovir, cidofovir, tenofovir, foscarnet, cisplatin, gallium nitrate, lithium, mesalamine, certain immunosuppressants, intravenous pentamidine, high intravenous dosages of methotrexate, high dosages of nonsteroidal anti-inflammatory agents). Renal function and serum electrolytes should be monitored. Patients should have serum creatinine assessed prior to each treatment, and treatment should be withheld for renal deterioration. In those treated for bone metastases, treatment should not be resumed until renal function returns to baseline.

References

  1. Kanis JA, Preston CJ, Yates AJ, Percival RC, Mundy KI, Russell RG (1983) "Effects of intravenous diphosphonates on renal function." Lancet, 1, p. 1328
  2. (2001) "Product Information. Aredia (pamidronate)." Novartis Pharmaceuticals
  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
  12. (2005) "Product Information. Boniva (ibandronate)." Roche Laboratories
View all 12 references

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Drug and food interactions

Moderate

cycloSPORINE food

Applies to: Sandimmune (cyclosporine)

GENERALLY AVOID: Administration with grapefruit juice (compared to water or orange juice) has been shown to increase blood concentrations of cyclosporine with a relatively high degree of interpatient variability. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

GENERALLY AVOID: Administration with red wine or purple grape juice may decrease blood concentrations of cyclosporine. In 12 healthy volunteers, 12 ounces total of a merlot consumed 15 minutes prior to and during cyclosporine administration (single 8 mg/kg dose of Sandimmune) decreased cyclosporine peak blood concentration (Cmax) and systemic exposure (AUC) by 38% and 30%, respectively, compared to water. The time to reach peak concentration (Tmax) doubled, and oral clearance increased 50%. Similarly, one study were 12 healthy patients were administered purple grape juice and a single dose of cyclosporine showed a 30% and a 36% decrease in cyclosporine systemic exposure (AUC) and peak blood concentration (Cmax), respectively. The exact mechanism of interaction is unknown but may involve decreased cyclosporine absorption.

MONITOR: Food has been found to have variable effects on the absorption of cyclosporine. There have been reports of impaired, unchanged, and enhanced absorption during administration with meals relative to the fasting state. The mechanisms are unclear. Some investigators found an association with the fat content of food. In one study, increased fat intake resulted in significantly increased cyclosporine bioavailability and clearance. However, the AUC and pharmacodynamics of cyclosporine were not significantly affected, thus clinical relevance of these findings may be minimal.

MANAGEMENT: Patients receiving cyclosporine therapy should be advised to either refrain from or avoid fluctuations in the consumption of grapefruits and grapefruit juice. Until more data are available, the consumption of red wine or purple grape juice should preferably be avoided or limited. All oral formulations of cyclosporine should be administered on a consistent schedule with regard to time of day and relation to meals so as to avoid large fluctuations in plasma drug levels.

References

  1. Honcharik N, Yatscoff RW, Jeffery JR, Rush DN (1991) "The effect of meal composition on cyclosporine absorption." Transplantation, 52, p. 1087-9
  2. Ducharme MP, Provenzano R, Dehoornesmith M, Edwards DJ (1993) "Trough concentrations of cyclosporine in blood following administration with grapefruit juice." Br J Clin Pharmacol, 36, p. 457-9
  3. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  4. Hollander AAMJ, Vanrooij J, Lentjes EGWM, Arbouw F, Vanbree JB, Schoemaker RC, Vanes LA, Vanderwoude FJ, Cohen AF (1995) "The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients." Clin Pharmacol Ther, 57, p. 318-24
  5. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  6. Tan KKC, Trull AK, Uttridge JA, Metcalfe S, Heyes CS, Facey S, Evans DB (1995) "Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients." Clin Pharmacol Ther, 57, p. 425-33
  7. Yee GC, Stanley DL, Pessa LJ, et al. (1995) "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet, 345, p. 955-6
  8. Ducharme MP, Warbasse LH, Edwards DJ (1995) "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther, 57, p. 485-91
  9. Ioannidesdemos LL, Christophidis N, Ryan P, Angelis P, Liolios L, Mclean AJ (1997) "Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases." J Rheumatol, 24, p. 49-54
  10. Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients." Transplantation, 62, p. 123-5
  11. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  12. Tsunoda SM, Harris RZ, Christians U, et al. (2001) "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther, 70, p. 462-7
  13. Oliveira-Freitas VL, Dalla Costa T, Manfro RC, Cruz LB, Schwartsmann G (2010) "Influence of purple grape juice in cyclosporine availability." J Ren Nutr, 20, p. 309-13
View all 13 references

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Moderate

etidronate food

Applies to: Didronel IV (etidronate)

ADJUST DOSING INTERVAL: Food, especially calcium-containing food such as dairy products, significantly decreases the bioavailability of oral etidronate.

MANAGEMENT: Oral etidronate should be administered on an empty stomach and no other food or drink should be taken within least 2 hours of administration.

References

  1. (2022) "Product Information. Didronel (etidronate)." Procter and Gamble Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Moderate

etidronate food

Applies to: Didronel IV (etidronate)

ADJUST DOSING INTERVAL: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 2 hours before or 2 hours after the bisphosphonate dose.

References

  1. (2001) "Product Information. Fosamax (alendronate)." Merck & Co., Inc
  2. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  3. "Product Information. Skelid (tiludronate)." Sanofi Winthrop Pharmaceuticals
  4. (2001) "Product Information. Actonel (risedronate)." Procter and Gamble Pharmaceuticals
  5. (2001) "Product Information. Bonefos (clodronate)." Rhone-Poulenc Rorer Canada Inc
  6. (2005) "Product Information. Boniva (ibandronate)." Roche Laboratories
View all 6 references

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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