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Drug Interactions between Cytovene and Proben-C

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

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Interactions between your drugs

Moderate

probenecid ganciclovir

Applies to: Proben-C (colchicine / probenecid) and Cytovene (ganciclovir)

MONITOR: The coadministration of probenecid and ganciclovir may result in elevated plasma concentrations of ganciclovir. In 10 subjects with HIV infection, probenecid (500 mg orally every 6 hours) increased the peak plasma concentration and area under the concentration-time curve of ganciclovir (1 gram orally every 8 hours) by an average of 40% and 53%, respectively. Renal clearance decreased an average of 22%. The mechanism of the interaction is competitive inhibition of ganciclovir renal tubular secretion by probenecid.

MANAGEMENT: Caution is advised if ganciclovir or its prodrug, valganciclovir, must be used concomitantly with probenecid. Close monitoring for toxicities associated with ganciclovir such as myelosuppression is recommended during concurrent therapy.

References

  1. (2002) "Product Information. Cytovene (ganciclovir)." Genentech
  2. (2001) "Product Information. Valcyte (valganciclovir)." Roche Laboratories
  3. Cimoch PJ, Lavelle J, Pollard R, et al. (1998) "Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine, and probenecid in HIV-infected subjects." J Acquire Immune Defic Hum Retrovirol, 17, p. 227-34

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Moderate

ganciclovir colchicine

Applies to: Cytovene (ganciclovir) and Proben-C (colchicine / probenecid)

GENERALLY AVOID: The use of ganciclovir or its prodrug, valganciclovir, with other drugs associated with myelosuppression and/or nephrotoxicity may increase the risk and severity of these adverse reactions due to additive effects on the kidney and bone marrow. Valganciclovir is rapidly and extensively converted to ganciclovir, which has had the following adverse reactions observed with its treatment when used alone: severe leucopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow depression, aplastic anemia, increased serum creatinine levels, and acute renal failure. Additionally, ganciclovir is primarily renally excreted; therefore, patients with impaired renal function will have increased concentrations of ganciclovir and may be at an even greater risk of experiencing adverse reactions from treatment. Theoretically when two or more medications with similar side effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased.

MANAGEMENT: Ganciclovir or its prodrug, valganciclovir, should generally not be combined with other drugs associated with myelosuppression and/or nephrotoxicity unless the benefits are anticipated to outweigh the potential risks. Extreme caution is advised if they are used in patients who have recently received or are receiving treatment with myelotoxic and/or nephrotoxic drugs, and vice versa. If coadministration is required, reduced dosages of one or more of the drugs may be required, and the patient should be monitored for the development of hematologic and/or renal adverse effects both during and after discontinuation of therapy.

References

  1. (2002) "Product Information. Cytovene (ganciclovir)." Genentech
  2. (2001) "Product Information. Valcyte (valganciclovir)." Roche Laboratories
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
View all 4 references

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Drug and food interactions

Major

colchicine food

Applies to: Proben-C (colchicine / probenecid)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the serum concentrations of colchicine. Clinical toxicity including myopathy, neuropathy, multiorgan failure, and pancytopenia may occur. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism and P-glycoprotein efflux in the gut wall by certain compounds present in grapefruits. A published case report describes an eight-year-old patient with familial Mediterranean fever who developed acute clinical colchicine intoxication after ingesting approximately one liter of grapefruit juice per day for two months prior to hospital admission while being treated with colchicine 2 mg/day. Her condition progressed to circulatory shock and multiorgan failure, but she recovered with supportive therapy after 24 days in the hospital. In a study of 21 healthy volunteers, administration of 240 mL grapefruit juice twice a day for 4 days was found to have no significant effect on the pharmacokinetics of a single 0.6 mg dose of colchicine. However, significant interactions have been reported with other CYP450 3A4 inhibitors such as clarithromycin, diltiazem, erythromycin, ketoconazole, ritonavir, and verapamil.

MANAGEMENT: Patients treated with colchicine should be advised to avoid the consumption of grapefruit and grapefruit juice, and to contact their physician if they experience symptoms of colchicine toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.

References

  1. Pettinger WA (1975) "Clonidine, a new antihypertensive drug." N Engl J Med, 293, p. 1179-80
  2. Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E (1992) "Acute colchicine intoxication: possible role of erythromycin administration." J Rheumatol, 19, p. 494-6
  3. Schiff D, Drislane FW (1992) "Rapid-onset colchicine myoneuropathy." Arthritis Rheum, 35, p. 1535-6
  4. Putterman C, Ben-Chetrit E, Caraco Y, Levy M (1991) "Colchicine intoxication: clinical pharmacology, risk factors, features, and management." Semin Arthritis Rheum, 21, p. 143-55
  5. Boomershine KH (2002) "Colchicine-induced rhabdomyolysis." Ann Pharmacother, 36, p. 824-6
  6. (2003) "Severe colchicine-macrolide interactions." Prescrire Int, 12, p. 18-9
  7. Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ (1996) "Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation." Biochem Pharmacol, 53, p. 111-6
  8. Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C (2001) "Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration." Clin Nephrol, 55, p. 181-2
  9. Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche P (2004) "Acute colchicine intoxication during clarithromycin administration." Ann Pharmacother, 38, p. 2074-7
  10. Wilbur K, Makowsky M (2004) "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy, 24, p. 1784-92
  11. Hung IF, Wu AK, Cheng VC, et al. (2005) "Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study." Clin Infect Dis, 41, p. 291-300
  12. Cheng VC, Ho PL, Yuen KY (2005) "Two probable cases of serious drug interaction between clarithromycin and colchicine." South Med J, 98, p. 811-3
  13. Akdag I, Ersoy A, Kahvecioglu S, Gullulu M, Dilek K (2006) "Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure." J Nephrol, 19, p. 515-7
  14. van der Velden W, Huussen J, Ter Laak H, de Sevaux R (2008) "Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin." Neth J Med, 66, p. 204-6
  15. Goldbart A, Press J, Sofer S, Kapelushnik J (2000) "Near fatal acute colchicine intoxication in a child. A case report." Eur J Pediatr, 159, p. 895-7
  16. (2008) "Colchicine: serious interactions." Prescrire Int, 17, p. 151-3
  17. (2009) "Product Information. Colcrys (colchicine)." AR Scientific Inc
  18. Dahan A, Amidon GL (2009) "Grapefruit juice and its constitueants augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein." Pharm Res, 26, p. 883-92
  19. McKinnell J, Tayek JA (2009) "Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis." J Clin Rheumatol, 15, p. 303-5
View all 19 references

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Moderate

ganciclovir food

Applies to: Cytovene (ganciclovir)

ADJUST DOSING INTERVAL: Food delays but enhances the oral absorption and bioavailability of ganciclovir capsules, possibly due to prolongation of gastrointestinal transit time. In 20 HIV- and CMV-seropositive subjects, ganciclovir dosing (1000 mg every 8 hours) following a standardized high-fat breakfast increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ganciclovir by an average of 15% and 22%, respectively, compared to dosing after an overnight fast. The time to reach peak plasma concentration (Tmax) was prolonged from 1.8 to 3 hours. In another study of 15 such patients, administration of ganciclovir (2000 mg) within 30 minutes following a high-fat breakfast increased the Cmax and AUC an average of 111% and 114%, respectively, compared to administration in the fasting state (i.e. at least 1 hour before or 2 hours after a meal or snack). Over the total day of dosing (2000 mg orally three times a day), there was a mean increase of 48% and 97% in Cmax and AUC, respectively, and a 36% decrease in half-life during administration with meals.

MANAGEMENT: To ensure maximal oral absorption, oral ganciclovir should be administered with or immediately after a meal.

References

  1. (2002) "Product Information. Cytovene (ganciclovir)." Genentech
  2. Lavelle J, Follansbee S, Trapnell CB, Buhles WC, Griffy KG, Jung D, Dorr A, Conner J (1996) "Effect of food on the relative bioavailability of oral ganciclovir." J Clin Pharmacol, 36, p. 238-41
  3. Jung D, Griffy K, Dorr A (1999) "Effect of food on high-dose oral ganciclovir disposition in HIV-positive subjects." J Clin Pharmacol, 39, p. 161-5

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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

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