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Interactions between Copiktra and Topotecan

1 drug interaction and 12 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

topotecan duvelisib

Applies to: topotecan and Copiktra (duvelisib)
Monitor

The use of topotecan with other cytotoxic agents is likely to result in greater myelosuppression due to additive or synergistic pharmacologic effects. Severe neutropenia and neutropenic sepsis resulting in death were reported with topotecan and cisplatin.

Management

Caution is advised if topotecan is used with other cytotoxic agents. Dosage reductions may be required, and bone marrow function should be closely monitored. Patients should be advised to contact their physician if they develop signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, or signs of infection such as fever, chills, sore throat, body aches, and other influenza-like symptoms.

References (1)
  1. (2001) "Product Information. Hycamtin (topotecan)." SmithKline Beecham

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

duvelisib Food/Lifestyle

Applies to: Copiktra (duvelisib)
Monitor

Grapefruit or grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

Management

Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References (32)
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  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. 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
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
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Disease interactions

11 potential interactions Applies to: 10 conditions, including Diarrhea, Fever, Liver Disease, Infection, and Bleeding Disorder.

Bleeding Disorder

Major:

topotecan

Topotecan has a major potential interaction with Bleeding Disorder.

Topotecan induces myelosuppression. Severe thrombocytopenia (< 25,000/mm3) has been reported during topotecan therapy. Patients should be instructed to immediately report any signs or symptoms suggesting bleeding such as petechiae, purpura, hematuria, or melena. Close clinical monitoring of hematopoietic function is recommended. Therapy with topotecan should not be initiated in patients with platelet counts < 100,000/mm3. Subsequent courses of topotecan should be withheld until platelet counts exceed 100,000/mm3.

Bone Marrow Depression/Low Blood Counts

Major:

topotecan

Topotecan has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Topotecan induces myelosuppression. Severe neutropenia (< 500/mm3), severe thrombocytopenia (< 25,000/mm3), and severe anemia (< 8 g/dl) have been reported frequently. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended. Therapy with topotecan should not be initiated in patients with neutrophil counts < 1500/mm3 and/or platelet counts < 100,000/mm3. Subsequent courses of topotecan should be withheld until neutrophil counts exceed 1000/mm3, platelet counts exceed 100,000/mm3, and/or hemoglobin levels are at least 9 g/dl.

Diarrhea

Moderate:

topotecan

Topotecan has a moderate potential interaction with Diarrhea.

Topotecan capsules can cause severe and life-threatening diarrhea that may require hospitalization. It is recommended to withhold treatment for severe diarrhea. Manage diarrhea caused by topotecan aggressively and do no administer topotecan capsules to patients with Grade 3 or 4 diarrhea. Reduce the dose of therapy after recovery to Grade 1 or less. Close monitoring is recommended.

Fever

Major:

topotecan

Topotecan has a major potential interaction with Fever.

Topotecan induces myelosuppression. Severe neutropenia (< 500/mm3), severe thrombocytopenia (< 25,000/mm3), and severe anemia (< 8 g/dl) have been reported frequently. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended. Therapy with topotecan should not be initiated in patients with neutrophil counts < 1500/mm3 and/or platelet counts < 100,000/mm3. Subsequent courses of topotecan should be withheld until neutrophil counts exceed 1000/mm3, platelet counts exceed 100,000/mm3, and/or hemoglobin levels are at least 9 g/dl.

Infection

Major:

Copiktra

The duvelisib in Copiktra has a major potential interaction with Infection.

Any infection should be treated prior to initiation of treatment with duvelisib. Serious, including fatal infections have occurred in patients receiving treatment with this drug. The most common serious infections were pneumonia (including fatal pneumocystis jirovecii pneumonia, PJP), sepsis, and lower respiratory infections. Advise patients to report any new or worsening signs and symptoms of infection. In some cases, treatment might need to be suspended while the infection is treated. Prophylaxis for PJP should be provided during treatment, and in some cases also prophylactic antivirals should be considered in patients with history of CMV infection to avoid CMV reactivation.

Major:

topotecan

Topotecan has a major potential interaction with Infection.

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

Liver Disease

Moderate:

Copiktra

The duvelisib in Copiktra has a moderate potential interaction with Liver Disease.

Bilirubin and ALT and/or AST elevation has been reported in patients receiving duvelisib. Monitor hepatic function in all patients during treatment with duvelisib. Caution and close monitoring is advised in patients with hepatic impairment.

Neutropenia

Moderate:

Copiktra

The duvelisib in Copiktra has a moderate potential interaction with Neutropenia.

Caution and close monitoring is advised when starting treatment in patients with neutropenia. Grade 3 or 4 neutropenia has been reported in 42% of patients receiving treatment. Monitor neutrophil counts at least every 2 weeks for the first 2 months of duvelisib therapy, and at least weekly in patients with neutrophil counts < 1.0 Gi/L (Grade 3-4). Withhold treatment with duvelisib in patients presenting with neutrophil counts < 0.5 Gi/L (Grade 4). Monitor until ANC is > 0.5 Gi/L, and then resume duvelisib at same dose for the first occurrence or a reduced dose for subsequent occurrence.

Noninfectious Colitis

Major:

Copiktra

The duvelisib in Copiktra has a major potential interaction with Noninfectious Colitis.

Serious, including fatal diarrhea or colitis has been reported in 18% of patients receiving treatment with duvelisib. Patients with history of colitis should be monitored closely for any signs or symptoms. Advise patients to report any new or worsening diarrhea. Patients presenting with abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, or with diarrhea that is noninfectious should be followed closely and supportive therapy should be initiated based on severity (antidiarrheal agents, to enteric acting or systemic steroids if needed). A diagnostic work- up to determine etiology, including colonoscopy, should be performed. Monitor at least weekly. Upon resolution of the diarrhea or colitis, treatment can be restarted at a reduced dose. Treatment should be discontinued for recurrent Grade 3 diarrhea or recurrent colitis of any grade.

Pulmonary Impairment

Moderate:

topotecan

Topotecan has a moderate potential interaction with Pulmonary Impairment.

Fatal cases of interstitial lung disease (ILD) have occurred with the use of topotecan. Risk factors include a history of ILD, pulmonary fibrosis, lung cancer, thoracic radiation, and use of pneumotoxic drugs and/or colony stimulating factors. It is recommended to monitor patients for pulmonary symptoms indicative of ILD and permanently discontinue treatment for confirmed ILD.

Renal Dysfunction

Major:

topotecan

Topotecan has a major potential interaction with Renal Dysfunction.

Topotecan is partially eliminated by the kidney. Approximately 30% of topotecan is excreted in the urine. Plasma clearance of topotecan was reduced 33% in patients with mild renal impairment (creatinine clearance of 40 to 60 mL/min) and 66% in patients with moderate renal impairment (creatinine clearance of 20 to 40 mL/min). Therapy with topotecan should be administered cautiously and at a reduced dosage in patients with moderate to severe renal dysfunction.

More resources

Copiktra

A total of 666 drugs are known to interact with Copiktra.

topotecan

A total of 453 drugs are known to interact with topotecan.

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.