Cyclophosphamide Amiodarone

The calcium channel blocker mibefradil (Posicor ) was removed from the market in 1998. The headline for the Pink Sheets article describing this action was "Posicor Withdrawal Reflects Complexity of Interaction Profile" (59). Products identified as potentially dangerous in combination with mibefradil included cardiac drugs, such as amiodarone, flecainide, and propafenone oncologic products, such as tamoxifen, cyclophosphamide, etoposide, ifosfamide, and vinblastine and the immunosuppressant medications cyclosporine and tacrolimus. The sponsor s decision to withdraw mibefradil was based on the complexity of the drug interaction information that would have to be communicated to ensure safe usage. 

Both amiodarone and cyclophosphamide can cause lung damage. 

Interstitial pneumonitis has been reported in a 59-year-old man, who had taken amiodarone for 18 months, 18 days after a single dose of cyclophosphamide 1 year before he had also received six cycles of chemotherapy containing cyclophosphamide, vincristine, and prednisone, followed by four cycles of cisplatin, cytarabine, and dexamethasone (253). 

Bhagat R, Sporn TA, Long GD, Folz RJ. Amiodarone and cyclophosphamide potential for enhanced lung toxicity. Bone Marrow Transplant 2001 27(10) 1109-11. 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Early-onset pulmonary toxicity occurred in one patient taking amiodarone after high-dose cyclophosphamide was given. Fatal pulmonary toxicity occurred in another patient taking amiodarone after a single dose of cyclophosphamide. 

A patient with dendritic cell carcinoma who had been taking amiodarone for 18 months, and who had received 6 cycles of chemotherapy ineluding cyclophosphamide over the previous 12 months, was admitted to hospital with progressive shortness of breath 18 days after being given a single 4000-mg/m dose of eyelophosphamide. He was found to have interstitial... 

Pulmonary toxicity may occur in about 10% of patients given amiodarone. Pulmonary toxicity due to cyclophosphamide may occur between 1 to 6 months after exposure or occttr as a more insidiotts form after about 6 months. The early onset of symptorrrs in the patients described above suggests accelerated mechanisms of ptrlmonary toxicity. Both cyclophosphamide and amiodarone pulmonary toxicity appear to be erthanced by oxygen and the combination of cyclophosphamide with amiodarone may enhance oxidative stress and therefore ptrlmonary toxicity. 

Although information seems to be limited to the two case reports cited, the potential for both cyclophosphamide and amiodarone to cause pulmonary toxicity is established. Be alert to the possibility of enhanced pulmonary toxicity if these drugs are given together. 

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