Simultaneous use of myelosuppressives or radiation will boost the effects of cisplatin's myelosuppressive activity. The occurrence of nephrotoxicity caused by cisplatin may be intensified by concomitant treatment with antihypertensives containing furosemide, hydralazine, diazoxide, and propranolol.
Nephrotoxic substances: Concomitant administration of nephrotoxic (e.g. cephalosporins, aminoglycosides or Amphotericin B or contrast media) or ototoxic (e.g. aminoglycosides) medicinal products will potentiate the toxic effect of cisplatin on the kidneys. During or after treatment with cisplatin caution is advised with predominantly renally eliminated substances, e.g. cytostatic agents such as bleomycin and methotrexate, because of potentially reduced renal elimination.
Cisplatin given in combination with bleomycin and vinblastin can lead to a Raynaud-phenomenon. The renal toxicity of ifosfamide may be greater when used with cisplatin or in patients who have previously been given cisplatin.
Reduction of the blood's lithium values was noticed in a few cases after treatment with cisplatin combined with bleomycin and etoposide. It is therefore recommended to monitor the lithium values. It may be required to adjust the dosage of allopurinol, colchicine, probenecid, or sulfinpyrazone if used together with cisplatin, since cisplatin causes an increase in serum uric acid concentration. Cisplatin given in combination with bleomycin and vinblastin can lead to a Raynaud-phenomenon. In a study of cancer patients with metastatic or advanced tumors, docetaxel in combination with cisplatin induced more severe neurotoxic effects (dose-related and sensoric) than either drug as a single agent in similar doses.
Chelating agents like penicillamine may diminish the effectiveness of cisplatin.
In concomitant use of cisplatin and ciclosporin the excessive immunosuppression with risk of lymphoproliferation is to be taken into consideration.
Ototoxic substances: Concomitant administration of ototoxic (e.g. aminoglycosides, loop diuretics) medicinal products will potentiate the toxic effect of cisplatin on auditory function. Except for patients receiving doses of cisplatin exceeding 60 mg/m2, whose urine secretion is less than 1000 ml per 24 hours, no forced diuresis with loop diuretics should be applied in view of possible damage to the kidney tract and ototoxicity.
Ifosfamide may increase hearing loss due to cisplatin.
Weakened live vaccines: Yellow fever vaccine is strictly contraindicated because of the risk of fatal systemic vaccinal disease (see Contraindications). In view of the risk of generalised illness, it is advisable to use an inactive vaccine if available.
Oral anticoagulants: In the event of simultaneous use of oral anticoagulants, it is advisable regularly to check the INR.
Antihistamines, Phenothiazines and others: Simultaneous use of antihistamines, buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes or trimethobenzamides may mask ototoxicity symptoms (such as dizziness and tinnitus).
Anticonvulsive substances: Serum concentrations of anticonvulsive medicines may remain at subtherapeutic levels during treatment with cisplatin. Cisplatin may reduce the absorption of phenytoin resulting in reduced epilepsy control when phenytoin is given as current treatment. During cisplatin therapy starting a new anticonvulsivant treatment with phenytoin is strictly contraindicated (see Contraindications).
Pyridoxine + altretamine combination: During a randomised study of the treatment of advanced ovarian cancer, the response time was unfavourably affected when pyridoxine was used in combination with altretamine (hexamethylmelamine) and Cisplatin.
Paclitaxel: Treatment with cisplatin prior to an infusion with paclitaxel may reduce the clearance of paclitaxel by 33% and therefore can intensify neurotoxicity.