Abiplatin 1 mg/ml

/ Salomon, Levin & Elstein Ltd

Cisplatin may be administered in doses ranging from 20-120 mg/m2, either alone or in combination with other antineoplastic agents. Factors influencing the decision of the dose to be given include the condition being treated, concomitant therapy, and the toxic manifestations in the individual patient. A repeat course of cisplatin should not be administered until the serum creatinine is below 1.5 mg/100 ml, and/or the BUN is below 25 mg/100 ml. A repeat course should not be administered until circulating blood elements are at an acceptable level (platelets > 100,000/mm3, WBC>4,000/mm3). Subsequent doses of cisplatin should not be administered until an audiometric analysis indicates that auditory acuity is within normal limits.
Maintenance Therapy: Maintenance therapy for patients who respond to the above regimen consists of vinblastine 0.3 mg/kg body weight IV, every 4 weeks for a total of 2 years.
Metastatic Ovarian Tumors: As a single agent, administer 100 mg/m2 cisplatin IV, once every 4 weeks.An effective combination for the treatment of patients with metastatic ovarian tumors includes cisplatin and doxorubicin in the following dosage: Cisplatin50 mg/m2 IV, once every 3 weeks (day 1).
Doxorubicin:50 mg/m2 IV, once every 3 weeks (day 1).The two agents are administered sequentially.
Advanced Bladder Cancer: Cisplatin should be administered as a single agent at a dose of 50-70 mg/m2 IV once every 3-4 weeks depending on the extent of prior exposure to radiation therapy and/or prior chemotherapy. For heavily pretreated patients, an initial dose of 50 mg/m2 repeated every 4 weeks is recommended.

Indicated as palliative therapy, to be employed either as a single agent or in established combination therapy with other chemotherapeutic agents in the following indications:
Metastatic Testicular Tumors: In established combination therapy with other approved chemotherapeutic agents, in patients with metastatic testicular tumors who have already received appropriate surgical and/or radiotherapeutic procedures.
Metastatic Ovarian Tumors: In established combination therapy with other approved chemotherapeutic agents, in patients
with metastatic ovarian tumors who have already received appropriate surgical and/or radiotherapeutic procedures. An established combination consists of cisplatin and cyclophosphamide. As a single agent, is indicated as secondary therapy in patients with metastatic ovarian tumors refractory to standard chemotherapy that have not previously received therapy.
Advanced Bladder Cancer: Indicated as a single agent for patients with transitional cell bladder cancer, which is no longer amenable to local treatments such as surgery and/or radiotherapy.

Abiplatin is contraindicated in patients with a history of allergic reactions to the product or other platinum containing compounds, or any component of the formulation.
Abiplatin is contraindicated in patients with myelosuppression, with neuropathy caused by cisplatin in patients who are dehydrated (pre- and post-hydration is required to prevent serious renal dysfunction), and those with pre-existing renal impairment (creatinine clearance < 60 ml/min) or hearing impairment due to the fact that Abiplatin is nephrotoxic and neurotoxic (in particular ototoxic). These toxicities may be cumulative if disorders of this type pre-exist. Patients receiving cisplatin should not breastfeed. Concurrent administration of yellow fever vaccine is contraindicated.

The serum creatinine, BUN and creatinine clearance should be measured prior to initiating therapy and prior to each subsequent course. Use in pregnancy. Careful audiometry monitoring should be performed prior to initiation of therapy and prior to subsequent doses. Peripheral blood counts should be monitored weekly. Therapy should be discontinued when neurological symptoms are first observed.
See prescribing information for full details.

Nephrotoxicity, electrolyte disturbances, ototoxicity, neuropathies. Myelosuppression occurs in 25-30% of patients treated. Leukopenia and thrombocytopenia are more pronounced at higher doses. Nausea and vomiting, anaphylactic-like reactions, ocular toxicity, hyperuricemia, cardiac abnormalities, elevated SGOT.
See prescribing information for full details.

Nephrotoxic substances: Concomitant administration of nephrotoxic (e.g. cephalosporins, aminoglycosides, 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 renal eliminated substances, e.g. cytostatic agents such as bleomycin and methotrexate, because of potentially reduced renal elimination. 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.
The occurrence of nephrotoxicity caused by cisplatin may be intensified by concomitant treatment with antihypertensives containing furosemide, hydralazine, diazoxide, and propranolol. 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. 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.
Simultaneous use of ifosphamide causes increased protein excretion.
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. In view of the risk of generalised illness, it is advisable to use an
inactive vaccine if available. Use of living virus vaccinations is not recommended given within three months following the end of the cisplatin treatment.
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. May reduce the absorption of phenytoin resulting in reduced epilepsy control when phenytoin is given as current treatment. During therapy starting a new anticonvulsivant treatment with phenytoin is strictly contraindicated.
Pyroxidine + 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 Abiplatin .
Paclitaxel: Treatment with cisplatin prior to an infusion with paclitaxel may reduce the clearance of paclitaxel by 33% and therefore can intensify neurotoxicity.
Other: Simultaneous use of myelosuppressives or radiation will boost the effects of cisplatin’s myelosuppressive activity. 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.

Pregnancy: There is insufficient data about the use of cisplatin in pregnant women. However, based on the pharmacological properties, cisplatin is suspected to cause serious birth defects. Animal studies have shown reproductive toxicity and transplacental carcinogenity. Abiplatin may be toxic to the foetus when administered to a pregnant woman. Cisplatin should not be used during pregnancy unless clearly necessary. During treatment with Abiplatin and for a minimum of the following 6 months, appropriate measures must be taken to avoid pregnancy; this applies to patients of both sexes.Genetic consultation is recommended if the patient wishes to have children after ending the treatment.
A preconceptual consult is recommended when patients wish to have children after treatment with cisplatin.Since a treatment with cisplatin may cause irreversible infertility, it is recommended that men, who wish to become fathers in the future, ask for advice regarding cryoconservation of their sperm prior to treatment.
Lactation: Abiplatin is excreted in breast milk. Patients treated with cisplatin must not breas feed.

Caution is essential in order to prevent an inadvertent overdose. An acute overdose of cisplatin may result in renal failure, liver failure, deafness, ocular toxicity (including detachment of the retina), significant myelosuppression, untreatable nausea and vomiting and/or neuritis. In case of overdose (≥200 mg/m2), direct effects on the respiratory centre are possible, which might result in life threatening respiratory disorders and acid-base equilibrium disturbance due to passage of the blood brain barrier.
An overdose may be fatal. There is no specific antidote in the event of an overdose of cisplatin. Even if haemodialysis is initiated 4 hours after the overdose it has little effect on the elimination of cisplatin from the body following a strong and rapid fixation of cisplatin to proteins. Efficient hydration and osmotic diuresis can aid in reduction of toxicity, provided this is applied immediately after overdose. Treatment in the event of an overdose consists of general support measures.