Paraplatin Special Precautions

Attention: Carboplatin is very hemotoxic and may only be used with the greatest care.
Hepatic and renal function; neurological symptoms: A full blood count, tests of kidney and liver function as well as checks of the neurologic status (see Adverse Reactions) should be performed regularly.
The treatment should be discontinued in the case of marked myelosuppression or severe renal or hepatic disorders (see Contraindications).
The creatinine clearance is the most sensitive parameter for the determination of the renal function in patients who are treated with PARAPLATIN and it is useful in order to correlate the excretion of the medicine with myelosuppression. The creatinine clearance is reduced during therapy in 27% of the patients who have a creatinine clearance of ≥60 mL/min at the start of treatment.
In the case of advanced renal insufficiency, the dosage and dosage interval must be adjusted to the glomerular filtration rate (see also Impaired Renal Function under Dosage & Administration).
Cases of Posterior Reversible Encephalopathy Syndrome (PRES) have been reported in patients receiving carboplatin, in most cases as part of combined chemotherapy. PRES is a rare, rapidly developing neurological disease that can include seizures, hypertension, confusion, blindness, and other visual and neurological disorders (see Adverse Reactions). PRES is usually reversible after discontinuation of treatment. The diagnosis of PRES is based on confirmation by imaging techniques, preferably MRI (magnetic resonance imaging).
Hematotoxicity: Myelosuppression is dose-dependent and dose-limiting. Myelosuppression resulting from monotherapy with PARAPLATIN at the recommended dosage is reversible and not cumulative. It may be particularly pronounced in patients with renal insufficiency, in patients who have received an intensive myelosuppressive treatment or cisplatin, as well as in persons whose general state of health is impaired. The initial doses in these patients should therefore be reduced (see also Dosage & Administration). Should suppression occur during the treatment with PARAPLATIN, peripheral blood analyses should be made frequently until recovery. The median of the nadir is 21 days in the case of patients who are treated with PARAPLATIN only and it is 15 days in patients who receive PARAPLATIN in combination. Within 28 days, the platelet count in 90% of patients rises again to over 100,000/mm³, the neutrophil count to over 2,000/mm³ in 74% of the patients and the leukocytes to over 4,000/mm³ in 67% of the patients. The preparation should not be re-administered until the leukocytes, granulocytes and platelets have returned to normal.
Hemolytic anemia with existing drug-induced serological antibodies has been reported in patients treated with carboplatin. This event can be fatal. In case of unexplained hemolysis, serological testing and discontinuation of treatment should be considered (see Adverse Reactions).
Ototoxicity: Auditory defects have been reported during carboplatin therapy. Ototoxicity may be more pronounced in children. Younger age, higher cumulative dose of chemotherapy, carboplatin conditioning for HCT, CNS tumors, renal insufficiency, and concomitant administration of other ototoxic drugs (e.g. aminoglycosides), radiation involving the ear ≥30 Gy or CNS radiation are considered as risk factors. Cases of hearing loss with a delayed onset have been reported in paediatric patients. A hearing test before starting treatment and a long-term audiometric follow-up with yearly (or if hearing loss is detected, more frequently) hearing tests is recommended in this population.
Electrolytes: There have been reports concerning early hyponatremia. The possibility of hyponatremia should not be ignored especially in patients with risk factors such as e.g. a concomitant diuretic therapy. The sodium levels could generally be normalised again by sodium replacement or by limiting water available.
Injection site reactions: Injection site reactions may occur during the administration of PARAPLATIN. Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during drug administration. A specific treatment for extravasation reactions is unknown at this time.
Vaccinations: Concomitant use of PARAPLATIN with a live vaccine may potentiate the replication of the vaccine pathogen and/or may increase the adverse reaction of the vaccine pathogen because normal defense mechanisms may be suppressed by PARAPLATIN. Vaccination with a live vaccine in a patient being treated with PARAPLATIN may result in severe infection. The patient's antibody response to vaccines may be decreased. The use of live vaccines should be avoided and specialist advice should be sought. Killed or inactivated vaccines may be used, however, the response to such vaccines could be reduced (see Interactions).
Effects on Ability to Drive and Use Machines: There is no data available on the effects of PARAPLATIN on driving or using machines. Care should be taken when driving vehicles and operating machines, since undesirable effects such as sight impairment, vomiting and nausea may occur during the course of treatment.