Chemical formula: C₆H₁₂N₂O₄Pt Molecular mass: 371.254 g/mol PubChem compound: 38904
Carboplatin interacts in the following cases:
Live attenuated vaccines (except yellow fever) with carboplatin: Risk of systemic, possible fatal disease. This is increased in subjects who are already immunosuppressed by their underlying disease. Use inactivated vaccine where this exist (poliomyelitis). Concomitant use not recommended.
The concomitant use of carboplatin with loop diuretic should be approached with caution due to the cumulative nephrotoxicity and ototoxicity.
Concurrent therapy with nephrotoxic drugs or ototoxic drugs such as amino glycosides, vancomycin, capreomycin and diuretics, may increase or exacerbate toxicity, particularly in renal failure patients, due to carboplatin induced changes in renal clearance.
Gonadal suppression resulting in amenorrhoea or azospermia may occur in patients receiving antineoplastic therapy. These effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian functional impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents.
Men of sexually mature age treated with carboplatin are advised not to father a child during treatment and up to 6 months afterwards. Male patients should seek advice about sperm preservation prior to initiation of the therapy because of the possibility of irreversible infertility due to therapy with carboplatin.
Ciclosporin (and by extrapolation tacrolimus and sirolimus) with carboplatin: Excessive immunosuppression with risk of lymphoproliferation.
Phenytoin, fosphenytoin with carboplatin: Risk of exacerbation of convulsions (resulting from the decrease of phenytoin digestive absorption by the cytotoxic drug), risk of toxicity enhancement or loss of efficacy of the cytotoxic drug (due to increased hepatic metabolism by phenytoin). Concomitant use not recommended.
Carboplatin may interact with aluminium to form a black precipitate. Needles, syringes, catheters or intravenous sets containing aluminium parts that may come into contact with carboplatin should not be used for preparation or administration of carboplatin. Precipitation can lead to a reduction of the antineoplastic activity.
Carboplatin can cause foetal harm when administered to a pregnant woman. Carboplatin has been shown to be embryotoxic and teratogenic in rats receiving the drug during organogenesis. No controlled studies in pregnant women have been conducted.
Safe use of carboplatin in pregnancy has not been established. Both men and women receiving carboplatin should be informed of the potential risk of adverse effects on reproduction. Women of childbearing potential should be advised to avoid becoming pregnant by using effective contraception and should be fully informed of the potential hazard to the foetus should they become pregnant during carboplatin therapy. Carboplatin should not be used in pregnant women or women of childbearing potential who might become pregnant unless the potential benefits to the mother outweigh the possible risks to the foetus.
It is not known whether carboplatin is excreted in breast milk.
To avoid possible harmful effects in the infant, breast-feeding must be stopped during carboplatin therapy.
Gonadal suppression resulting in amenorrhoea or azospermia may occur in patients receiving antineoplastic therapy. These effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian functional impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents.
Men of sexually mature age treated with carboplatin are advised not to father a child during treatment and up to 6 months afterwards. Male patients should seek advice about sperm preservation prior to initiation of the therapy because of the possibility of irreversible infertility due to therapy with carboplatin.
No studies of the effects on the ability to drive and use machines have been performed. However, carboplatin may cause nausea, vomiting, vision abnormalities and ototoxicity; therefore, patients should be warned of the potential effect of these events on the ability to drive or to use machines.
The frequency of adverse reactions reported is based on a cumulative database of 1,893 patients receiving single agent carboplatin injection and post-marketing experience.
The list is presented by system organ class, MedDRA preferred term, and frequency using the following frequency categories: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, ≤1/100), rare (≥1/10,000, ≤1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data)
Not known: Treatment related secondary malignancy
Common: Infections*
Not known: Pneumonia
Very common: Thrombocytopenia, neutropenia, leukopenia, anaemia
Common: Haemorrhage*
Not known: Bone marrow failure, haemolytic-uraemic syndrome
Rare: febrile neutropenia,
Common: Hypersensitivity, anaphylactoid type reaction
Not known: Dehydration, anorexia, Tumor lysis syndrome
Rare: hyponatraemia
Common: Neuropathy peripheral, paraesthesia, decrease of osteotendinous reflexes, sensory disturbance, dysgeusia
Not known: Cerebrovascular accident*, Reversible Posterior Leukoencephalopathy Syndrome (RPLS).
Common: Visual disturbance (incl. rare cases of loss of vision)
Common: Ototoxicity
Common: Cardiovascular disorder*
Not known: Cardiac failure*
Not known: Embolism*, hypertension, hypotension
Common: Respiratory disorder, interstitial lung disease, bronchospasm
Very common: Vomiting, nausea, abdominal pain
Common: Diarrhoea, constipation, mucous membrane disorder
Not known:__ Stomatitis, Pancreatitis.
Common: Alopecia, skin disorder
Not known: Urticaria, rash, erythema, pruritus
Common: Musculoskeletal disorder
Common: Urogenital disorder
Common: Asthenia
Not known: Injection site necrosis, injection site reaction, injection site extravasation, injection site erythema, malaise
Very Common: Creatinine renal clearance decreased, blood urea increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, liver function test abnormal, blood sodium decreased, blood potassium decreased, blood calcium decreased, blood magnesium decreased.
Common: Blood bilirubin increased, blood creatinine increased, blood uric acid increased
* Fatal in <1%, fatal cardiovascular events in <1% included cardiac failure, embolism, and cerebrovascular accident combined.
Myelosuppression is the dose-limiting toxicity of carboplatin injection. In patients with normal baseline values, thrombocytopenia with platelet counts below 50,000/mm³ occurs in 25% of patients, neutropenia with granulocyte counts below 1,000/mm³ in 18% of patients, and leukopenia with WBC counts below 2,000/mm³ in 14% of patients. The nadir usually occurs on day 21. Myelosuppression can be worsened by combination of carboplatin injection with other myelosuppressive compounds or forms of treatment.
Myelotoxicity is more severe in previously treated patients, in particular in patients previously treated with cisplatin and in patients with impaired kidney function. Patients with poor performance status have also experienced increased leukopenia and thrombocytopenia. These effects, although usually reversible, have resulted in infectious and hemorrhagic complications in 4% and 5% of patients given carboplatin injection, respectively. These complications have led to death in less than 1% of patients.
Anaemia with haemoglobin values below 8g/dl has been observed in 15% of patients with normal baseline values. The incidence of anaemia is increased with increasing exposure to carboplatin injection.
Myelosuppression may be more severe and prolonged in patients with impaired renal function, extensive prior treatment, poor performance status and age above 65.
At maximum tolerated dosages of carboplatin administered as a single agent, thrombocytopenia, with nadir platelet counts of less than 50 × 109/l, occurs in about a third of the patients. The nadir usually occurs between days 14 and 21, with recovery within 35 days from the start of therapy.
Leukopenia has also occurred in approximately 20% of patients but its recovery from the day of nadir (day 14-28) may be slower and usually occurs within 42 days from the start of therapy. Neutropenia with granulocyte counts below 1 × 109/l occurs in approximately one fifth of patients. Haemoglobin values below 9.5 mg/100ml have been observed in 48% of patients with normal base-line values.
Secondary acute malignancies after cytostatic combination therapies containing carboplatin have been reported.
Very rare: Pulmonary fibrosis manifested by tightness of the chest and dyspnoea. This should be considered if a pulmonary hypersensitivity state is excluded (see General disorders below).
Vomiting occurs in 65% of patients, in one-third of whom it is severe. Nausea occurs in an additional 15%. Previously treated patients (in particular patients previously treated with cisplatin) appear to be more prone to vomiting. Nausea and vomiting are generally delayed until 6 to 12 hours after administration of carboplatin, are readily controlled or prevented with antiemetic s and disappear within 24hours. Vomiting is more likely when carboplatin injection is given in combination with other emetogenic compounds.
The other gastrointestinal complaints corresponded to pain in 8% of patients, diarrhoea, and constipation in 6% of patients. Cramps have also been reported.
Peripheral neuropathy (mainly paresthesias and decrease of osteotendinous reflexes) has occurred in 4% of patients administered carboplatin injection. Patients older than 65 years and patients previously treated with cisplatin, as well as those receiving prolonged treatment with carboplatin injection, appear to be at increased risk.
Clinically significant-sensory disturbances (ie, visual disturbances and taste modifications) have occurred in 1% of patients.
The overall frequency of neurologic side effects seems to be increased in patients receiving carboplatin injection in combination. This may also be related to longer cumulative exposure. Parasthesias present prior to treatment, especially if caused by cisplatin, may persist or worsen during carboplatin therapy.
Visual disturbances, including sight loss, are usually associated with high dose therapy in renally impaired patients.
Very common: A subclinical decrease in hearing acuity in the high frequency range (4000-8000 Hz), determined by audiogram, occurred in 15% of patients. Very rare cases of hypoacusia have been reported.
Common: Tinnitus was also commonly reported. Hearing loss as a result of cisplatin therapy may give rise to persistent or worsening symptoms. At higher than recommended doses, in common with other ototoxic agents, clinically significant hearing loss has been reported to occur in paediatric patients when carboplatin is administered.
Modification of liver function in patients with normal baseline values was observed, including elevation of total bilirubin in 5%, SGOT in 15%, and alkaline phosphatase in 24% of patients. These modifications were generally mild and reversible in about one-half the patients.
In a limited series of patients receiving very high dosages of carboplatin injection and autologous bone marrow transplantation, severe elevation of liver function tests has occurred.
Cases of an acute, fulminant liver cell necrosis occured after high-dose administration of carboplatin.
When given in usual doses, development of abnormal renal function has been uncommon, despite the fact that carboplatin injection has been administered without high-volume fluid hydration and/or forced diuresis. Elevation of serum creatinine occurs in 6% of patients, elevation of blood urea nitrogen in 14%, and of uric acid in 5% of patients. These are usually mild and are reversible in about one-half the patients. Creatinine clearance has proven to be the most sensitive renal function measure in patients receiving carboplatin injection. Twenty-seven percent (27%) of patients who have a baseline value of 60 mL/min or greater, experience a reduction in creatinine clearance during carboplatin injection therapy. Impairment of renal function is more likely in patients who have previously experienced nephrotoxicity as a result of cisplatin therapy.
Very common: Renal toxicity is usually not dose-limiting in patients receiving carboplatin, nor does it require preventive measures such as high volume fluid hydration or forced diuresis.
Common: Renal function impairment, as defined by a decrease in the creatinine clearance below 60 ml/min.
Anaphylactic-type reactions, sometimes fatal, may occur in the minutes following injection of the product: facial oedema, dyspnoea, tachycardia, low blood pressure, urticaria, anaphylactic shock, bronchospasm.
Fever with no apparent cause has also been reported.
Erythematous rash, fever and pruritis have been observed. These were reactions similar to those seen after cisplatin therapy but in a few cases no cross-reactivity was present.
Decreases in serum sodium, potassium, calcium, and magnesium occur in 29%, 20%, 22%, and 29% of patients, respectively. In particular, cases of early hyponatraemia have been reported. The electrolyte losses are minor and mostly take a course without any clinical symptoms.
Isolated cases of cardiovascular incidents (cardiac insufficiency, embolism) as well as isolated cases of cerebrovascular accidents have been reported.
Reactions at the site of injection (burning, pain, reddening, swelling, urticaria, necrosis in connection with extravasation) have been reported.
Fever, chills and mucositis have occasionally been observed.
Very common: The alkaline phosphatase level is increased more frequently than SGOT, SGPT or total bilirubin The majority of these abnormalities regress spontaneously during the course of treatment.
Rare: Severe hepatic dysfunction (including acute liver necrosis) has been reported after administration of higher than recommended carboplatin dosages.
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