Carboplatin

Registered South African indications:

• Advanced ovarian carcinoma
• Small cell carcinoma of the lung

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• History of severe allergic reaction to carboplatin or other platinum containing compounds
• Severe renal impairment (CrCl <30ml/min) unless in the judgment of the physician and patient, the possible benefits of treatment outweigh the risks
• Severe myelosuppression
• Bleeding tumours
• Coadministration with the yellow fever vaccine

Cautions  

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment
• Hepatic impairment
• Elderly
• Male patients of reproductive age
• Previous extensive carboplatin treatment
• Previous extensive cisplatin treatment
• Risk factors for tumour lysis syndrome
  - High proliferative rate
  - High tumour burden
  - High sensitivity to cytotoxic agents
• Aluminium containing equipment and administration sets (See additional prescribing points)
• Glomerular Filtration Rate estimation using Cockroft Gault Formula in:
  - Age: 40-59 years
  - BMI: 20-25
• Children
• Coadministration with nephrotoxic agents
• Coadministration with live vaccines (See additional prescribing points)
• Coadministration with anticoagulative treatment (See additional prescribing points)
• Coadministration with chemotherapy
• May impair ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: inj

Used for the treatment of

• Ovarian carcinoma of epithelial origin
• Small cell lung carcinoma 

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy 

• Caution; positive evidence of risk
• Carboplatin can cause foetal harm when administered to a pregnant woman. Carboplatin has been shown to be embryo toxic and teratogenic in rats receiving the drug during organogenesis. No controlled studies in pregnant women have been conducted
• Safe use of carboplatin 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 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

Breastfeeding 

• Caution; not recommended
• It is not known whether carboplatin is excreted in breast milk
• To avoid possible harmful effects in the infant, breastfeeding must be stopped during carboplatin therapy  

Fertility

• Gonadal suppression resulting in amenorrhoea or azoospermia 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 therapy because of the possibility of irreversible infertility due to therapy with carboplatin

Renal Impairment

• Mild to moderate: Caution; dose adjustment recommended 
• Dosage of carboplatin should be reduced (refer to Calvert formula) and haematological nadirs and renal function monitored
  Patients with creatinine clearance values <60ml/min are at increased risk of severe myelosuppression
  The above dosing recommendation applies to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance and to the acceptable level of myelosuppression
• Severe: Contraindicated
  Contraindicated in patients with pre-existing severe renal impairment (with CrCl <30ml/min) unless in the judgement of the physician and patients, the possible benefits of treatment outweigh the risks

Hepatic Impairment 

• Caution; no dose adjustment recommended 

Elderly 

• Caution; dose adjustment recommended
  In patients >65 years, adjustment of the carboplatin dose to the general condition is necessary during the first and subsequent therapeutic courses
  In studies involving combination therapy with carboplatin and cyclophosphamide, elderly patients treated with carboplatin were more likely to develop severe thrombocytopenia than younger patients. Because renal function is often decreased in the elderly, renal function should be considered when determining dosage

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Peripheral neuropathy
• Paraesthesia
• Decreased osteotendinous reflexes
• Cerebrovascular accident
• Encephalopathy
• Reversible Posterior Leukoencephalopathy Syndrome
  - Seizure
  - Hypertension
  - Headache
  - Confusion
  - Blindness
  - Other visual and neurological disturbances
• Asthenia

Cardiovascular Disorders 

• Cardiac failure
• Embolism
• Hypertension
• Hypotension
• Venocculusive disease (sinusoidal obstruction syndrome) (including fatal outcomes)
  - Abnormal liver function
  - Portal hypertension not resulting from liver metastases

Respiratory Disorders 

• Pneumonia
• Interstitial lung disease
• Bronchospasm
• Pulmonary fibrosis
  - Tightness of the chest
  - Dyspnoea

Gastrointestinal Disorders 

• Nausea and vomiting
• Abdominal pain
• Diarrhoea
• Constipation
• Mucous membrane disorder
• Stomatitis
• Pancreatitis

Hepatobiliary Disorders 

• Increased blood alkaline phosphatase
• Increased aspartate aminotransferase
• Abnormal liver function tests
• Increased bilirubin
• Acute, fulminant liver cell necrosis (high-dose administration)

Genitourinary Disorders 

• Renal toxicity
• Increased uric acid
• Increased blood urea
• Increased serum creatinine
• Decreased creatinine clearance

Endocrine and Metabolic Disorders 

• Dehydration
• Anorexia
• Hyponatraemia
• Tumour lysis syndrome
• Decreased sodium
• Decreased potassium
• Decreased calcium
• Decreased magnesium

Skin and Subcutaneous Tissue Disorders 

• Alopecia
• Urticaria
• Erythema
• Pruritis
• Injection site reactions
  - Injection site necrosis
  - Injection site extravasation
  - Injection site erythema

Immune, Blood and Lymphatic System Disorders

• Treatment related secondary malignancy
• Infections (including fatal outcomes)
• Thrombocytopenia
• Leukopenia
• Neutropenia
• Anaemia
• Haemorrhage (including fatal outcome)
• Bone marrow failure
• Febrile neutropenia
• Haemolytic-uraemic syndrome
  - Rapidly decreasing haemoglobin
  - Concomitant thrombocytopenia
  - Increased bilirubin
  - Increased creatinine
  - Increased blood urea nitrogen
  - Increased lactate dehydrogenase
• Haemolytic anaemia
• Hypersensitivity
• Anaphylactoid type reaction
  - Facial oedema
  - Dyspnoea
  - Tachycardia
  - Low blood pressure
  - Urticaria
  - Anaphylactic shock
  - Bronchospasm
• Fever
• Chills

Sensory Disorders

• Dysgeusia
• Visual disturbance
• Loss of vision (rare)
• Ototoxicity
• Hypoacusia
• Subclinical decrease in hearing acuity

• Oral anticoagulants
• Yellow fever vaccine
• Live attenuated vaccines
• Phenytoin
• Fosphenytoin
• Ciclosporin
• Tacrolimus
• Sirolimus
• Nephrotoxic agents
• Ototoxic agents
• Aminoglycosides
• Vancomycin
• Capreomycin
• Diuretics
• Loop diuretics
• Myelosuppressive agents

Other

• Aluminium (See additional prescribing points)

• Renal function
• Hepatic function
• Full blood count
• Electrolytes
• Hepatitis B screening

Specific cases may require:

• Audiology evaluations
• Neurological examination
• International Normalised Ratio (INR)

Additional observations

• Signs and symptoms of hypersensitivity reactions

Frequency of therapy

• Carboplatin courses should not, in general, be repeated more frequently than every 4 weeks in order to ensure that the nadir in blood counts has occurred and there has been recovery to a satisfactory level

Interaction with aluminium

• Carboplatin may interact with aluminium to form a black precipitate
• Needles, syringes, catheters or IV administration sets that contain aluminium parts which may come into contact with carboplatin should not be used for the preparation or administration of the drug

Coadministration with live vaccines

• Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including carboplatin may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving carboplatin
• Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished

Coadministration with anticoagulant treatment

• Due to the increase of thrombotic risk in cases of tumoral diseases, the use of anticoagulative treatment is frequent
• The high intra-individual variability of the coagulability during diseases, and the possibility of interaction between oral anticoagulants and anticancer chemotherapy, may require an increase in frequency of INR monitoring if a patient is treated with oral anticoagulants

Carboplatin, like Cisplatin, interferes with DNA intra-strand and inter-strand crosslinks in cells exposed to the drug. DNA reactivity has been correlated with cytotoxicity.

Injection (per ml) 10mg

• Accord-Carboplatin (Accord)
• Aspen carboplatin (Pharmacare)
• Carbosin 10 (Teva Pharmaceuticals)

Injection (per 15ml) 150mg

• Abic carboplatin (Pharmachemie)
• Accord Carboplatin (Accord)
• Aspen Carboplatin (Pharmacare)
• Carboplatin 150mg/15ml Fresenius (Fresenius Kabi SA)
• Carbosin 150 (Teva Pharmaceuticals)
• Paraplatin rtu (Bristol-Myers)
• P&U carboplatin CSV (Pfizer) (Originator)

Injection (per 45ml) 450mg

• Abic carboplatin (Pharmachemie)
• Accord Carboplatin (Accord)
• Aspen Carboplatin (Pharmacare)
• Carboplatin 450mg/45ml Fresenius (Fresenius Kabi SA)
• Carbosin 450 (Teva Pharmaceuticals)
• Paraplatin rtu (Bristol-Myers)
• P&U carboplatin CSV (Pfizer) (Originator)

Injection (per 60ml) 600mg

• Carboplatin 600mg/60ml Fresenius (Fresenius Kabi SA)
• Carbosin 600 (Teva Pharmaceuticals)