Drugs List

Therapeutic Indications

Uses

Small cell lung cancer
Treatment of carcinoma of the ovary

Ovarian carcinoma of epithelial origin as first line therapy or second line therapy after other treatments have failed.

Small cell carcinoma of the lung.

Unlicensed Uses

Paediatric malignancies

In paediatric patients:
Germ cell tumours, high risk Wilms' tumour, low-grade gliomas, neuroectodermal tumours, retinoblastoma, rhabdomyosarcoma (metastatic and non-metastatic disease), soft-tissue sarcomas, stage 4 neuroblastoma and some liver tumours.

Administration

Dilute and administer by intravenous infusion.

Contraindications

Breastfeeding
Neoplasm with increased bleeding risk
Pregnancy
Renal impairment - creatinine clearance below 20ml/minute
Severe myelosuppression

Precautions and Warnings

Children under 18 years
Patients over 65 years
Dehydration
Hepatic impairment
Renal impairment - creatinine clearance below 60ml/minute

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
For intravenous use only
May interact with aluminium metal - avoid contact with aluminium hardware
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Perform blood counts before and at weekly intervals during treatment
Assess hearing regularly
Monitor for signs and symptoms of allergic reaction
Monitor for signs of neurological toxicity
Monitor for signs of portal hypertension
Monitor hepatic function regularly
Monitor patients for signs of tumour lysis syndrome
Monitor renal function regularly
Monitor serum electrolytes in patients with renal impairment
Antibody response to non-live vaccines may be diminished
Consider the use of anti-emetics before and during therapy
Consider dose reduction/ discontinuation if moderate hepatic changes occur
Discontinue at first signs of microangiopathic haemolytic anaemia
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue or reduce dose if renal impairment worsens
Suspend treatment if neutrophil count is less than 2,000 per cubic mm
Suspend treatment if platelet count is less than 100,000 per cubic mm
Combination myelosuppressive drug therapy may necessitate dose adjustment
Treatment courses should not be repeated more frequently than every 4 weeks
Male & female: Contraception required during & for 6 months after treatment

Myelosuppression is the dose limiting toxic reaction of carboplatin, it is closely related to the renal clearance of the drug. In patients with impaired renal function or who are receiving concomitant therapy with nephrotoxic drugs, myelosuppression, especially thrombocytopenia, may be more severe and prolonged. Initial dose should be reduced by 20 to 25% in patients with risk factors such as myelosuppressive therapy and/or poor performance status (e.g. ECOG-Zubrod performance status of 2-4 or Karnofsky performance status below 80).

Elderly patients with combination therapy of carboplatin and cyclophosphamide, are more likely to develop severe thrombocytopenia than younger patients. Consider renal function when determining dose in this population.

Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

Pregnancy and Lactation

Pregnancy

Carboplatin is contraindicated during pregnancy.

It is not known if carboplatin crosses the placenta, but due to the potential for serious adverse reactions the manufacturer recommends that carboplatin is not used during pregnancy.

Animal studies have shown reproductive toxicity, and has shown dose-related embryo toxicity and teratogenicity in one animal species.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Carboplatin is contraindicated in breastfeeding.

It is not known if carboplatin is excreted in human breast milk. The manufacturer recommends that carboplatin is not used during breastfeeding.

Lactmed suggests that it may be possible for a woman treated with carboplatin to breastfeed safely during intermittent therapy by using an appropriate period of breastfeeding abstinence, but did not suggest a duration for this period.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Allergic reaction
Alopecia
Anaemia
Anaphylactic shock
Anaphylactoid reaction
Anaphylaxis
Angioedema
Anorexia
Asthenia
Blood urea increased
Bronchospasm
Cardiac failure
Cardiovascular disturbances
Cerebrovascular accident
Cerebrovascular disorders
Chest tightness
Chills
Constipation
Decrease in creatinine clearance
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dyspnoea
Electrolyte disturbances
Embolism
Erythema
Erythema at injection site
Erythematous rash
Facial flushing
Facial oedema
Febrile neutropenia
Fever
Haemolytic uraemic syndrome
Haemorrhage
Hearing disturbances
Hearing loss
Hypertension
Hypotension
Impaired fertility
Increase in alkaline phosphatase
Increase in aminotransferase level
Increase in blood urea nitrogen
Increased uric acid level
Infections
Influenza-like syndrome
Injection site reactions
Interstitial lung disease
Leukopenia
Local reaction at injection site
Loss of deep tendon reflexes
Loss of vision(transient)
Malaise
Mucositis
Musculoskeletal disturbances
Myelosuppression
Nausea
Necrosis (injection site)
Nervous system effects
Neutropenia
Optic neuritis
Ototoxicity
Pain
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pneumonia
Pruritus
Pulmonary fibrosis
Rash
Reduced granulocyte count
Renal impairment
Renal toxicity
Respiratory disorders
Reversible posterior leucoencephalopathy syndrome (RPLS)
Risk of secondary tumours as late sequelae
Sensory disturbances
Serum bilirubin increased
Serum creatinine increased
Severe hepatic reactions
Stomatitis
Swelling (injection site)
Tachycardia
Taste disturbances
Thoracic and mediastinal disorders
Thrombocytopenia
Tinnitus
Tumour lysis syndrome
Urticaria
Visual disturbances
Vomiting
Wheezing

Presentation

Parenteral formulations of carboplatin.

Drugs List

Therapeutic Indications

Uses

Small cell lung cancer
Treatment of carcinoma of the ovary

Ovarian carcinoma of epithelial origin as first line therapy or second line therapy after other treatments have failed.

Small cell carcinoma of the lung.

Unlicensed Uses

Paediatric malignancies

In paediatric patients:
Germ cell tumours, high risk Wilms' tumour, low-grade gliomas, neuroectodermal tumours, retinoblastoma, rhabdomyosarcoma (metastatic and non-metastatic disease), soft-tissue sarcomas, stage 4 neuroblastoma and some liver tumours.

Dosage

Local cancer network protocols for the relevant indication should be consulted.

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Patients with Renal Impairment

Administration

Dilute and administer by intravenous infusion.

Contraindications

Breastfeeding
Neoplasm with increased bleeding risk
Pregnancy
Renal impairment - creatinine clearance below 20ml/minute
Severe myelosuppression

Precautions and Warnings

Children under 18 years
Patients over 65 years
Dehydration
Hepatic impairment
Renal impairment - creatinine clearance below 60ml/minute

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
For intravenous use only
May interact with aluminium metal - avoid contact with aluminium hardware
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Perform blood counts before and at weekly intervals during treatment
Assess hearing regularly
Monitor for signs and symptoms of allergic reaction
Monitor for signs of neurological toxicity
Monitor for signs of portal hypertension
Monitor hepatic function regularly
Monitor patients for signs of tumour lysis syndrome
Monitor renal function regularly
Monitor serum electrolytes in patients with renal impairment
Antibody response to non-live vaccines may be diminished
Consider the use of anti-emetics before and during therapy
Consider dose reduction/ discontinuation if moderate hepatic changes occur
Discontinue at first signs of microangiopathic haemolytic anaemia
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue or reduce dose if renal impairment worsens
Suspend treatment if neutrophil count is less than 2,000 per cubic mm
Suspend treatment if platelet count is less than 100,000 per cubic mm
Combination myelosuppressive drug therapy may necessitate dose adjustment
Treatment courses should not be repeated more frequently than every 4 weeks
Male & female: Contraception required during & for 6 months after treatment

Myelosuppression is the dose limiting toxic reaction of carboplatin, it is closely related to the renal clearance of the drug. In patients with impaired renal function or who are receiving concomitant therapy with nephrotoxic drugs, myelosuppression, especially thrombocytopenia, may be more severe and prolonged. Initial dose should be reduced by 20 to 25% in patients with risk factors such as myelosuppressive therapy and/or poor performance status (e.g. ECOG-Zubrod performance status of 2-4 or Karnofsky performance status below 80).

Elderly patients with combination therapy of carboplatin and cyclophosphamide, are more likely to develop severe thrombocytopenia than younger patients. Consider renal function when determining dose in this population.

Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

Pregnancy and Lactation

Pregnancy

Carboplatin is contraindicated during pregnancy.

It is not known if carboplatin crosses the placenta, but due to the potential for serious adverse reactions the manufacturer recommends that carboplatin is not used during pregnancy.

Animal studies have shown reproductive toxicity, and has shown dose-related embryo toxicity and teratogenicity in one animal species.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Carboplatin is contraindicated in breastfeeding.

It is not known if carboplatin is excreted in human breast milk. The manufacturer recommends that carboplatin is not used during breastfeeding.

Lactmed suggests that it may be possible for a woman treated with carboplatin to breastfeed safely during intermittent therapy by using an appropriate period of breastfeeding abstinence, but did not suggest a duration for this period.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Allergic reaction
Alopecia
Anaemia
Anaphylactic shock
Anaphylactoid reaction
Anaphylaxis
Angioedema
Anorexia
Asthenia
Blood urea increased
Bronchospasm
Cardiac failure
Cardiovascular disturbances
Cerebrovascular accident
Cerebrovascular disorders
Chest tightness
Chills
Constipation
Decrease in creatinine clearance
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dyspnoea
Electrolyte disturbances
Embolism
Erythema
Erythema at injection site
Erythematous rash
Facial flushing
Facial oedema
Febrile neutropenia
Fever
Haemolytic uraemic syndrome
Haemorrhage
Hearing disturbances
Hearing loss
Hypertension
Hypotension
Impaired fertility
Increase in alkaline phosphatase
Increase in aminotransferase level
Increase in blood urea nitrogen
Increased uric acid level
Infections
Influenza-like syndrome
Injection site reactions
Interstitial lung disease
Leukopenia
Local reaction at injection site
Loss of deep tendon reflexes
Loss of vision(transient)
Malaise
Mucositis
Musculoskeletal disturbances
Myelosuppression
Nausea
Necrosis (injection site)
Nervous system effects
Neutropenia
Optic neuritis
Ototoxicity
Pain
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pneumonia
Pruritus
Pulmonary fibrosis
Rash
Reduced granulocyte count
Renal impairment
Renal toxicity
Respiratory disorders
Reversible posterior leucoencephalopathy syndrome (RPLS)
Risk of secondary tumours as late sequelae
Sensory disturbances
Serum bilirubin increased
Serum creatinine increased
Severe hepatic reactions
Stomatitis
Swelling (injection site)
Tachycardia
Taste disturbances
Thoracic and mediastinal disorders
Thrombocytopenia
Tinnitus
Tumour lysis syndrome
Urticaria
Visual disturbances
Vomiting
Wheezing

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2018

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Carboplatin 10mg/ml concentration for solution for infusion. Accord Healthcare Ltd. Revised November 2012.
Summary of Product Characteristics: Carboplatin 10mg/ml concentration for solution for infusion. Hospira UK Ltd. Revised May 2017.
Summary of Product Characteristics: Carboplatin 10mg/ml concentration for solution for infusion. Teva UK Ltd. Revised February 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 19th July 2018