Gemcitabine parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions containing gemcitabine hydrochloride.
Drugs List
Therapeutic Indications
Uses
Advanced bladder cancer: combination with cisplatin
Advanced ovarian carcinoma - combination with carboplatin
Locally advanced or metastatic adenocarcinoma of pancreas
Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
Metastatic breast cancer where anthracycline therapy has failed
First line treatment of locally advanced or metastatic non-small cell lung cancer in combination with cisplatin. Monotherapy can be considered in the elderly or patients with performance status 2.
Treatment of locally advanced or metastatic adenocarcinoma of the pancreas.
Treatment of locally advanced or metastatic bladder cancer, in combination with cisplatin.
Treatment of unresectable, locally recurrent or metastatic breast cancer in combination with paclitaxel, for relapsed patients, following adjuvant/neo-adjuvant chemotherapy. Unless clinically contraindicated, prior chemotherapy should have included an anthracycline.
Treatment of locally advanced or metastatic epithelial ovarian carcinoma, in combination with carboplatin, in patients with relapsed disease following a recurrence-free interval of at least 6 months after platinum based first-line therapy.
Dosage
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.
Additional Dosage Information
Non-haematological toxicity
Grade 3 or 4 non-haematological toxicity, except nausea/vomiting: Suspend treatment or reduce dose until symptoms resolve.
Haematological toxicity
All indications
Prior to each treatment cycle with gemcitabine patients should have an absolute granulocyte count of at least 1.5 x 10 to the power of 9/L and platelet count of 100 x 10 to the power of 9/L.
Dose modification for bladder cancer, NSCLC and pancreatic cancer within a cycle (mono- or cisplatin combination therapy)
Absolute granulocyte count greater than 1 x 10 to the power of 9/L and platelet count greater than 100 x 10 to the power of 9/L: Dose as normal.
Absolute granulocyte count between 0.5 and 1 x 10 to the power of 9/L and/or platelet count between 50 and 100 x 10 to the power of 9/L: 75% of full dose.
Absolute granulocyte count less than 0.5 x 10 to the power of 9/L and/or platelet count less than 50 x 10 to the power of 9/L: Suspend treatment.
Treatment may be reinstated within a cycle provided the absolute granulocyte count is above 0.5 x 10 to the power of 9/L and the platelet count is above 50 x 10 to the power of 9/L.
Dose modification in breast cancer within cycle (combination with paclitaxel)
Absolute granulocyte count equal to or greater than 1.2 x 10 to the power of 9/L and platelet count greater than 75 x 10 to the power of 9/L: Dose as normal.
Absolute granulocyte count between 1 and 1.2 x 10 to the power of 9/L and/or platelet count between 50 and 75 x 10 to the power of 9/L: 75% of full dose.
Absolute granulocyte count between 0.7 and 1 x 10 to the power of 9/L and platelet count equal to or greater than 50 x 10 to the power of 9/L: 50% of full dose.
Absolute granulocyte count less than 0.7 x 10 to the power of 9/L and/or platelet count less than 50 x 10 to the power of 9/L: Suspend treatment until next cycle.
Treatment may be reinstated on day one of the next cycle provided the absolute granulocyte count is above 1.5 x 10 to the power of 9/L and the platelet count is above 100 x 10 to the power of 9/L.
Dose modification in ovarian cancer within cycle (combination with carboplatin)
Absolute granulocyte count greater than 1.5 x 10 to the power of 9/L and platelet count greater than 100 x 10 to the power of 9/L: Dose as normal.
Absolute granulocyte count between 1 and 1.5 x 10 to the power of 9/L and/or platelet count between 75 and 100 x 10 to the power of 9/L: 50% of full dose.
Absolute granulocyte count less than 1 x 10 to the power of 9/L and/or platelet count less than 75 x 10 to the power of 9/L: Suspend treatment until next cycle.
Treatment may be reinstated on day one of the next cycle provided the absolute granulocyte count is above 1.5 x 10 to the power of 9/L and the platelet count is above 100 x 10 to the power of 9/L.
Dose modifications due to haematological toxicity in subsequent cycles
The gemcitabine dose should be reduced to 75% of the original dose if any of the following occur:
Absolute granulocyte count less than 0.5 x 10 to the power of 9/L for more than 5 days.
Absolute granulocyte count less than 0.1 x 10 to the power of 9/L for more than 3 days.
Febrile neutropenia.
Platelets less than 25 x 10 to the power of 9/L.
Cycle delay of more than 1 week due to toxicity.
Administration
For intravenous infusion.
Contraindications
Children under 18 years
Granulocyte count less than 1.5 x 10 to the power 9/ L at baseline
Platelet count below 100 x 10 to the power of 9 / L at baseline
Breastfeeding
Pregnancy
Precautions and Warnings
Concurrent radiotherapy
Restricted sodium intake
Alcoholism
Hepatic cirrhosis
Hepatic impairment
Hepatic metastases
Hepatitis
History of cardiovascular disorder
Myelosuppression
Renal impairment
Administration of live vaccines is not recommended
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be initiated and supervised by a specialist
Some formulations contain propylene glycol
Some formulations may contain alcohol
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor closely patient at risk of cardiovascular disorders
Monitor closely patient with pre-existing hepatic impairment
Monitor for symptoms of Capillary Leak Syndrome
Monitor hepatic function regularly
Monitor platelets, leucocytes and granulocytes before each dose
Monitor renal function regularly
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report headaches, seizures, confusion, visual disturbance
Consider discontinuing if pulmonary function becomes impaired
Discontinue at first signs of microangiopathic haemolytic anaemia
Discontinue if patient shows signs of capillary leak syndrome
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Suspend or modify if drug-induced bone marrow depression is detected
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Female: Ensure adequate contraception during treatment
Male: Contraception required during and for 6 months after treatment
Breastfeeding: Do not breastfeed & discard milk for 1 week after therapy
Gemcitabine should be discontinued at the first signs or evidence of microangiopathic haemolytic anaemia, including rapidly falling haemoglobin with concomitant thrombocytopenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen or lactate dehydrogenase.
Gemcitabine has been shown to have radio-sensitising activity. Significant toxicity including severe and potentially life-threatening mucositis, oesophagitis and pneumonitis has been observed when administered concurrently (given together or within 7 days of each other) with therapeutic thoracic radiation in non-small cell lung cancer patients.
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
Gemcitabine is contraindicated during pregnancy.
At the time of writing there is limited data on the use of gemcitabine in human pregnancy. Animal studies have shown reproductive toxicity at a fraction (1/200th) of the human dose, including birth defects, embryonic and foetal developmental defects and defects in the course of gestation, perinatal and postnatal development.
The effect of concurrent therapies must also be considered.
Lactation
Gemcitabine is contraindicated during breastfeeding.
It is unknown if gemcitabine is excreted in human milk therefore a risk to neonates cannot be excluded. Sources recommend withholding from breastfeeding for 7 days after gemcitabine administration.
The effect of concurrent therapies must also be considered.
Side Effects
Adult respiratory distress syndrome
Alopecia
Anaemia
Anaphylactoid reaction
Anorexia
Arrhythmias
Asthenia
Back pain
Bronchospasm
Bullous eruption
Capillary leak syndrome
Cardiac failure
Cerebrovascular accident
Chills
Constipation
Cough
Desquamation
Diarrhoea
Dyspnoea
Facial oedema
Fatigue
Febrile neutropenia
Fever
Gamma glutamyl transferase (GGT) increased
Gangrene
Granulocytopenia
Haematuria
Haemolytic uraemic syndrome
Haemorrhage
Headache
Hepatic failure
Hepatotoxicity
Hypotension
Increase in alkaline phosphatase
Increase in ALT level
Increase in AST level
Increased susceptibility to infection
Influenza-like syndrome
Injection site reactions
Insomnia
Interstitial pneumonitis
Ischaemic colitis
Itching
Leucopenia
Malaise
Mouth ulcers
Myalgia
Myelosuppression
Myocardial infarction
Nausea
Neuropathy
Neutropenia
Oedema
Peripheral oedema
Posterior reversible encephalopathy syndrome (PRES)
Proteinuria
Pruritus
Pulmonary oedema
Radiation recall dermatitis
Rash
Renal failure
Rhinitis
Scaling of skin
Sepsis
Serum bilirubin increased
Skin ulcer
Somnolence
Stevens-Johnson syndrome
Stomatitis
Supraventricular arrhythmias
Sweating
Thrombocytopenia
Thrombocytosis
Thrombotic microangiopathy
Toxic epidermal necrolysis
Vasculitis
Vesiculation
Vomiting
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: March 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
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.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Gemcitabine 100mg/ml concentrate for solution for infusion. Accord Healthcare Limited. Revised August 2012.
Summary of Product Characteristics: Gemcitabine 200 mg powder for solution for infusion. Accord Healthcare Limited. Revised March 2017.
Summary of Product Characteristics: Gemcitabine 1 g powder for solution for infusion. Accord Healthcare Limited. Revised March 2017.
Summary of Product Characteristics: Gemcitabine 2 g powder for solution for infusion. Accord Healthcare Limited. Revised March 2017.
Summary of Product Characteristics: Gemcitabine 40 mg/ml concentrate for solution for infusion. Accord UK Ltd. Revised April 2017.
Summary of Product Characteristics: Gemcitabine 38 mg/ml concentrate for solution for infusion. Fresenius Kabi. Revised December 2014.
Summary of Product Characteristics: Gemcitabine 10 mg/ml solution for infusion. Ranbaxy (UK) Limited a Sun Pharmaceutical Company. Revised February 2019.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Gemcitabine Last revised: 03 December 2018
Last accessed: 15 March 2019
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