Pemetrexed diarginine parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of pemetrexed diarginine.
Drugs List
Therapeutic Indications
Uses
Advanced/metastatic non-small cell lung cancer as monotherapy
Advanced/metastatic non-small cell lung cancer: combination with cisplatin
Unresectable malignant pleural mesothelioma: in combination with cisplatin
In combination with cisplatin for the treatment of chemotherapy naive patients with unresectable malignant pleural mesothelioma.
In combination with cisplatin for first line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
As monotherapy for maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum based chemotherapy.
As monotherapy for second line treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
In combination with cisplatin:
The recommended dose is 500mg per square metre body surface area administered as an intravenous infusion over 10 minutes on the first day of each 21 day cycle.
The recommended dose of cisplatin is 75mg per square metre body surface area infused over 2 hours approximately 30 minutes after completion of the pemetrexed infusion on the first day of each 21 day cycle.
As monotherapy:
The recommended dose is 500mg per square metre body surface area administered as an intravenous infusion over 10 minutes on the first day of each 21 day cycle.
Additional Dosage Information
Pre-medication regime:
A corticosteroid should be given the day prior to, on the day of and the day after treatment in order to reduce the incidence and severity of skin reactions. The corticosteroid should be equivalent to 4mg dexamethasone administered orally twice a day.
Patients undergoing treatment with pemetrexed should also receive vitamin supplementation in order to reduce toxicity. Patients should take oral folic acid or a multivitamin containing folic acid (350 - 1000 micrograms) on a daily basis. At least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed. Dosing must continue during treatment and for 21 days after the last dose of pemetrexed.
Patients must receive an intramuscular injection of vitamin B12 (1000 micrograms) in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given on the same day as pemetrexed.
Dose adjustments:
Treatment should be discontinued if a patient experiences any haematological or non-haematological grade 3 or 4 toxicity after 2 dose reductions, or immediately if grade 3 or 4 neurotoxicity is observed.
Dosage adjustments at the start of any cycle should be based on nadir haematological counts or maximum non-haematological toxicity from the preceding cycle of therapy.
Treatment may be delayed to allow sufficient time for recovery. Upon recovery, patients should be retreated with pemetrexed at the recommended reduced dosages:
Dose modification for haematological toxicities:
Nadir absolute neutrophil count (ANC) less than 500 per cubic millimetre and nadir platelets equal to or greater than 50,000 per cubic millimetre: Once resolved restart treatment at 75% of previous dose (pemetrexed and cisplatin).
Nadir platelets less than or equal to 50,000 per cubic millimetre (with any ANC): Once resolved restart treatment at 75% of previous dose (pemetrexed and cisplatin).
Nadir platelets less than or equal to 50,000 per cubic millimetre (with bleeding, with any ANC): Once resolved restart treatment at 50% of previous dose (pemetrexed and cisplatin).
Dose modification for non-haematological toxicities (except neurotoxicity):
Patients developing non-haematological toxicities greater than or equal to grade 3 (excluding neurotoxicity) should have treatment withheld until resolution to less than or equal to the patients pre-therapy value. When treatment resumes it should be at the levels listed below:
Any grade 3 or 4 toxicities except mucositis: Once resolved restart treatment at 75% of the previous dose (pemetrexed and cisplatin).
Any diarrhoea requiring hospitalisation or grade 3 or 4 diarrhoea: Once resolved restart treatment at 75% of the previous dose (pemetrexed and cisplatin).
Grade 3 or 4 mucositis: Once resolved restart treatment at 50% of the previous dose of pemetrexed and 100% of the previous dose of cisplatin.
Dose modification for neurotoxicity:
Common toxicity grade 0 to 1: Next dose should be 100% of the previous dose (pemetrexed and cisplatin).
Common toxicity grade 2: Next dose should be 100% of the previous dose of pemetrexed and 50% of the previous dose of cisplatin.
Common toxicity grade 3 to 4: Discontinue therapy.
Administration
For administration by intravenous infusion only.
Contraindications
Children under 18 years
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9 / L at baseline
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 45ml/minute
Precautions and Warnings
Ascites
Concurrent radiotherapy
History of radiotherapy
Risk factors for cardiovascular disorder
Dehydration
Diabetes mellitus
Hypertension
Serum bilirubin above 1.5 times upper limit of normal
Serum transaminases above 3 times upper limit of normal
Significant pleural effusion
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
Patients must receive folic acid and vitamin B12 throughout treatment
Pre-medication with an oral corticosteroid recommended before treatment
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Before each treatment monitor full blood count, renal and hepatic function
Ensure adequate hydration prior to infusion
Reduce dose if platelet count < 50,000 per cubic mm
Consider the use of anti-emetics before and during therapy
Discontinue if grade 3 neurological toxicity occurs
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Suspend treatment if neutrophil count is less than 1,500/cubic mm
Suspend treatment if platelet count is less than 100,000 per cubic mm
Advise patients to avoid aspirin and NSAID use
Female: Ensure adequate contraception during treatment
Male: Contraception required during and for 6 months after treatment
Patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 ml/minute) should avoid taking non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. ibuprofen and aspirin greater than 1.3g daily) for 2 days before, on the day of and 2 days after pemetrexed administration.
All patients eligible for pemetrexed therapy should avoid taking NSAIDs with long elimination half-lives for at least 5 days prior to, on the day of and for 2 days after pemetrexed administration.
Pregnancy and Lactation
Pregnancy
Pemetrexed diarginine is contraindicated during pregnancy.
The manufacturer states that pemetrexed diarginine should not be used during pregnancy, unless clearly necessary. At the time of writing there is limited published information regarding the use of pemetrexed diarginine during pregnancy. Like other antimetabolites, pemetrexed diarginine is suspected to cause serious birth defects when administered during pregnancy. Animal studies have shown reproductive toxicity.
The effect of concurrent therapies must also be considered.
Lactation
Pemetrexed diarginine is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding is discontinued during pemetrexed diarginine therapy. It is not known whether pemetrexed diarginine is excreted in human breast milk, and therefore adverse reactions on the breastfeeding child cannot be excluded.
The effect of concurrent therapies must also be considered.
Side Effects
Abdominal pain
Alanine aminotransferase increased
Alopecia
Anaphylactic shock
Angina
Anorexia
Arrhythmias
Aspartate aminotransferase increased
Bullous pemphigoid
Cardiac failure
Cerebrovascular accident
Chest pain
Colitis
Conjunctivitis
Constipation
Coronary artery disorder
Decrease in creatinine clearance
Decrease in glomerular filtration rate
Dehydration
Dermatitis
Diarrhoea
Dizziness
Dry eyes
Dyspepsia
Eczema
Epidermolysis bullosa
Erythema
Erythema multiforme
Erythematous oedema
Eyelid oedema
Fatigue
Febrile neutropenia
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Haemoglobin decrease
Haemolytic anaemia
Hepatitis
Hyperpigmentation
Hypersensitivity reactions
Increased lacrimation
Infections
Interstitial pneumonitis
Intracranial bleeding
Ischaemic stroke
Keratoconjunctivitis sicca
Leukopenia
Mucosal inflammation
Myocardial infarction
Nausea
Nephrogenic diabetes insipidus
Neutropenia
Oedema
Oesophagitis
Pain
Pancytopenia
Peripheral ischaemia
Peripheral motor neuropathy
Peripheral sensory neuropathy
Pharyngitis
Prurigo
Pruritus
Pulmonary embolism
Pyrexia
Radiation esophagitis
Radiation pneumonitis
Rash
Rectal haemorrhage
Reduced platelet count
Renal failure
Renal tubular necrosis
Sepsis
Serum creatinine increased
Skin exfoliation
Stevens-Johnson syndrome
Stomatitis
Supraventricular arrhythmias
Taste disturbances
Toxic epidermal necrolysis
Urticaria
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: July 2021
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.
Summary of Product Characteristics: Pemetrexed 25mg/ml concentrate for solution for infusion. Aspire Pharma Ltd. Revised June 2021.
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