Methotrexate pre-filled device
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Pre-filled device for injection containing methotrexate.
Drugs List
Therapeutic Indications
Uses
Active juvenile idiopathic arthritis when inadequate response to NSAIDs
Crohn's disease
Psoriasis when other regimens unsuitable/ ineffective
Severe active rheumatoid arthritis
Severe psoriatic arthritis
For the treatment of severe active rheumatoid arthritis in adult patients.
Polyarthritic forms of severe, active juvenile idiopathic arthritis, when the response to NSAIDs has been inadequate.
Treatment of severe recalcitrant disabling psoriasis, which is not adequately responsive to other forms of therapy such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis in adult patients.
Mild to moderate Crohn's disease either alone or in combination with corticosteroid in adult patients refractory or intolerant to thiopurine.
Dosage
Careful monitoring should be carried out after the first dose of methotrexate to exclude idiosyncratic hypersensitivity reactions.
Always consult disease specific protocol for exact dosing and timing instructions.
Folic (non malignant conditions) or folinic acid (malignant conditions) may be required in conjunction with methotrexate use.
In non malignant conditions methotrexate is given once weekly.
Adults
Rheumatoid arthritis
Initial dose: 7.5mg once weekly. The dose may be increased gradually by 2.5mg per week depending on disease activity and patient tolerance.
Note that doses above 20mg/week can be associated with a significant increase in toxicity, particularly bone marrow suppression.
Response to treatment should occur within 4 to 8 weeks. When the therapeutically desired result has been achieved the dose should be gradually reduced to the lowest possible effective maintenance dose.
Psoriasis vulgaris and psoriatic arthritis
Test dose: 5mg to 10mg should be administered one week prior to therapy to detect idiosyncratic adverse reactions.
Initial dose: 7.5mg once weekly. The dose may be increased gradually by 2.5mg per week depending on disease activity and patient tolerance.
Response to treatment should occur within 2 to 6 weeks. When the therapeutically desired result has been achieved the dose should be gradually reduced to the lowest possible effective maintenance dose.
Maximum weekly dose
The maximum recommended weekly dose is 25mg. In some cases a higher weekly dose might be clinically justified, but should not exceed 30mg.
Crohn's disease
Initial dose: 25mg once weekly.
Maintenance dose: 15mg once a week. Response to treatment should occur within 8 to 12 weeks.
Children
Polyarthritic forms of juvenile idiopathic arthritis in children aged 3 to 16 years
10mg to 15mg per metre squared of body surface area (BSA) once weekly.
In therapy refractory cases the weekly dosage may be increased up to 20mg per metre squared of BSA once weekly. An increased monitoring frequency is indicated if the dose is increased.
Children with body surface area less than 0.75 metre squared cannot be treated with these products.
Patients with Renal Impairment
Some manufacturers recommend that the dose should be adjusted as follows:
Creatinine clearance
More than 60ml/minute: No dose reduction required.
30 to 59ml/minute: Use 50% of dose.
Additional Dosage Information
If changing from oral to parenteral administration a reduction of dose may be required due to variable bioavailability of methotrexate after oral administration.
Use in patient with a third distribution space (e.g. pleural effusions and ascites)
As the half life of methotrexate can be prolonged to 4 times the normal length in patients who possess a third distribution space dose reduction or discontinuation of methotrexate administration may be required.
Administration
For subcutaneous injection.
Some brands may also be administered by intramuscular injection.
Contraindications
Children under 3 years
Infection
Serum bilirubin above 85 micromol / L
Alcoholism
Breastfeeding
Buccal ulceration
Gastrointestinal ulcer
Immunodeficiency syndromes
Positive HIV status
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Severe haematological disorder
Severe hepatic impairment
Tuberculosis
Precautions and Warnings
Ascites
Concurrent radiotherapy
Females of childbearing potential
History of herpes zoster infection
History of high alcohol intake
Obesity
Dehydration
Diabetes mellitus
Folate deficiency
Haematological disorder
Hepatic impairment
Hepatitis B
Hepatitis C
History of hepatic impairment
Renal impairment
Significant pleural effusion
Administration of live vaccines is not recommended
Disease reactivation may occur in patients with latent TB
Reduce dose in patients with creatinine clearance of 30-60ml/min
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Ascites should be drained before treatment
Concurrent radiotherapy may increase risk of serious adverse effects
Consider use of folic acid supplement to improve tolerability
For use only by doctors experienced with the action & toxicity of this drug
Give pre-treatment counselling and consideration of sperm cryopreservation
Herpes zoster reactivation possible - consider antiviral prophylaxis
Not all presentations are licensed for all indications
Not licensed for use in children under 3 years
Pleural effusions should be drained before treatment
Advise patient injection is to be administered once a week
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor full blood count and differential WBC before and during therapy
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Perform chest X-ray prior to and periodically during treatment
Urinalysis required pre and post treatment
Elderly: Monitor renal function and consider dose modification
Examine mouth and throat for mucosal changes
Haemopoietic suppression may occur abruptly & with apparently safe dosages
Monitor for drug induced pneumonitis at each visit
Monitor for hepatotoxicity which may occur without other signs of toxicity
Patients with new pulmonary symptoms should be investigated
Take chest X-ray if fever,cough,dyspnoea or other respiratory signs occur
Advise patient to report any symptoms of infections especially sore throats
Advise patient to report breathlessness or cough immediately
Advise patients to report signs of diarrhoea and stomatitis
Reactivation of hepatitis B may occur in chronic carriers
Discontinue if evidence of interstitial lung disease
Discontinue if hepatic enzymes (AST or ALT) become persistently raised
Discontinue if liver function tests become abnormal
Discontinue if malignant lymphomas develop
Discontinue if patient develops respiratory symptoms
Discontinue treatment if profound drop in platelets or WBC occur
If dehydration occurs, discontinue treatment until patient has recovered
Interrupt treatment if diarrhoea or stomatitis occur
Advise patient not to take echinacea products concurrently
Advise patient to consult doctor before any self medication
Advise patients to avoid aspirin and NSAID use
Advise patient to avoid alcohol during treatment
Advise patient excessive dietary caffeine may adversely effect treatment
May cause impaired fertility
Male & female: Contraception required during & for 6 months after treatment
The following tests should be carried out during therapy (at least once a month for the first 6 months and every 3 months after that):
Examination of the mouth and throat for mucosal changes.
Complete blood count with differential blood count and platelets.
Renal function tests.
Liver function tests.
If liver dysfunction occurs, withhold for minimum of two weeks before reintroduction. The need for liver biopsy should be evaluated in patients with the following hepatic risk factors: Excessive prior alcohol consumption, persistent elevation of liver enzymes, anamnestic liver diseases, hereditary liver diseases, diabetes mellitus, obesity, history of significant exposure to hepatotoxic drugs, prolonged methotrexate treatment (cumulative dose of 1.5g or more).
Treatment should be withdrawn from patients with respiratory symptoms and a thorough investigation including chest X-ray should be carried out to exclude infection and/or alveolar haemorrhage. If methotrexate induced lung disease is suspected, methotrexate should not be restarted.
Pregnancy and Lactation
Pregnancy
Methotrexate is contraindicated during pregnancy.
Use of methotrexate during pregnancy is contraindicated by the manufacturer. Extensive studies have shown teratogenic effects including foetal deaths, miscarriages and congenital abnormalities following the use of methotrexate during pregnancy.
Lactation
Methotrexate is contraindicated during breastfeeding.
Use of methotrexate when breastfeeding is contraindicated by the manufacturer. Methotrexate is present in human breast milk at concentrations similar to maternal levels, which appears to carry an increased risk to exposed infants.
Side Effects
Acne
Agranulocytosis
Allergic reaction
Alopecia
Alveolar haemorrhages
Anaemia
Anaphylactic reaction
Anorexia
Anuria
Arthralgia
Asthenia
Asthma
Bladder inflammation
Bone marrow depression
Cirrhosis
Confusion
Conjunctivitis
Convulsions
Cough
Depression
Dizziness
Drowsiness
Dyspnoea
Ecchymosis
Eczema herpeticum
Electrolyte disturbances
Enteritis
Eosinophilia
Erythema
Exanthema
Fatigue
Fever
Furunculosis
Gastro-intestinal ulceration
Gastrointestinal disorder
Gynaecomastia
Haematemesis
Headache
Hepatic disorders (fatty changes)
Hepatic failure
Hepatic fibrosis
Hepatitis
Herpes zoster
Hypogammaglobulinaemia
Hypotension
Impaired fertility
Impotence
Increase in rheumatic nodules
Increase in serum transaminases
Increased susceptibility to infection
Interstitial pneumonitis
Leucopenia
Lipodystrophy (injection site)
Liver atrophy
Local reaction at injection site
Loss of libido
Lymphoma
Meningism
Menstrual disturbances
Metallic taste
Micturition disorders
Mucositis
Myalgia
Oligospermia
Osteonecrosis (primarily of the jaw)
Osteoporosis
Pain
Pancytopenia
Paraesthesia in extremities
Paralysis
Paronychia
Pericardial effusion
Pericardial effusion with associated tamponade
Pericarditis
Pharyngitis
Photosensitivity
Pigmentation of nails
Pleural effusion
Pneumonia
Precipitation of diabetes
Pruritus
Pulmonary fibrosis
Renal failure
Renal impairment
Retinopathy
Sepsis
Skin pigmentation changes
Stevens-Johnson syndrome
Stomatitis
Telangiectasia
Thrombocytopenia
Thromboembolic disorders
Toxic epidermal necrolysis
Toxic megacolon
Urticaria
Vasculitis
Visual disturbances
Vulvovaginal disorders
Wound healing retarded
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: September 2019
Reference Sources
Summary of Product Characteristics: Methofill 7.5mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 10mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 12.5mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 15mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 20mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 22.5mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 25mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 27.5mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 30mg solution for injection in pre-filled injector. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Methofill 50mg/ml solution for injection in pre-filled syringe. Accord Healthcare Limited. Revised September 2018.
Summary of Product Characteristics: Metoject PEN 7.5mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 10mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 12.5mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 15mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 17.5mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 20mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 22.5mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 25mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 27.5mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Metoject PEN 30mg solution for injection in pre-filled pen. Medac-UK. Revised August 2018.
Summary of Product Characteristics: Nordimet solution for injection in pre-filled pen. Nordic Pharma Limited. Revised August 2016.
Summary of Product Characteristics: Zlatal solution for injection in pre-filled syringe. Nordic Pharma. Revised February 2015.
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