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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Children
Patients with Renal Impairment
Patients with Hepatic Impairment
Additional Dosage Information

100mg to 300mg daily, as a single or divided dose.

Some brands suggest doses of 50 to 250mg/square metre daily, with doses towards the upper end of the range used only for short courses.

Doses may be amended based on local treatment protocol or at the discretion of the physician.

A reduction in dosage is recommended when used with other chemotherapeutic drugs or radiation therapy.

Severe Systemic Rheumatoid Arthritis (unlicensed)

1mg/kg to 1.5mg/kg per day.

Precautions and Warnings

Cyclophosphamide should only be prescribed and administered under the supervision of a specialist.

Whilst the doses stated are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Caution should be exercised in patients who are elderly, debilitated, or evidence of myelosuppression.

Care should be taken when treating patients who have recently received or are receiving concurrent treatment with radiotherapy or cytotoxic agents.

Cardiotoxicity may be induced in patients who have had, or are receiving mediastinal irradiation, doxorubicin or pentostatin. This has also been reported with high doses of cyclophosphamide, and in such instances, therapy should be stopped and appropriate treatment initiated.

Perform regular blood counts. Withhold therapy if severe bone marrow depression occurs and reduce dose in lesser degrees of bone marrow depression.

If the leucocyte count is below 4 x 10 to the power of 9 per litre and/or the platelet count is below 100 x 10 to the power of 9 per litre, treatment with cyclophosphamide should be temporarily withheld until the blood count returns to normal.

Cyclophosphamide is not recommended in patients with plasma creatinine greater than 120 micromole per litre (1.5mg/100ml), bilirubin greater than 17 micromole per litre (1mg/100ml) or with transaminases or alkaline phosphatase more than 2-3 times the normal value. In all such cases, dosage should be reduced.

Treatment may lead to inappropriate secretion of anti-diuretic hormone leading to fluid retention, hyponatraemia and water intoxication. In this case, institute diuretic treatment.

Urine should be sent for laboratory analysis before and at the end of each course of treatment.
The patient should be monitored for evidence of haematuria at regular intervals throughout the treatment period, and instructed to report any signs or symptoms of cystitis.
Cyclophosphamide should be avoided in patients with cystitis from any cause until it has been treated.

Ensure adequate hydration and maintain fluid balance. Avoid alkalinisation of urine.

Urotoxic effects may be reduced with concurrent administration of mesna. If mesna is used to reduce urothelial toxicity, frequent emptying of the bladder should be avoided.

Cyclophosphamide may have an adverse effect on the gonads. Patients should be advised that amenorrhoea and azoospermia may occur which may be irreversible. Therefore counselling regarding sperm conservation in males should be given prior to treatment and female patients should receive counselling regarding subsequent pregnancies as reproductive life may be shortened by the onset of premature menopause. Cyclophosphamide may induce permanent sterility in children.

Contraception is advised for both sexes during and for 3 months after treatment.

Anti-emetics may be given before and during therapy to reduce nausea and vomiting.

As with other antineoplastic agents, there is a risk of secondary neoplasms as long-term sequelae of treatment. An increased risk of bladder cancer and acute leukaemia has been associated with cyclophosphamide.

Close monitoring of blood glucose levels in diabetic patients is recommended. Cyclophosphamide can potentiate the hypoglycaemic effects of certain antidiabetic agents and alter carbohydrate metabolism. Both hypoglycaemia and hyperglycaemia have been observed.

Contains lactose use with caution in patients with glucose-galactose malabsorption or lactose intolerance.

Use in Porphyria

In patients with porphyria, cyclophosphamide may be used with caution if no safer alternative is available.

The Drug Database for Acute Porphyria consider cyclophosphamide to be probably not porphyrogenic when used in low does.

Pregnancy and Lactation

Pregnancy

Cyclophosphamide should not be used during pregnancy, especially in the first trimester, unless the expected benefit is thought to outweigh the substantial risk to the foetus.
Cyclophosphamide has been shown to be teratogenic, mutagenic and has carcinogenic potential.

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 at https://www.toxbase.org/ .

Licensed in pregnancy? - No, contraindicated

Known human teratogen? - Yes

Animal data - Malformations of the central nervous system, craniofacial area and the skeleton have been observed.

Crosses placenta? - Yes

Effects on the foetus - Small case series exist for first trimester exposure describing craniofacial abnormalities, limb defects, growth retardation, eye and ear malformations. Pancytopenia, reduced birth weight and an increase in the incidence of premature births have been documented following second and/or third trimester exposure to cyclophosphamide.

Lactation

Nursing mothers should not breastfeed during treatment or for 36 to 48 hours after final dose. Cyclophosphamide is excreted into human breast milk in large quantities and breast fed infants may experience bone marrow suppression.

Individual case reports have demonstrated adverse effects such as neutropenia occurring in the neonate up to 9 days after final dose and cessation of feeding.

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

Presentation

Tablets containing 50mg cyclophosphamide

Drugs List

cyclophosphamide 50mg tablets

Therapeutic Indications

Uses

Treatment of malignant disease either as a single agent or in combination with other cytotoxic drugs, radiotherapy or surgery.

Unlicensed Uses

Severe systemic rheumatoid arthritis
Steroid sensitive nephrotic syndrome

Dosage

Cyclophosphamide should only be prescribed and administered under the supervision of a specialist.

Dosage and frequency of administration should be determined by the tumour type, tumour stage, general condition of the patient and whether other chemotherapy or radiotherapy is to be administered concurrently.

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

100mg to 300mg daily, as a single or divided dose.

Some brands suggest doses of 50 to 250mg/square metre daily, with doses towards the upper end of the range used only for short courses.

Doses may be amended based on local treatment protocol or at the discretion of the physician.

A reduction in dosage is recommended when used with other chemotherapeutic drugs or radiation therapy.

Severe Systemic Rheumatoid Arthritis (unlicensed)
1mg/kg to 1.5mg/kg per day.

Children

See Adult Dosage but doses may be amended based on local treatment protocol or at the discretion of the physician. Children have received cyclophosphamide with no specific problems reported.

Steroid sensitive nephrotic syndrome (unlicensed):
Children aged 3 months to 18 years
2mg/kg to 3 mg/kg per day for 8 weeks.

Patients with Renal Impairment

Cyclophosphamide is not recommended in patients with plasma creatinine greater than 120 micromole per litre (1.5mg/100ml).
Manufacturers suggest dose adjustment may be required but give no specific impairment guidance.

The Renal Drug Handbook suggests the following dose adjustments:
GFR 20ml/minute to 50ml/minute: no dose adjustment
GFR 10ml/minute to 20ml/minute: 75% to 100% of normal dose
GFR less than 10ml/minute: 50% to 100% of normal dose

Patients with Hepatic Impairment

Cyclophosphamide is not recommended in patients with bilirubin greater than 17 micromole per litre (1mg/100ml) or with transaminases or alkaline phosphatase more than 2-3 times the normal value.
Manufacturers suggest dose adjustment may be required but give no specific impairment guidance.

Additional Dosage Information

Treatment should be continued until a clear remission or improvement is seen or be interrupted when the extent of leucopenia becomes unacceptable.

A minimum urine output of 100ml per hour should be maintained during therapy with conventional doses to avoid cystitis. If larger doses are used, an output of at least this level should be maintained for 24 hours following administration, if necessary by forced diuresis.

Administration

For oral administration.

Cyclophosphamide tablets should be swallowed with plenty of fluid, without chewing. This should be done preferably on an empty stomach but if gastric irritation is severe, the tablets may be taken with meals. The tablets are coated and should not be divided before use.

Cyclophosphamide should be given early in the day and the bladder voided frequently. The patient should be well hydrated and maintained in fluid balance. Mesna may be given concurrently to reduce the urotoxic effects of cyclophosphamide and in this case, frequent bladder emptying should be avoided.

Handling

Standard guidelines on handling cytotoxic drugs should be followed:
1. Trained personnel should reconstitute cytotoxics;
2. Reconstitution should be carried out in designated areas;
3. Protective clothing (including gloves) should be worn;
4. The eyes should be protected and means of first aid should be specified;
5. Pregnant staff should not handle cytotoxics;
6. Adequate care should be taken for the disposal of waste material, including syringes, containers and absorbent material.

Contraindications

Acute infections
Bone marrow aplasia
Urinary tract infection
Non-malignant disease (except as an immunosuppressant in life-threatening cases)
Haemorrhagic cystitis
Pregnancy (see Pregnancy section)
Breastfeeding (see Lactation section)
Galactosaemia