Rheumatology regulates the use of cyclophosphamide, these five points to know!

*Recommendations for the use of cyclophosphamide in autoimmune diseases are for medical professionals only

Cyclophosphamide appeared in the clinic in 1958 as a broad-spectrum antitumor drug, and today, it remains one

Combined with the latest review and expert consensus, this paper focuses on the structural mechanism of action of cyclophosphamide in rheumatic diseases, clinical indications, adverse drug reactions, measures and precautions for reducing toxic side effects

First, the structure and mechanism of action

Cyclophosphamide mainly exerts DNA alkylation through phosphoramide nitrogen mustard and a small number of other active metabolites, resulting in crosslinking of DNA and DNA proteins, DNA breakage, thereby reducing DNA synthesis and apoptosis

The effects of cyclophosphamide are not limited to proliferating cells or special types of cells, but different cells have different

2.

For patients with severe organ involvement, with systemic lupus erythematosus, such as lupus nephritis, the most common treatment strategy is intravenous cyclophosphamide to induce remission, followed by maintenance therapy with azathioprine or mycophenolate mofetil to minimize the cytotoxicity

However, long-term use of high-dose cyclophosphamide can lead to a range of serious adverse effects, especially irreversible reproductive toxicity and severe infections

Different guidelines recommend cyclophosphamide dosages for lupus nephritis

Third, the adverse reactions of cyclophosphamide

■ (1) Blood system

Common retrograde bone marrow suppression, manifested by leukopenia and neutropenia, is dose-dependent
.

After a single intravenous use of cyclophosphamide, it takes 8 to 14 days and 21 days for the lymphocyte count to decrease to a minimum and return to the initial level
, respectively.

Long-term use of cyclophosphamide increases the sensitivity of the myelosuppressive effect, so the dose
should be reduced as the duration of administration is prolonged.

■ (2) Urinary system

Cyclophosphamide's bladder toxicity, such as hemorrhagic bladderitis and bladder cancer, is associated with light course of administration, course of treatment, and cumulative dose of cyclophosphamide, a special problem caused by long-term oral cyclophosphamide, which is largely caused
by its metabolite acrolein.

Intravenous cyclophosphamide impact therapy combined with mesna can minimize the toxicity
of cyclophosphamide to the bladder.

■ (3) Reproductive system

Cyclophosphamide can lead to significant gonad toxicity
when used to treat autoimmune diseases.

The risk of developing persistent amenorrhea after treatment with cyclophosphamide was found to be 11% to 59%, and the risk of ovarian failure depended more on the patient's age and cumulative dose of cyclophosphamide than on
the route of administration.

■ (4) Infection

Infection is a common complication, including a variety of common infections and opportunistic infections
.

The degree of cyclophosphamide immunosuppression is related to different regimens of combined glucocorticoid therapy
.

For example, Pneumonis carinii pneumonia is a severe but preventable opportunistic infection that can occur during the treatment of
systemic vasculitis with cyclophosphamide and methotrexate.

■ (5) Malignant tumors

The carcinogenic effect of cyclophosphamide may be related to cumulative doses, and when the cumulative dose exceeds 100 g, the risk of malignant tumors is higher
.

Although current data do not quantify the long-term risk of cyclophosphamide intravenous shock regimens, the risks may be much lower than those of oral cyclophosphamide regimens
.

■ (6) Lungs

The incidence of cyclophosphamide causing pulmonary toxicity is less than 1%.


Early pneumonia occurs after 1 to 6 months of cyclophosphamide use, which can be relieved with discontinuation of the drug or with corticosteroids
.

■ (7) Other toxic side effects

Varying degrees of reversible alopecia
may occur both daily orally and each monthly intravenous injection of cyclophosphamide.

Cardiotoxicity (often present in tumor treatment and dose-related) and water poisoning (caused by excessive secretion of antidiuretic hormone) are rare
at standard doses.

Fourth, measures to reduce toxicity

Measures to reduce toxicity include adjusting the dose of the drug to avoid severe leukopenia (WBC count < 3000/mm under the daily oral regimen and < 2000/mm is granulocytopenia)
under the intravenous regimen).

In order to reduce the risk of infection in patients who also use high doses of glucocorticoids, glucocorticoids should be reduced in time after clinical effects are obtained, and glucocorticoids can be taken
every other day during the maintenance therapy phase.

Oral cyclophosphamide should be taken in the morning and drink plenty of water to empty the bladder to reduce the time
that acrolein stays in the urine and bladder.

Drugs
to prevent Pneumabria carinii pneumonia are often used when cyclophosphamide and glucocorticoids are used in high doses, especially during the phase of induction of remission.

Patients treated with cyclophosphamide, especially those with hemorrhagic cystitis, have an increased risk of bladder cancer, so regular urinalysis and urine cytology are required throughout their lives, and if abnormalities are found, further cystoscopy is required
.

Fifth, the medication precautions of cyclophosphamide

(1) Monitoring blood and urine routine: once a week in the first month, once every two weeks in the second to third months, and once a
month after that.

(2) Cyclophosphamide
is contraindicated in pregnant women and lactating patients.

(3) When applying cyclophosphamide, vaccination
should be avoided as much as possible.

(4) Avoid combining with azathioprine, cyclosporine, antifungals, antibiotics, and anticoagulants
.

(5) Actively prevent infection: daily attention should be paid to keeping warm, preventing colds, and if there is fever, it should be timely to seek medical treatment to strengthen nutrition to improve the body's resistance
.
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Source of this article: Medical Rheumatism immunology channel This article author: Jenny This article review: Chen Xinpeng Deputy Chief Physician This article responsible editor: Orange Copyright

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