There are many types of immunosuppressants for the treatment of SLE, such as alkylating agents, azathioprine, cyclosporine, methotrexate and mycophenolate mofetil, among which cyclophosphamide 188 amide (cyclophosphamide ) is a type of alkylating agent. There are many patients who take or intravenously inject cyclophosphamide, so do everyone know enough about cyclophosphamide? Does anyone know how to prevent shingles caused by it?
1. Cyclophosphamide identity authentication:
Cyclophosphamide itself is an inactive drug that can exert therapeutic effects and produce toxic side effects in SLE.
Cyclophosphamide is a cell cycle non-specific cytotoxic drug that can directly act on DNA to cause cell death. Its recognized immunosuppressive mechanisms include changing macrophage function; increasing prostaglandin E2 production; changing gene transcription and affecting lymphocyte function.
Both oral and intravenous administration can reduce B cells, but do not affect IgG, IgA, and IgM levels.
Intravenous administration can reduce the levels of CD4+ and CD8+ T cells, but the level of CD4+ T cells continues to be low after drug withdrawal, thereby achieving the effect of immune regulation through the adjustment of Th cell/Ts cell levels. This is the intravenous circuit Pharmacological basis for phosphoramide pulse therapy.
2. What are the effects of using cyclophosphamide in patients with impaired liver function?
The absorption effect of cyclophosphamide is the same when administered orally and intravenously. About 20% is excreted by the kidneys and 80% is metabolized by the liver. When the creatinine clearance is lower than 30 ml/min, drug toxicity increases, and the dose needs to be adjusted; and cyclophosphamide cannot be completely removed by dialysis, and the dose of dialysis patients also needs to be lowered. There is not much research data on whether the dosage of cyclophosphamide needs to be adjusted in patients with hepatic insufficiency, but it is generally believed that the liver is the place where cyclophosphamide is metabolized into active products. Impaired liver function will also affect the drug effect, so it is generally not necessary. Adjust dosage.
3. What are the toxic and side effects of cyclophosphamide?
(1) Tumor It is widely recognized that cyclophosphamide can cause tumors. It is safer to take the total oral dose less than 10g, while more than 100g will almost certainly cause tumors.
(2) Hemorrhagic cystitis is mainly caused by acrolein, a metabolite of cyclophosphamide, and about 50% of patients can progress to transitional cell carcinoma of the urinary tract. Intravenous cyclophosphamide administration with adequate hydration can reduce the toxicity of acrolein and make hemorrhagic cystitis almost non-existent.
(3) Myelosuppression: For other alkylating agents, such as nitrogen mustard, cyclophosphamide has less impact on bone marrow. After intravenous administration, the decrease of lymphocytes appears on the 7th to 10th day, and the decrease of neutrophils Reduction occurs on days 10 to 14, and recovery occurs on days 21 to 28.
(5) Cyclophosphamide rarely causes thrombocytopenia, but long-term use may cause thrombocytopenia.
(6) Reproductive system Due to its killing effect on dividing cells, it is most damaging to mature follicles with reproductive function, causing the levels of estrogen and progesterone to decrease, the levels of follicle-stimulating hormone to increase, and more mature follicles to be released. The mature follicles that are most sensitive to cyclophosphamide decrease faster, eventually leading to amenorrhea.
Current reports suggest that the older you are, the greater the risk, especially for female patients over 30 years old; the greater the dose, the greater the toxicity; oral toxicity is greater than intravenous administration. Cyclophosphamide has also been reported to cause fetal malformations and is not suitable for use by pregnant women. Cyclophosphamide can cause azoospermia in men, which is generally irreversible. Unlike women, men rarely have abnormalities in reproductive hormone levels.
(7) Infection Cyclophosphamide is often used in combination with glucocorticoids to treat SLE patients, which increases the chance of infection, especially herpes zoster infection.
4. With so many side effects, why do we still use it?
Cyclophosphamide is still the most approved drug for the treatment of lupus nephritis. Oral administration of 2 mg/(kg . d) has a tendency to be replaced by intravenous pulse therapy due to greater side effects. Intravenous treatment methods include once a week, once every 2 weeks, once a month, etc. Various reports vary, but most of them lack long-term follow-up or have no control group.
5. Is there any authoritative test to prove the efficacy of cyclophosphamide?
Organobentonite rheology additive
In 1992, Boumpus and other treatment plans were extended for 2 years after a 6-month course of treatment, with a dose of 0.5~1.0g/m2, once every 3 months, which is different from the treatment of lupus with hormones alone. There was no significant difference in nephritis program comparison within 5 years, but there was a statistically significant difference in the protection of renal function over 5 years, mainly because renal fibrosis will not be further aggravated by hormone application. The mortality rate of the cyclophosphamide group was significantly lower than that of the steroid group, and patients with prolonged use of cyclophosphamide were better than the steroid group and the non-prolonged group in terms of recurrence and renal function deterioration, with statistical significance.
PS: Existing data indicate that cyclophosphamide is suitable for patients who are resistant to hormones, and there is no evidence that intravenous administration is better than oral treatment.
6. Is there any research progress on cyclophosphamide in recent years?
The American Journal of Rheumatology published an article in July this year, “Herpes Zoster After Systemic Lupus Erythematosus or Vasculitis Treated with Cyclophosphamide”
It is a study done by Professor Camille Garnier and others
This study aimed to evaluate the incidence and risk factors of herpes zoster with intravenous cyclophosphamide (CYC) and valacyclovir (VCV) prophylaxis in patients with systemic vasculitis or systemic lupus erythematosus (SLE). The protective effect of medication.
This retrospective study included all adults with SLE or SLE treated with intravenous cyclophosphamide at the University Hospital of Toulouse, France, between 2011 and 2015.Patients with chronic vasculitis. Herpes zoster incidence was documented using medical records, laboratory data, and patient interviews. Univariate Cox models were calculated to evaluate risk factors for herpes zoster and the protective effect of VCV prophylaxis.
The results showed that among the 19 patients who used valacyclovir, none developed herpes zoster during the follow-up period.
The incidence of herpes zoster is high in patients with systemic vasculitis and SLE who receive intravenous cyclophosphamide. Intravenous cyclophosphamide may cause postherpetic neuralgia. Prophylactic valacyclovir should be considered, especially if lymphopenia is <500/μl at the start of treatment and within one year thereafter.
