Cyclophosphamide cyc is an alkylating agent that was introduced into clinical practice as a chemotherapeutic agent but has also been used to treat a number of systemic autoimmune diseases. Cyclophosphamide can sometimes cause a decrease in your blood count, liver problems, hair loss and mouth ulcers. The unchanged drug has an elimination halflife of 3 to 12 hours. Cyclophosphamide 500 mg powder for solution for injection or. These findings establish that cyclophosphamide treatment can modulate hepatic p450 activities through multiple mechanisms and in a manner that may alter p450 metabolism of cyclophosphamide and perhaps other anticancer drugs. Cyclophosphamide is a drug that is used primarily for treating several types of cancer. Effects of cyclophosphamide on b and tlymphocytes in rheumatoid arthritis.
These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells. At higher doses, it interrupts cell cycle by forming dna cross linking, dna lesions. Cyclophosphamide is used to treat various types of cancer. Therapeutic use of cyclophosphamide and its cytotoxic action. All of the available evidence indicates that cyclophosphamide exerts its carcinogenic activity via a genotoxic mechanism. A challenge for researchers article pdf available in journal of pharmacy research 48. Its cytotoxic effect is mainly due to crosslinking of strands of dna and rna, and to inhibition of protein synthesis. Results of this study suggest that cyclophosphamide does not impair development of a population of specifically sensitized ttype lymphocytes. In each individual case the potential benefit of the treatment should be weighed against the potential risk for the foetus. Mechanism of action and pharmacokinetics indications and status adverse effects dosing administration guidelines special precautions interactions recommended clinical monitoring supplementary public funding references disclaimer. It is best to read this information with our general information about chemotherapy and the type of cancer you have your doctor will talk to you about this treatment and its possible side effects before you agree consent to have treatment.
Exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn. However, several components of the expression phase are affected. Carcinogenesis, mutagenesis, impairment of fertility. Cyclophosphamide 500 mg powder for solution for injection. Although women taking cyclophosphamide can stop having periods, they can still become pregnant, so an effective form of birth control to prevent pregnancy should be used while taking this medication. It is considered to be cell cycle phasenonspecific. Reviewing the chemistry and pharmacology of cyclophosphamide is crucial for understanding its wide therapeutic applicability.
Cyclophosphamide is an alkylating agent of the nitrogen mustard type. Mechanism of action and toxicity of cyclophosphamide the immunosuppressive actions of cyclophosphamide are complex. Cyclophosphamide is an alkylating drug indicated for treatment of. Development of sterility appears to depend on the dose of cyclophosphamide, duration of therapy, and the state of gonadal function at the time of treatment.
Cyclophosphamide is commonly used with doxorubicin hydroxydaunorubicin, vincristine oncovin, and prednisone known as the chop regimen, with or without other agents, in the treatment of various types of intermediategrade nonhodgkin lymphoma. Cyclophosphamide cp, also known as cytophosphane among other names, is a medication. This means that the alkylating action of this drug is specifically directed. It is transformed via hepatic and intracellular enzymes to active alkylating metabolites. Cyclophosphamide in its parent form does not have direct cytotoxic effects. This metabolite is only formed in cells that have low levels of aldh. Oral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing. Over the past 20 years, increased understanding of the mechanism of action of 5fu has led to the development of strategies that. Cytoxan cyclophosphamide for injection, usp cytoxan tablets. Cyclophosphamide is an alkylating agent, and prevents cell division primarily by crosslinking dna and rna strands. Cyclophosphamide is used commonly for the treatment of chronic lymphocytic lymphoblastic leukaemia. Cyclophosphamide mechanism, indication, contraindications. This treatment resulted in generalized depletion of lymphoid cells, including lymphopenia, and a substantial reduction in the number of macrophages found in induced.
Mechanism of action and pharmacokinetics indications and status adverse effects dosing administration guidelines special precautions. Vb6bearing t cells directed to minor lymphocyte stimu. Therapeutic use of cyclophosphamide and its cytotoxic. In the liver, cyclophosphamide is converted to active metabolites including phosphoramide mustard, which binds to and crosslinks dna and rna, thereby inhibiting dna. The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. Ndechloroethylation to therapeutically inactive but neurotoxic metabolites occurs primarily via cyp3a4. Pdf therapeutic use of cyclophosphamide and its cytotoxic action. A course of cyclophosphamide administered to guinea pigs after immunization with mycobacteria led to a transient inhibition of cutaneous hypersensitivity to tuberculin protein. Tecemotide is a muc1 antigenspecific therapeutic cancer vaccine. Fidanze, in comprehensive medicinal chemistry ii, 2007. Cyclophosphamide mechanism of action in preclinical. It is one of the most potent immunosuppressive drugs available. It is a chemotherapy drug that works by slowing or stopping cell growth cyclophosphamide also works by decreasing your immune. Cyclophosphamide mechanism of action in preclinical tecemotide studies ken hance1, robert tighe1, jin qi1, william hastings1, guozhong qin1, bo marelli1, hong wang1, huakui yu1, yanping zhang1, xiaomei xu1, wilson guzman1, masie wong1, giorgio kradjian1, beatrice brunkhorst1, helen sabzevari1, yan lan1, robert hofmeister1, michael wolf2 from.
Cyclophosphamide fda prescribing information, side. Following activation of cyclophosphamide in the liver, multiple metabolites appear in the circulation with varying degrees of immunosuppressive action and toxicity. Pdf cyclophosphamide mechanism of action in preclinical tecemotide studies find, read and cite all the research you need on researchgate. This medicine may cause harm to the unborn baby or loss of the unborn baby if you take it while you are pregnant. Rituximab versus cyclophosphamide for ancaassociated. Taking cyclophosphamide during pregnancy is very dangerous to an unborn child. Download fulltext pdf download fulltext pdf cyclophosphamide mechanism of action in preclinical tecemotide studies article pdf available november 20 with 601 reads. Cyclophosphamide cyc is an alkylating agent that was introduced into clinical practice as a chemotherapeutic agent but has also been used to treat a number of. Cyclophosphamide anhydrous is the anhydrous form of cyclophosphamide, a synthetic nitrogen mustard alkylating agent, with antineoplastic and immunosuppressive activities. Cyclophosphamide is the generic name of the prescription drug cytoxan, a chemotherapy drug for people with certain cancers. The clinical significance of this interaction is unknown. Cyclophosphamide tablets, usp are for oral use and contain 25 mg or 50 mg cyclophosphamide anhydrous.
Cyclophosphamide is used alone or in combination with other medications to treat hodgkins lymphoma hodgkins disease and nonhodgkins lymphoma types of cancer that begin in a type of white blood cells that normally fights infection. Cyclophosphamide for injection, usp is a sterile white powder containing. It is eliminated primarily in the form of metabolites. The activation mechanism is believed to require an initial oxidative. Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4hydroxyl metabolites, and shortened t12 values following repeated administration. Cyclophosphamide can also cause infertility in both men and women.
Inactive ingredients in cyclophosphamide tablets are. Cyclophosphamide is bio transformed principally in the liver to active alkylating metabolites by microsomal oxidase system. Cyclophosphamide injectable solution is a prescription medication used to treat many types of cancer. Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies.
Its prescribed for nonhodgkin lymphoma, hodgkin lymphoma, multiple. Molecular mechanism involved in cyclophosphamideinduced. Jun 21, 2019 cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. The difference in pharmacological effect depends on the metabolism of the drug, the dose administered, dosing schedule and timing of the dosing. Nov 01, 2019 women treated with cyclophosphamide injection may go through menopause at a younger age than normal. Cyclophosphamide was considered by previous iarc working groups in. Mechanisms of action cyclophosphamide, a nitrogen mustard, is an alkylating agent from the oxazophosphorine group figure 1. Jun 26, 2017 considering the data from human case reports, animal studies and the mechanism of action of cyclophosphamide, its use during pregnancy, in particular during the first trimester, is not recommended.
Apr 07, 2014 cyclophosphamide mechanism of action the main effect of cyclophosphamide is due to its metabolite phosphoramide mustard phosphoramide mustard forms dna crosslinks between interstrand crosslinkages and within intrastrand crosslinkages dna strands at guanine n7 position, this eventually leads to cell death 4. The mechanism of action is thought to involve crosslinking of tumor cell dna. Effects of cyclophosphamide on b and tlymphocytes in. As a single agent for induction therapy, cyclophosphamide is typically given as a dose of 100 mg m. Phosphoramide mustard forms dna crosslinks both between and within dna strands at guanine n7 positions known as interstrand and intrastrand crosslinkages, respectively. A healthcare provider will give you this medication. Caution should be exercised when handling and preparing cyclophosphamide for injection, usp lyophilized powder, or bottles containing cyclophosphamide tablets. It is a prodrug that is converted to its active metabolites in liver. Mar 06, 2020 the mechanism of action of cyclophosphamide in autoimmune diseases is thought to involve immunosuppression due to destruction of immune cells via dna crosslinking. Cyclophosphamide side effects, warnings, dosage, and more.
In phase iii clinical studies, delivery of tecemotide is preceded by a single low dose of cyclophosphamide cpa to inhibit regulatory t cells tregs and enhance the response to the tumorassociated antigen. Cyclophosphamide induced sterility may be irreversible in some patients. Clinical pharmacology of cyclophosphamide cancer research. Cyclophosphamide has also been used as a single agent in the treatment of lowgrade lymphomas. Cyclophosphamide for injection, usp is a sterile white powder containing cyclophosphamide monohydrate. Aldophosphamide undergoes nonenzymatic breakdown into both acrolein and phosphoramide mustard which are also. Cyclophosphamide is an alkylating cytotoxic drug that is toxic not only to. Acrolein and phosphoramide are the active compounds, and they slow the growth of cancer cells by interfering with the actions of deoxyribonucleic acid dna within the cancerous cells. Women must use birth control while taking cyclophosphamide injection and for some time after the last dose. Cyclophosphamide is well absorbed after oral administration with a bioavailability greater than 75%.
Mechanisms of cyclophosphamide action on hepatic p450 expression1. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Several studies have examined the mechanism of action of cyclophosphamide. Mechanisms of cyclophosphamide action on hepatic p450. Cyclophosphamide exhibit the bimodal mechanism of antitumor action with cardiotoxic effect and immunomodulatory effects. It was also reported to act as a mutagen and dnadamaging agent in bacteria. Cyclophosphamide fda prescribing information, side effects. Cyclophosphamide is used to treat breast cancer, lung cancer, leukaemia, lymphoma, and myeloma. Cyclophosphamide is used in combination with busulfan as a conditioning regimen before allogeneic haematopoietic progenitor cell transplantation in patients with chronic myelogenous leukaemia. Dailymed cyclophosphamide injection, powder, for solution. An activated form of cyclophosphamide, phosphoramide mustard, alkylates, or binds, to dna.
Mechanism of action of posttransplantation cyclophosphamide. In order to work, cyclophosphamide first is converted by the liver into two chemicals, acrolein and phosphoramide. Theres also a slightly increased risk of certain types of cancer, particularly bladder cancer, but cyclophosphamide will not be recommended for you unless the benefits of treatment are thought to be much greater than the risks. Cytoxan cyclophosphamide for injection, usp cytoxan.
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