There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=* Condition1
<!--Warnings-->
|warnings=* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=* Oral
* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose====Acute Overdose===
====Signs and Symptoms====
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
<!--Pharmacology-->
<!--Drug box 2-->
|drugBox=<!--Mechanism of Action-->
|mechAction=*
<!--Structure-->
|structure=*
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
==Overview==
<!--Pharmacodynamics-->
'''Cyclophosphamide''' (the generic name for Cytoxan, Neosar), also known as cytophosphane, is a [[nitrogen mustard]] [[alkylating antineoplastic agent|alkylating agent]], used to treat various types of [[cancer]] and some [[autoimmune disorder]]s. It is a "[[prodrug]]"; it is converted in the [[liver]] to active forms that have [[chemotherapy|chemotherapeutic]] activity.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
==Uses==
<!--Pharmacokinetics-->
The main use of cyclophosphamide is together with other chemotherapy agents in the treatment of [[lymphoma]]s, some forms of [[leukemia]] and some solid tumors. It is a chemotherapy drug that works by slowing or stopping cell growth. It also works by decreasing the immune system's response to various diseases.
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
In addition, its use is becoming more common in [[autoimmune disease]]s where [[disease-modifying antirheumatic drug]]s (DMARDs) have been ineffective. [[Systemic lupus erythematosus]] (SLE) with severe [[lupus nephritis]], for example, may respond to pulsed cyclophosphamide. However in 2005, standard treatment for lupus nephritis changed to [[Mycophenolic acid|MMF]] from cyclophosphamide.
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
It is also used to treat [[Minimal Change Disease]] and rheumatoid arthritis. It is still used for [[Wegener's granulomatosis]].
<!--Clinical Studies-->
The trade name is Endoxan.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
==Pharmacokinetics/Pharmacodynamics==
<!--How Supplied-->
Cyclophosphamide is converted by mixed function [[oxidase]] [[enzyme]]s in the liver to active metabolites. The main active metabolite is 4-hydroxycyclophosphamide. 4-hydroxycyclophosphamide exists in [[chemical equilibrium|equilibrium]] with its [[tautomer]], aldophosphamide. Most of the aldophosphamide is oxidised by the enzyme [[aldehyde dehydrogenase]] (ALDH) to make carboxyphosphamide. A small proportion of aldophosphamide is converted into phosphoramide mustard and [[acrolein]]. Acrolein is toxic to the [[urinary bladder|bladder]] [[epithelium]] and can lead to [[hemorrhagic cystitis]]. This can be prevented through the use of aggressive hydration and/or [[Mesna]].
|howSupplied=*
Recent clinical studies have shown that cyclophosphamide induce beneficial [[Immunomodulator|immunomodulatory]] effects in the context of adoptive immunotherapy. Although the mechanisms underlying these effects are not fully understood, several mechanisms have been suggested based on potential modulation of the host environment, including:
# Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts
# Induction of T cell growth factors such as type I IFNs, and/or
# Enhanced grafting of adoptively transferred tumor-reactive effector T cells by the creation of an immunologic space niche.
Thus, cyclophosphamide pre-conditioning of recipient hosts (for donor T cells) has been used to enhance immunity in naïve hosts, and to enhance adoptive T cell immunotherapy regimens as well as active vaccination strategies, inducing objective anti-tumor immunity.
<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
==Mode of action==
<!--Precautions with Alcohol-->
The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells which have low levels of ALDH.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Phosphoramide mustard forms DNA crosslinks between (interstrand crosslinkages) and within (intrastrand crosslinkages) DNA strands at guanine N-7 positions. This leads to cell death.
<!--Brand Names-->
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
Cyclophosphamide has relatively little typical chemotherapy toxicity as ALDHs are present in relatively large concentrations in [[Hematopoietic stem cell|bone marrow stem cells]], [[liver]] and [[intestine|intestinal]] [[epithelium]]. ALDHs protect these actively proliferating tissues against toxic effects phosphoramide mustard and acrolein by converting aldophosphamide to carboxyphosphamide that does not give rise to the toxic metabolites (phosphoramide mustard and acrolein).
<!--Look-Alike Drug Names-->
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
==Side-effects==
<!--Drug Shortage Status-->
Many people taking cyclophosphamide do not have serious side effects. [[Adverse drug reaction|Side-effects]] include [[chemotherapy-induced nausea and vomiting]] (CINV), [[bone marrow suppression]], stomach ache, diarrhea, darkening of the skin/nails, [[alopecia]] (hair loss) and [[lethargy]]. [[Hemorrhagic cystitis]] is a frequent complication, but this is prevented by adequate fluid intake and [[Mesna]] (sodium 2-mercaptoethane sulfonate). Mesna is a sulfhydryl donor and binds [[acrolein]].
|drugShortage=
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|fileName={{PAGENAME}}11.png
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{{LabelImage
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<!--Pill Image-->
Cyclophosphamide is itself [[carcinogen]]ic, potentially causing transitional cell [[carcinoma]] of the bladder as a long-term complication. It can lower the body's ability to fight an infection. It can cause temporary or (rarely) permanent sterility. Although it is used to treat cancer, it may increase the risk of developing another form of cancer, sometimes months to years after treatment.
Other (serious) side effects include:
* pink/bloody urine,
* unusual decrease in the amount of urine,
* mouth sores,
* unusual tiredness or weakness,
* joint pain,
* easy bruising/bleeding,
* stopping of menstrual periods,
* existing wounds that are slow healing.
==History==
<!--Label Display Image-->
Cyclophosphamide and the related [[nitrogen mustard]]-derived alkylating agent [[ifosfamide]] were developed by Norbert Brock and ASTA (now Baxter Oncology). Brock and his team synthesised and screened more than 1,000 candidate oxazaphosphorine compounds.<ref>{{cite journal |author=Brock N |title=The history of the oxazaphosphorine cytostatics |journal=Cancer |volume=78 |issue=3 |pages=542-7 |year=1996 |pmid=8697402 }}</ref> They converted the base nitrogen mustard into a non-toxic "transport form". This transport form was a pro-drug, subsequently [[active transport|actively transported]] into the cancer cells. Once in the cells, the pro-drug was [[enzyme|enzymatically]] converted into the active, toxic form.
The first clinical trials were published at the end of the 1950s.<ref>{{cite journal|author=Wilmanns, H.|journal= Asta-Forschung und Therapie|year= 1958}}</ref><ref>{{ cite journal|author=Gross, R., and Wulf, G. |title=Klinische und experimentelle Erfahrungen mit zyk
lischen und nichtzyklischen Phosphamidestern des N-Losl in der Chemotherapie von Tumoren|journal=Strahlentherapie|volume= 41 (Sonderband III)|pages= 361-367|year= 1959}}</ref><ref>{{cite journal |author=Brock N |title=Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture |journal=Cancer Res. |volume=49 |issue=1 |pages=1-7 |year=1989 |pmid=2491747 |doi=}}</ref>
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Black Box Warning
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Overview
Cyclophosphamide is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
Dosing Information
Dosage
Condition2
Dosing Information
Dosage
Condition3
Dosing Information
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Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Cyclophosphamide in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cyclophosphamide in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Cyclophosphamide in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Cyclophosphamide in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cyclophosphamide in pediatric patients.
Contraindications
Condition1
Warnings
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Cyclophosphamide in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Cyclophosphamide in the drug label.
