Editing Chloramphenicol (section)

==Adverse effects==

===Aplastic anemia===

The most serious [[adverse drug reaction|side effect]] of chloramphenicol treatment is [[aplastic anaemia|aplastic anaemia ('AA')]]. This effect is rare but sometimes fatal. The risk of AA is high enough that alternatives should be strongly considered. Treatments are available but expensive. No way exists to predict who may or may not suffer this side effect. The effect usually occurs weeks or months after treatment has been stopped, and a genetic predisposition may be involved. It is not known whether monitoring the [[blood count]]s of patients can prevent the development of aplastic anaemia, but patients are recommended to have a baseline blood count with a repeat blood count every few days while on treatment.<ref>{{cite journal | vauthors = Hammett-Stabler CA, Johns T | title = Laboratory guidelines for monitoring of antimicrobial drugs. National Academy of Clinical Biochemistry | journal = Clinical Chemistry | volume = 44 | issue = 5 | pages = 1129–1140 | date = May 1998 | pmid = 9590397 | doi = 10.1093/clinchem/44.5.1129 | doi-access = free }}</ref> Chloramphenicol should be discontinued if the complete blood count drops. The highest risk is with oral chloramphenicol (affecting 1 in 24,000–40,000)<ref>{{cite journal | vauthors = Wallerstein RO, Condit PK, Kasper CK, Brown JW, Morrison FR | title = Statewide study of chloramphenicol therapy and fatal aplastic anemia | journal = JAMA | volume = 208 | issue = 11 | pages = 2045–2050 | date = June 1969 | pmid = 5818983 | doi = 10.1001/jama.208.11.2045 }}</ref> and the lowest risk occurs with eye drops (affecting less than one in 224,716 prescriptions).<ref name="Lancaster1998"/>

===Bone marrow suppression===
Chloramphenicol may cause [[bone marrow suppression]] during treatment; this is a direct toxic effect of the drug on human [[mitochondria]].<ref name="pmid2486534">{{cite journal | vauthors = Yunis AA | title = Chloramphenicol toxicity: 25 years of research | journal = The American Journal of Medicine | volume = 87 | issue = 3N | pages = 44N–48N | date = September 1989 | pmid = 2486534 }}</ref> This effect manifests first as a fall in [[hemoglobin]] levels, which occurs quite predictably once a cumulative dose of 20&nbsp;g has been given. The anaemia is fully reversible once the drug is stopped and does not predict future development of aplastic anaemia. Studies in mice have suggested existing marrow damage may compound any marrow damage resulting from the toxic effects of chloramphenicol.<ref>{{cite journal | vauthors = Morley A, Trainor K, Remes J | title = Residual marrow damage: possible explanation for idiosyncrasy to chloramphenicol | journal = British Journal of Haematology | volume = 32 | issue = 4 | pages = 525–531 | date = April 1976 | pmid = 1259934 | doi = 10.1111/j.1365-2141.1976.tb00955.x | s2cid = 40234293 }}</ref>

===Leukemia===
Leukemia, a cancer of the blood or bone marrow, is characterized by an abnormal increase of immature white blood cells. The risk of childhood [[leukemia]] is increased, as demonstrated in a Chinese [[case–control study]],<ref>{{cite journal | vauthors = Shu XO, Gao YT, Linet MS, Brinton LA, Gao RN, Jin F, Fraumeni JF | title = Chloramphenicol use and childhood leukaemia in Shanghai | journal = Lancet | volume = 2 | issue = 8565 | pages = 934–937 | date = October 1987 | pmid = 2889862 | doi = 10.1016/S0140-6736(87)91420-6 | s2cid = 3217082 }}</ref> and the risk increases with length of treatment.

===Gray baby syndrome===
Intravenous chloramphenicol use has been associated with the so-called [[gray baby syndrome]].<!--
  --><ref name=McIntyre_2004>{{cite journal | vauthors = McIntyre J, Choonara I | title = Drug toxicity in the neonate | journal = Biology of the Neonate | volume = 86 | issue = 4 | pages = 218–221 | year = 2004 | pmid = 15249753 | doi = 10.1159/000079656 | s2cid = 29906856 }}</ref>
This phenomenon occurs in newborn infants because they do not yet have fully functional liver enzymes (i.e. UDP-glucuronyl transferase), so chloramphenicol remains unmetabolized in the body.<!--
  --><ref name="Piñeiro-Carrero_2004">{{cite journal | vauthors = Piñeiro-Carrero VM, Piñeiro EO | title = Liver | journal = Pediatrics | volume = 113 | issue = 4 Suppl | pages = 1097–1106 | date = April 2004 | pmid = 15060205 | doi = 10.1542/peds.113.S3.1097 | s2cid = 264867934 | url = http://pediatrics.aappublications.org/content/113/Supplement_3/1097.full.pdf | access-date = 2012-01-09 | url-status = live | archive-url = https://web.archive.org/web/20210828032546/https://pediatrics.aappublications.org/content/pediatrics/113/Supplement_3/1097.full.pdf | archive-date = 2021-08-28 }}</ref>
This causes several adverse effects, including [[hypotension]] and [[cyanosis]]. The condition can be prevented by using the drug at the recommended doses, and monitoring blood levels.<!--
  --><ref>{{cite journal | vauthors = Feder HM | title = Chloramphenicol: what we have learned in the last decade | journal = Southern Medical Journal | volume = 79 | issue = 9 | pages = 1129–1134 | date = September 1986 | pmid = 3529436 | doi = 10.1097/00007611-198609000-00022 }}</ref><!--
  --><ref>{{cite journal | vauthors = Mulhall A, de Louvois J, Hurley R | title = Chloramphenicol toxicity in neonates: its incidence and prevention | journal = British Medical Journal | volume = 287 | issue = 6403 | pages = 1424–1427 | date = November 1983 | pmid = 6416440 | pmc = 1549666 | doi = 10.1136/bmj.287.6403.1424 }}</ref><!--
  --><ref>{{cite journal | vauthors = Forster J, Hufschmidt C, Niederhoff H, Künzer W | title = [Need for the determination of chloramphenicol levels in the treatment of bacterial-purulent meningitis with chloramphenicol succinate in infants and small children] | language = de | journal = Monatsschrift Kinderheilkunde | volume = 133 | issue = 4 | pages = 209–213 | date = April 1985 | pmid = 4000136 }}</ref>

===Hypersensitivity reactions===
Fever, macular and vesicular rashes, angioedema, urticaria, and anaphylaxis may occur. [[Jarisch–Herxheimer reaction|Herxheimer's reactions]] have occurred during therapy for typhoid fever.<ref name="Drug Insert from DailyMed">{{cite web|title=Drug Insert from DailyMed|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=08c16a42-1ad4-400f-b1b0-75303eb86713|access-date=18 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140419012007/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=08c16a42-1ad4-400f-b1b0-75303eb86713|archive-date=19 April 2014}}</ref>

===Neurotoxic reactions===
Headache, mild depression, mental confusion, and delirium have been described in patients receiving chloramphenicol. [[Optic neuritis|Optic]] and peripheral [[neuritis]] have been reported, usually following long-term therapy. If this occurs, the drug should be promptly withdrawn.<ref name="Drug Insert from DailyMed" /> It is theorized that this is caused by chloramphenicol's effects on the metabolism of [[B vitamins|B-Vitamins]], specifically [[Vitamin B12|B-12.]]<ref>{{cite journal | vauthors = Ramilo O, Kinane BT, McCracken GH | title = Chloramphenicol neurotoxicity | language = en-US | journal = The Pediatric Infectious Disease Journal | volume = 7 | issue = 5 | pages = 358–359 | date = May 1988 | pmid = 3380586 | doi = 10.1097/00006454-198805000-00015 }}</ref>

===Myelodysplastic Syndrome===
Although rare, Chloramphenicol exposure is associated with some cases of [[Myelodysplastic syndrome|MDS]].  There is a report of a positive response to [[Immunosuppression|immunosuppressive treatment]].<ref>{{cite journal | vauthors = Arber C, Buser A, Heim D, Gratwohl A, Tichelli A, Passweg JR | title = Cyclosporine-responsive thrombocytopenia in a patient with chloramphenicol-associated myelodysplastic syndrome | language = en-US | journal =  Eur J Haematol | volume = 76 | issue = 3 | pages = 255–257 | date = March 2006 | pmid =  16451398 | doi = 10.1111/j.0902-4441.2005.00593.x}}</ref>