Drugs List

Therapeutic Indications

Uses

Life-threatening infections untreatable with less toxic antimicrobials
Meningitis caused by haemophilus influenzae: treatment
Typhoid: treatment

Administration

By intravenous injection or infusion, or by intramuscular injection. The powder must be reconstituted prior to use

Only 10% or lower concentrations may be used in neonates.
The 10% solution should be administered by intravenous injection over 1 minute, or in a larger volume of fluid by slow intravenous infusion.

Intravenous administration is preferable in order to achieve high blood levels quickly. Where intravenous administration is not possible, intramuscular administration may be used however absorption via this method is slow and unpredictable.

Contraindications

Acute porphyria
Breastfeeding
Pregnancy

Precautions and Warnings

Children under 4 years
Elderly
Premature infants
Hepatic impairment
Myelosuppression
Renal impairment

May impede development of immunity; do not use during active immunisation
Consult national/regional policy on the use of anti-infectives
Blood counts should be performed before and periodically during treatment
Monitor for signs of bone marrow depression
Monitor plasma concentrations of this drug
Consider pseudomembranous colitis if patient presents with diarrhoea
Superinfection may occur during therapy
Discontinue if haematological abnormalities develop
Avoid repeated or prolonged use

Chloramphenicol should never be used if a less toxic antibiotic is indicated. Sensitivity tests should be performed during therapy so that treatment can be switched as soon as possible when indicated.

Chloramphenicol may cause severe bone marrow depression which can lead to agranulocytosis, thrombocytopenic purpura or aplastic anaemia. High doses, prolonged administration or repeated courses are usually associated with these effects but they may also occur at relatively low doses.

Blood tests should be performed before and periodically during treatment. If any haemopoietic adverse effect is noted, treatment should be discontinued immediately. These determinations cannot be used to detect bone marrow depression.

Plasma concentrations of chloramphenicol should be monitored, especially in neonates and premature infants, children under 4 years, in the elderly, in patients with renal or hepatic impairment and in those receiving concurrent drugs that may interact with chloramphenicol. Recommended peak plasma concentrations determined approximately 1 hour after intravenous administration should be 10 to 25 mg/litre. Pre-dose trough concentrations should not exceed 15 mg/litre.

Use in Porphyria

Chloramphenicol has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

Pregnancy and Lactation

Pregnancy

Chloramphenicol is contraindicated in pregnancy.

Schaefer suggests that chloramphenicol is relatively toxic, and can cause severe agranulocytosis. If systemic use is justified before birth, the newborn should be observed for toxic symptoms. Briggs suggest that chloramphenicol may be used in pregnancy with caution although notes that because of the risk of grey syndrome it is contraindicated by other sources.

Chloramphenicol is known to cross the placenta, and can reach therapeutic concentrations in the foetus. There is, however, no evidence that chloramphenicol increases the incidence of congenital malformations. Despite this, chloramphenicol should not be used in the last trimester of pregnancy due to inadequate metabolism of the drug in the neonate; toxic concentrations can be reached which may cause the 'grey baby syndrome', which can be fatal.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Chloramphenicol is contraindicated in breastfeeding.

The Drugs and Lactation Database (LactMed) suggests that an alternative antibiotic is used, however if the use of chloramphenicol is unavoidable, monitoring of the infant's complete blood count and differential is advised. Hale suggests milks levels are too low to cause toxicity in infants however chloramphenicol is generally contraindicated in breastfeeding.

Chloramphenicol is excreted in breast milk, and may cause bone-marrow toxicity in the infant. The concentration of chloramphenicol in the breast milk is however usually insufficient to cause grey syndrome in the neonate. Other potential concerns involve the modification of the bowel flora in the infant, vomiting, refusal of the breast, excessive intestinal gas, allergic sensitisation to subsequent exposures, and somnolence.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agranulocytosis
Aplastic anaemia
Blood disorders
Blurred vision
Bone marrow depression
Depression
Diarrhoea
Dry mouth
Grey syndrome
Headache
Leukaemia
Loss of vision(transient)
Nausea
Optic neuritis
Peripheral neuritis
Superinfections
Thrombocytopenic purpura
Urticaria
Vomiting

Presentation

Powder for solution for injection containing chloramphenicol as chloramphenicol sodium succinate

Drugs List

Therapeutic Indications

Uses

Life-threatening infections untreatable with less toxic antimicrobials
Meningitis caused by haemophilus influenzae: treatment
Typhoid: treatment

Dosage

Plasma concentrations of chloramphenicol should be monitored, especially in neonates and premature infants, children under 4 years old, in the elderly, in patients with renal or hepatic impairment and in those receiving concurrent drugs that may interact with chloramphenicol.
Peak plasma concentration is 10mg/litre to 25mg/litre, measured two hours after intravenous administration. Pre-dose trough concentration should not exceed 15mg/litre.

Adults

Children

Neonates

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

By intravenous injection or infusion, or by intramuscular injection. The powder must be reconstituted prior to use

Only 10% or lower concentrations may be used in neonates.
The 10% solution should be administered by intravenous injection over 1 minute, or in a larger volume of fluid by slow intravenous infusion.

Intravenous administration is preferable in order to achieve high blood levels quickly. Where intravenous administration is not possible, intramuscular administration may be used however absorption via this method is slow and unpredictable.

Contraindications

Acute porphyria
Breastfeeding
Pregnancy

Precautions and Warnings

Children under 4 years
Elderly
Premature infants
Hepatic impairment
Myelosuppression
Renal impairment

May impede development of immunity; do not use during active immunisation
Consult national/regional policy on the use of anti-infectives
Blood counts should be performed before and periodically during treatment
Monitor for signs of bone marrow depression
Monitor plasma concentrations of this drug
Consider pseudomembranous colitis if patient presents with diarrhoea
Superinfection may occur during therapy
Discontinue if haematological abnormalities develop
Avoid repeated or prolonged use

Chloramphenicol should never be used if a less toxic antibiotic is indicated. Sensitivity tests should be performed during therapy so that treatment can be switched as soon as possible when indicated.

Chloramphenicol may cause severe bone marrow depression which can lead to agranulocytosis, thrombocytopenic purpura or aplastic anaemia. High doses, prolonged administration or repeated courses are usually associated with these effects but they may also occur at relatively low doses.

Blood tests should be performed before and periodically during treatment. If any haemopoietic adverse effect is noted, treatment should be discontinued immediately. These determinations cannot be used to detect bone marrow depression.

Plasma concentrations of chloramphenicol should be monitored, especially in neonates and premature infants, children under 4 years, in the elderly, in patients with renal or hepatic impairment and in those receiving concurrent drugs that may interact with chloramphenicol. Recommended peak plasma concentrations determined approximately 1 hour after intravenous administration should be 10 to 25 mg/litre. Pre-dose trough concentrations should not exceed 15 mg/litre.

Use in Porphyria

Chloramphenicol has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

Pregnancy and Lactation

Pregnancy

Chloramphenicol is contraindicated in pregnancy.

Schaefer suggests that chloramphenicol is relatively toxic, and can cause severe agranulocytosis. If systemic use is justified before birth, the newborn should be observed for toxic symptoms. Briggs suggest that chloramphenicol may be used in pregnancy with caution although notes that because of the risk of grey syndrome it is contraindicated by other sources.

Chloramphenicol is known to cross the placenta, and can reach therapeutic concentrations in the foetus. There is, however, no evidence that chloramphenicol increases the incidence of congenital malformations. Despite this, chloramphenicol should not be used in the last trimester of pregnancy due to inadequate metabolism of the drug in the neonate; toxic concentrations can be reached which may cause the 'grey baby syndrome', which can be fatal.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Chloramphenicol is contraindicated in breastfeeding.

The Drugs and Lactation Database (LactMed) suggests that an alternative antibiotic is used, however if the use of chloramphenicol is unavoidable, monitoring of the infant's complete blood count and differential is advised. Hale suggests milks levels are too low to cause toxicity in infants however chloramphenicol is generally contraindicated in breastfeeding.

Chloramphenicol is excreted in breast milk, and may cause bone-marrow toxicity in the infant. The concentration of chloramphenicol in the breast milk is however usually insufficient to cause grey syndrome in the neonate. Other potential concerns involve the modification of the bowel flora in the infant, vomiting, refusal of the breast, excessive intestinal gas, allergic sensitisation to subsequent exposures, and somnolence.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agranulocytosis
Aplastic anaemia
Blood disorders
Blurred vision
Bone marrow depression
Depression
Diarrhoea
Dry mouth
Grey syndrome
Headache
Leukaemia
Loss of vision(transient)
Nausea
Optic neuritis
Peripheral neuritis
Superinfections
Thrombocytopenic purpura
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mother's Milk, 13th edition (2008) Hale, T.W. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Chloramphenicol 1 g powder for injection. Essential Pharma Ltd. Revised October 2016.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 22 June 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Chloramphenicol. Last revised: March 31, 2010
Last accessed: July 27, 2010