Chloramphenicol

S01A - Antiinfectives ATC S01CA01 Small molecule approved 1950 Oral Parenteral Topical Natural product Withdrawn Black-box warning

JFDA label: Phenidexoline

⚠ Black-Box Warning

Blood dyscrasias:

Mechanism of Action

Inhibitor of Bacterial 70S ribosome — Bacterial 70S ribosome inhibitor

Target	Action	Gene / class
Bacterial 70S ribosome efficacy	INHIBITOR

Indications

Approved

Serious infections

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16.

Bacteria

Organism	Activity	MIC
Haemophilus influenzae	Susceptible	2.0 mg/L
Neisseria meningitidis	Susceptible	2.0 mg/L

Contraindications

Source: Lexicomp

Hypersensitivity to chloramphenicol or any component of the formulation Absolute
bacterial prophylaxis Absolute
treatment of trivial or viral infections Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (4)

Not Known Confusion · delirium · depression · headache

Blood and lymphatic system disorders (6)

Not Known Aplastic anemia · bone marrow depression · granulocytopenia · hypoplastic anemia · pancytopenia · thrombocytopenia

Immune system disorders (3)

Not Known Anaphylaxis · angioedema · hypersensitivity reaction

Gastrointestinal disorders (6)

Not Known Diarrhea · enterocolitis · glossitis · nausea · stomatitis · vomiting

Skin and subcutaneous tissue disorders (2)

Not Known Skin rash · urticaria

Eye disorders (1)

Not Known Optic neuritis

General disorders and administration site conditions (2)

Not Known Drug toxicity (Gray syndrome) · fever

Dosing

Source: Lexicomp

Serious infections: IV: 50 to 100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day (Moffa 2015).

(For additional information see "Chloramphenicol: Pediatric drug information") Serious infections: Infants, Children, and Adolescents: IV: Manufacturer’s labeling: 50 mg/kg/day in divided doses every 6 hours; severe infections (eg, bacteremia, meningitis) may require up to 100 mg/kg/day; decrease to 50 mg/kg/day as soon as possible. Note: In infants and children with suspected immature metabolic function, dose may be initiated at 25 mg/kg/day Alternative dosing: 50 to 100 mg/kg/day in divided doses every 6 hours; maximum daily dose: 4 g/day (Red Book [AAP] 2015)

Refer to adult dosing.

There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be necessary. Use with caution; monitor serum concentrations.

There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustments may be necessary. Use with caution; monitor serum concentrations.

Warnings & Precautions

Source: Lexicomp

Blood dyscrasias

Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) have occurred after both short-term and prolonged therapy; do not use for minor infections or when less potentially toxic agents are effective. Monitor CBC frequently in all patients; discontinue if evidence of myelosuppression. Irreversible bone marrow suppression may occur weeks or months after therapy. Avoid prolonged or repeated courses of treatment.

Gray syndrome

Characterized by cyanosis, abdominal distention, vasomotor collapse (often with irregular respiration), and death. Reaction appears to be associated with serum levels ≥50 mcg/mL (Powell 1982).

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Hepatic impairment

Use with caution; reduced dosage and serum concentration monitoring is recommended.

Renal impairment

Use with caution; reduced dosage and serum concentration monitoring is recommended. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Glucose 6-phosphate dehydrogenase deficiency

Use with caution in patients with glucose 6-phosphate dehydrogenase deficiency.

Neonates

Use in premature and full-term neonates and infants has resulted in “gray syndrome" characterized by cyanosis, abdominal distention (with or without emesis), vasomotor collapse (often with irregular respiration), and death; progression of symptoms is rapid; prompt termination of therapy required. Reaction may result from drug accumulation caused by immature hepatic or renal function in neonates and infants.

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

Animal reproduction studies have not been conducted. Chloramphenicol crosses the placenta producing cord concentrations approaching maternal serum concentrations. An increased risk of teratogenic effects has not been associated with the use of chloramphenicol in pregnancy (Czeizel 2000; Heinonen 1977). "Gray Syndrome" has occurred in premature infants and newborns receiving chloramphenicol. Chloramphenicol may be used as an alternative agent for the treatment of Rocky Mountain spotted fever in pregnant women although caution should be used when administration occurs during the third trimester (CDC [Biggs 2016]).

Lactation

Chloramphenicol and its inactive metabolites are present in breast milk. Chloramphenicol is well absorbed following oral administration; however, metabolism and excretion are highly variable in infants and children. The half-life is also significantly prolonged in low birth weight infants (Powell 1982). Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, taking into a

LactMed: monitor the infant.

Monitoring

Clinical pearl	CBC with differential (baseline and every 2 days during therapy), periodic hepatic and renal function tests, serum drug concentration

Chemistry & Properties

Formula	C11H12Cl2N2O5
Molecular weight	323.13 g/mol
IUPAC name	2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide
CAS	56-75-7
PubChem CID	5959
InChIKey	`WIIZWVCIJKGZOK-RKDXNWHRSA-N`
logP	0.91 (XLogP 1.1)
Polar surface area	112.7 Å²
H-bond acceptors / donors	5 / 3
Drug-likeness (QED)	0.41
Lipinski violations	0

SMILES

O=C(N[C@H](CO)[C@H](O)c1ccc([N+](=O)[O-])cc1)C(Cl)Cl

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.734 h
Volume of distribution	0.952 L/kg
Protein binding	59.9%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP3A4	Inhibitor	Ki 10.600000000000003 µM

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OAT1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Avapritinib	major
Benzhydrocodone	major
Brigatinib	major
Butorphanol	major
Cisapride	major
Cladribine	major
Clozapine	major
Deferiprone	major
Encorafenib	major
Entrectinib	major
Everolimus	major
Flibanserin	major
Guanfacine	major
Hydrocodone	major
Ivacaftor	major
Lemborexant	major
Levacetylmethadol	major
Lomitapide	major
Lonafarnib	major
Lurbinectedin	major
Naloxegol	major
Neratinib	major
Oliceridine	major
Oxycodone	major
Pemigatinib	major
Pexidartinib	major
Pimozide	major
Selpercatinib	major
Selumetinib	major
Siponimod	major
Tazemetostat	major
Typhoid vaccine (live)	major
Vibrio cholerae CVD 103-HgR strain live antigen (live)	major
Abemaciclib	moderate
Acalabrutinib	moderate
Acetohexamide	moderate
Adalimumab	moderate
Aflibercept	moderate
Aldesleukin	moderate
Alemtuzumab	moderate

Showing 40 of 100+.

Registered Products (8)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Iso Miphenicol	Solution 0.5 %	10 ml	Petra Drug Store	0.360
Chloramphenicol E/D	Ophthalmic Solution 0.5 %	10 ml	AL Razi Drug Store	0.840
Phenicol 0.5% Eye Drops	Ophthalmic Solution 5 mg/ml	10 ml	Amman Pharmaceutical Indusries	1.010
Chloroptic E/D	Ophthalmic Solution 0.5 %	10 ml	Arab Company for Medical & Agricultural Products	1.180
Phenicol eye ointment	Ointment 1 %	5 g tube	Amman Pharmaceutical Industries Co	1.250
Otocol ear drops	Eye/Ear Drops 50 mg, 50 mg	10 ml	Amman Pharmaceutical Indusries	1.430
Phenidex eye drops	Ophthalmic Solution 0.5 %, 0.1 %	10 ml	Amman Pharmaceutical Indusries	1.840
Phenidexoline	Solution 0.5 %, 0.025 %, 0.1 %	10 ml	Amman Pharmaceutical Industries Co	2.210