Interacting drugs - summary

+ Chloramphenicol

Barbiturate +  Chloramphenicol
decreased chloramphenicol serum levels occur   

Chloramphenicol + Barbiturate
 resulting in clearance decreased, resulting in increased levels of toxicity      

Rifampicin  +  Chloramphenicol  
 concomitant administration reduce serum chloramphenicol  levels,
                  

Chloramphenicol + anticoagulants
  anticoagulant action enhanced     
 

Chloramphenicol  + cyclophosphamide
 decreased or delayed activation of cyclophosphamide occur,
 

Chloramphenicol   Hydantoin
Hydantoin + Chloramphenicol
 serum hydantoin levels increased , possibly resulting in toxicity.        
  In addition  chloramphenicol levels  increased or decreased

Chloramphenicol + Iron salts
 serum iron levels increased

Chloramphenicol +    Penicillins
 synergistic efectsdevelop in the treatment of certain microorganisms,
   but antagonism may also occur                    

Chloramphenicol + sulfonylureas 
  clinical manifestastions of hypoglycemia  occur with concurrent use
 

Vitamin B12  
 hematologic effects of Vitamin B12 decreased in patients with
  pernicious anemia by concurrent chloramphenicol

Zalcitabine 
these drugs are associated with peripheral neuropathy
 Avoid concomittant use when possible     
     
Tetanus toxoid
systemic chloramphenicol impair amnestic response to tetanus
 toxoid. Avoid concurrent use.

Serious infections for which less potentially dangerous drugs are ineffective.

Hemotologic-

Most serious adverse effect is bone marrow suppression and aplastic anaemia, irreversible in some cases. Neutropenia and Thrombocytopenia.

Hemoglobinuria-

Paroxymal nocturnal hemoglobinuria has been reported

GI-

Nausea, vomting, glossitis, stomatitis, diarrhea, enterocolitis (low incidence)

CNS-

Headache and mild depression, mental confusion, delirium. Optic and peripheral neurotis have been reported, usually following long-term therapy. If this occurs promptly withdraw the drug.

Hypersensitivity- Fever, macular and vesicular rashes, angioedema, urticaria, anaphylaxis. Herxheimer reactions have occured during therapy for typhoid fever. Grey baby syndrome Toxic reactions including fatalities (aapproximately (40%) have occurred in the premature infant and newborn.

The signs and symptoms associated with these reactions have been referred to as the -grey syndrome and these are- * In most cases therapy was insituted within the first 48 hours.

* Symptoms first appeared after 3 to 4 days of treatment with high doses.

* Symptoms appeared in the following order- abdominaldistentiuonwith or without emesis, progressive palid cyanosis, vasmotor collapse, frequently accompanied by irregular respiration, death within few hours of onset.

* Progress of symptoms was accelrated with higher doses.

* serum levels studies revealed unusually high drug concentrations.

* terminaton of theapy upon early evidence of associated symptoms frequently reversed the process with complete recovery.

* prexisting liver dysfunction may be significant risk factor. Interferes with determination of serum proteins.

BUN, urine, sugar.

Topical application to eye:

Hypersensitivity reaction including rashes, fever and angioedema. Very rarely aplastic anaemia.

Eye drops: Ototoxicity.

History of sensitivity & or toxic reaction. Lactation, pregnancy.

Special precautions:

Hematology-

Evaluate baseline and periodic blood studies every 2 days during therapy.

Discontinue the drug upon appearanace of reticulocytopenia,leukopenia, thrombocytopenia, anemia or any other findings attributable to chloramphenicol. Such studies do not exclude the possible appearanace of the irrvesible chloramphenicol type bone marrow depression.

Avoid concurrent therapy with other drugs tht amay cause bone marrow depression. Avoid repeated course if at all possoble.

Do not continue treatment longer than required to produce a cure.

Acute intermittant porphria- or glucose phosphate dehydrodenase deficiency (G6PD - Use with caution in patients with these conditions.

Superinfection: Use of antibiotics especially over a prolonged or repeated therapy may result in bacterial or fungal overgrowth of susecptible organisms. such overgrowth may lead to secondary infection. Take appropiate measures if this occurs.

Warnings

Blood dyscrasis- Serious and fatal blood dyscrasias (plastic anemia, hypoplastic anemia, thrombocytopenia and granulocytopenia) occur.

An irreversble type of bone marrow depression leading to aplastic anemia with a high rate of mortality is characterrized by appearance of bone marrow aplasia or hypoplasia weeks or months after therapy.

Peripherally pancytopenia is most often observed but only one or two of the three major cell types (erythrocytes, leukocytes and platelets ) may be depressed.

Several cases of aplastic anemia have been associated with chloramphenicol opthalmic ointment.

Renal/hepatic function impairment- excessive blood levels may result from use of the recommended dose in patients with impaired liver or kidney function including that due to immature metabolic processes in the infant,

Adjust the dosage accordingly or determine the blood concentration at appropiate intervals.

Pregnancy- Since it readily crosses the placental barrier, cautious use is particularly important during pregnancy at term or during labor because of potential toxic effects on the fetus.(gray syndrome)

Lactation- Use with caution, if at all during lactaion, because of the possbile toxic effect on the nursing infant.

Children- Use with caution with reduced dosage in premature and full term infants to avoid gray syndrome toxicity. Monitor drug serum levels carefullly during therapy of the new born.

Indications:

Serious infections for which less potentially dangerous drugs are ineffective.

Acute infections caused by Stap Typhi- Chloramphenicol is the drug of choice. In treatment of typhoid fever, some authorities recommended that chloramphenicol be used at therapeutic levels for 8 to 10 day afer the patient becomes afebrile, to lessen the possibility of relapse

Dosage:

Adults- 50mg/kg/day in divided doses every 6 hours for typhoid fever and rickettisial infections. Exceptional infections due to moderately resistent organisms, may require dosage upto 100mg/kg/day.

Children- 50 to 75mg/kg/day in divided doses every 6 hours recommended for most infections.

For meningitis- 50 to 100mg/kg/day in divided doses every 6 hours,has been recommended. .

New borns- 25mg/kg/day in 4doses every 6 hours usually produces and maintains adequate concentration in blood and tissues after first 2 weeks of life.

Full term infants ordinarily may receive upto 50mg/kg/day in 4doses every 6 hours..

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

For Availability/supplies 

Pancytopenia ( aplastic anemia ) 

Severe anemia accompanied by fever, neutropenia, and bleeding. Post mosterm examination revealed a yellow, hypocellular bone marrow. The term aplastic anemia was applied to all patients with refractory and progressive pancytopenia until the advent of bone marrow examination in diagnostic purposes.

Drugs causing adverse reactions- 

1. Chloramphenicol

2. Phenytoin

3. Mephenytoin

4. Trimethadione

5. Phenylbutazone

6. Oxyphenbutazone

7. Gold salts

8. Mepacrine

9. Quinacrine

10. Potassium perchlorate

11. Cytotoxics

Pharmacology:

Chloramphenicol binds 50S ribosomal subunits of bacteria and interferes with or inhibits protein synthesis. In vitro, chloramphenicol exerts mainly a bacteriostatic effect on a wide range of gram -ve and gram +ve bacteria

Pharmacokinetics:

Chloramphenicol base is absorbed rapidly from the intestinal tract and is 75% to 90% bioavailable. Chloramphenicol diffuse rapidly and highest concentrations are found in liver and kidney, and lowest concentrations are found in brain and CNS fluid.

Take on an empty stomach 1 hr before or 2 hr after meals

Pregnancy:

There are no studies to establish the safety of this drug in pregnancy. Since it readily crosses the placentel barrier, cautious use is particularly important during pregnancy.

Lactation:

Chloramphenicol appears in breast milk with a milk:plasna ratio of 0.5. Use with caution, if at all during lactation.

Children:

Use with caution and in reduced dosage forms in pre-mature and full term infants to avoid gray syndrome toxicity.