Chloramphenicol Capsules Bp 250mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Chloramphenicol Capsules BP 250mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Chloramphenicol BP 250.0 mg
3. PHARMACEUTICAL FORM
Hard Gelatin Capsules
4. CLINICAL PARTICULARS
4.1. Therapeutic Indications
Typhoid fever and life threatening infections, particularly those caused by haemophilus influenzae, where other antibiotics will not suffice.
4.2. Posology and Method of Administration
Normal dose for adults and the elderly: 50mg / kg body weight daily in 4 divided doses. For severe infections (meningitis, septicaemia) this dose may be doubled initially, but it must be reduced as soon as clinically practical.
Not recommended for children
4.3 Contraindications
Known hypersensitivity or toxic reaction to chloramphenicol or to any of the excipients.
Chloramphenicol is contra-indicated in prophylaxis or treatment of minor infections; during active immunisation; and in porphyria patients.
Chloramphenicol is contra-indicated in patients taking drugs liable to depress bone marrow function (see section 4.5).
Chloramphenicol must not be used in breast-feeding mothers and during pregnancy or labour, due to a risk of foetal/ infant damage (Gray Baby syndrome).
4.4 Special warnings and precautions for use
Chloramphenicol should only be used if other treatments are ineffective and its use should always be carefully monitored.
Dose reduction and plasma level monitoring may be required in patients with hepatic or renal impairment; in the elderly; and in patients concurrently treated with interacting drugs. See section 4.5
Periodic blood testing should be conducted during prolonged or repeated treatment. Chloramphenicol should be discontinued if a significant detrimental effect is seen.
4.5 Interaction with other medicinal products and other forms of interaction
Warfarin, Phenytoin, Sulphonylureas, Tolbutamide:
Chloramphenicol prolongs the elimination, increasing the blood levels, of drugs including warfarin, phenytoin, sulphonylureas, tolbutamide.
Anticonvulsants and Anticoagulants:
Doses of anticonvulsants and anticoagulants may need to be adjusted if given concurrently.
Penicillins and Rifampicin
Complex effects (including reduced / increased plasma levels) requiring monitoring of chloramphenicol plasma levels have been reported with co-administration of penicillins and rifampicin.
Paracetamol:
Concurrent administration of paracetamol should be avoided as this prolongs chloramphenicol half-life.
Calcineurin Inhibitors (CNIs) Ciclosporin and Tacrolimus:
Treatment with chloramphenicol possibly increases the plasma levels of the CNIs ciclosporin and tacrolimus.
Barbiturates:
The metabolism of chloramphenicol is accelerated by barbiturates, such as phenobarbitone, leading to reduced plasma concentrations. There is a possible decrease in the metabolism of phenobarbitone with concomitant chloramphenicol administration.
Oestrogens:
There is a small risk that chloramphenicol may reduce the contraceptive effect of oestrogens.
Hydroxocobalamin:
Chloramphenicol reduces the response to hydroxocobalamin.
Drugs causing agranulocytosis:
Chloramphenicol is contra-indicated in patients taking drugs liable to suppress bone marrow function (see section 4.3). These include:
Carbamazapine Sulphonamides Phenylbutazone Penicillamine Cytotoxic agents
Some antipsychotics, including clozapine and particularly depot antipsychotics Procainamide
Nucleoside reverse transcriptase inhibitors Propylthiouracil
4.6. Pregnancy and Lactation
The use of chloramphenicol is contra-indicated as the drug crosses the placenta and is excreted in breast milk.
4.7 Effects on ability to drive and use machines
No significant effect on driving ability.
4.8 Undesirable effects
The most serious undesirable effects that may arise are:
Blood and lymphatic disorders
(i) A reversible dose related bone marrow depression.
(ii) An irreversible aplastic anaemia with an estimated frequency between 1/4000 & 1/100000.
Other undesirable effects (of unknown frequency) are:
Blood and the lymphatic system disorders Increase in bleeding time.
Immune system disorders
Hypersensitivity reactions including allergic skin reactions.
Eye disorders
Optic neuritis leading to blindness.
Ear and labyrinth disorders Ototoxicity.
Vascular disorders
Acidotic cardiovascular collapse.
Gastrointestinal disorders
Nausea, vomiting, glossitis, stomatitis, diarrhoea, enterocolitis.
Pregnancy, puerperium and perinatal conditions
“Gray” syndrome, particularly in the newborn, which appears to be related to excessively high plasma levels. The Gray baby syndrome consists of abdominal distension, pallid cyanosis, vomiting, progressing to vasomotor collapse, irregular respiration and death within a few hours of onset of symptoms. (These symptoms are thought to be dose related and rapid clearance of chloramphenicol has been associated with recovery).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Where adverse effects show signs of developing administration must be stopped immediately and treatment is mainly supportive. If an allergy develops, oral antihistamines may be used. In severe overdosage e.g. Gray Baby Syndrome, there is a need for a rapid reduction in plasma levels and it has been reported that resin haemoperfusion (XAD-4) substantially increases chloramphenicol clearance.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic Properties
Chloramphenicol is a broad spectrum antibiotic acting by interfering with bacterial protein synthesis.
The most important action on the body tissue is the adverse one of bone marrow depression. There is significant plasma protein binding and the drug is largely inactivated in the liver.
5.2. Pharmacokinetic Properties
Chloramphenicol is readily and rapidly absorbed from the G.I. tract. Particle size may affect rate of absorption, but will not affect total absorption. Significant serum levels observable 30 minutes after ingestion and half life may be 2 - 5 hours.
Chloramphenicol is widely distributed in body tissues and fluids. It is found in Cerebro-spinal fluid. It crosses the placental barrier and diffuses into breast milk.
There is significant plasma protein binding (up to 60%).
Excretion is mainly in the urine and largely inactivated in the liver.
5.3. Pre-clinical Safety Data
None
6. PHARMACEUTICAL PARTICULARS
6.1. List of Excipients
Sodium Lauryl Sulphate BP, Potato Starch BP, Magnesium Stearate BP, Talc BP, Gelatin BP and Titanium Dioxide BP (E171).
6.2. Incompatibilities
There are no significant incompatibilities with the product.
6.3 Shelf life
5 years
6.4. Special Precautions for Storage
Store in a cool dry place in the original package.
6.5. Nature and Contents of Container
The product is available in Securitainers in packs of 30, 50, 60, 100 & 1000 capsules. All containers are made up of a High Density Polypropylene body and a Low Density Polyethylene cap..
Instructions for Use/Handling
6.6.
Not applicable
7. MARKETING AUTHORISATION HOLDER
Chemidex Pharma Limited
T/A Essential Generics or Chemidex Generics
Egham Business Village,
Crabtree Road,
Egham Surrey TW20 8RB United Kingdom
8. MARKETING AUTHORISATION NUMBER
PL 17736/0075
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25th February 2005
10 DATE OF REVISION OF THE TEXT
16/10/2015