Metronidazole
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Brand names, Trade names |
| 1.6 Manufacturers, Importers |
| 1.7 Presentation, Formulation |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Properties of the substance |
| 3.3.1.1 Colour |
| 3.3.1.2 State/Form |
| 3.3.1.3 Description |
| 3.3.1 Properties of the locally available formulation(s) |
| 3.4 Other characteristics |
| 3.4.1 Shelf-life of the substance |
| 3.4.2 Shelf-life of locally available formulation(s) |
| 3.4.3 Storage conditions |
| 3.4.4 Bioavailability |
| 3.4.5 Specific properties and composition |
| 4. USES |
| 4.1 Indications |
| 4.1.1 Indications |
| 4.1.2 Description |
| 4.2 Therapeutic dosage |
| 4.2.1 Adults |
| 4.2.2 Children |
| 4.3 Contraindications |
| 5. ROUTES OF ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Other |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 7. PHARMACOLOGY AND TOXICOLOGY |
| 7.1 Mode of action |
| 7.1.1 Toxicodynamics |
| 7.1.2 Pharmacodynamics |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 7.7 Main adverse effects |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central nervous system (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ear, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Other |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Relevant laboratory analyses |
| 10.2.1 Sample collection |
| 10.2.2 Biomedical analysis |
| 10.2.3 Toxicological analysis |
| 10.2.4 Other investigations |
| 10.3 Life supportive procedures and symptomatic/specific treatment |
| 10.4 Decontamination |
| 10.5 Elimination |
| 10.6 Antidote treatment |
| 10.6.1 Adults |
| 10.6.2 Children |
| 10.7 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 11.2 Internally extracted data on cases |
| 11.3 Internal cases |
| 12. ADDITIONAL INFORMATION |
| 12.1 Availability of antidotes |
| 12.2 Specific preventive measures |
| 12.3 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
1. NAME
1.1 Substance
Metronidazole (INN)
(WHO, 1992)
1.2 Group
ATC classification index
Antibacterials for systemic use(J01)/
Other antibacterials (J01X)/
Imidazole derivatives (J01XD).
(WHO, 1992)
1.3 Synonyms
Metronidazolo
Bayer-5630
NSC-50364
RP-8823
SC-10295
(Reynolds, 1993; Budavari, 1989)
1.4 Identification numbers
1.4.1 CAS number
443-48-1
1.4.2 Other numbers
RTECS NI5600000
1.5 Brand names, Trade names
Monocomponent products
Worldwide Flagyl
Other names
Argentina Debretol, Nalox, Tranoxa, Tricofin
Australia Trichozole
Canada Neo-Tric, Novonidazol, Trikacide
Denmark Elyzol, Trichomal
Germany Clont, Fossyol, Krencosan, Rathimed N,
Sanatrichom, Trichos Cordes, Tricho-
Gynaedron oral
Hungary Klion
Italy Deflamon, Geneflavir, Tricocet, Trivazol,
Vagilen
Norway Elyzol
Poland Entizol
Spain Tricowas B
Sweden Elyzol
Switzerland Metrolag
Combination products
Entamizole D.S.
Dependal
(Reynolds, 1982)
(To be completed by each Centre using local data)
1.6 Manufacturers, Importers
May & Baker, Searle, Specia, Rhone-Poulenc, Boots
SK & F.
(To be completed by each Centre using local data)
1.7 Presentation, Formulation
Tablets, suspension and intravenous infusions
(previously vaginal pessaries, suppositories, intramuscular
injection)
Metronidazole tablets 200, 250, 400, 500 mg
Metronidazole injection 5 mg/mL, 100 and 300 mL
Metronidazole suppositories 0.5 and 1 g
Metronidazole vaginal ovule 500 mg.
Metronidazole suspension 200 mg/5 mL
(To be completed by each Centre using local data)
2. SUMMARY
2.1 Main risks and target organs
Gastrointestinal tract and nervous system are main
organs of toxicity (Roe, 1983).
2.2 Summary of clinical effects
Acute toxicity causes gastrointestinal tract symptoms.
Chronic toxicity causes neurological damage.
After oral or intravenous infusion the following effects can
occur:
Metallic taste in mouth, nausea, vomiting and anorexia.
Headache, dizziness, vertigo, syncope and even convulsive
seizure, and peripheral neuropathy.
2.3 Diagnosis
Clinical diagnosis is difficult to determine because of
the lack of history of toxic ingestions.
Laboratory analysis by HPLC should be considered for
information.
2.4 First aid measures and management principles
There is no specific antidote. Only symptomatic and
general supportive therapy is necessary.
Gastric lavage (preferably within 1 to 2 hours of the
ingestion)and activated charcoal after ingestion. At the
same time basic life support (airway, breathing and
circulation) must be maintained.
If convulsions occur give diazepam intravenously at 5 to 10
mg (0.04 mg/kg for children).
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Discovery of aomycin (nitro imidazole) in 1955 by
Nakumura and demonstration of its anti-protozoal properties
by Horie in 1956 led to chemical synthesis of nitro
imidazoles.
3.2 Chemical structure
Structural formula
Molecular formula
C6H9O3N3
Molecular weight
171.16
Chemical names
2-(2-Methyl-5-nitroimidazol-1-yl)ethanol
2-methyl-5-nitroimidazole-1-ethanol
1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole
1-( beta-ethylol)-2-methyl-5-nitro-3-azapyrrole
(Reynolds, 1993; Budavari, 1989)
3.3 Physical properties
3.3.1 Properties of the substance
3.3.1.1 Colour
Pale yellow; darkens on exposure
to light.
3.3.1.2 State/Form
Crystalline powder
3.3.1.3 Description
Slightly soluble in water, in
alcohol, in acetone or in methylene
chloride; very slightly soluble in
ether.
pH of a saturated aqueous solution at 20°C
is about 6.5.
Melting point 160°C
(Reynolds, 1993; Budavari, 1989)
3.3.1 Properties of the locally available formulation(s)
To be completed by each Centre using local
data.
3.4 Other characteristics
3.4.1 Shelf-life of the substance
Injection 3 years.
Tablets 5 years
Suspension 2 years
Intravenous pre-mixed2 years
infusions
3.4.2 Shelf-life of locally available formulation(s)
To be completed by each Centre using local
data.
3.4.3 Storage conditions
Protect from direct sunlight, infusions to be
kept between 15 to 30°C.
3.4.4 Bioavailability
Bioavailability of oral tablets is 93% to 95%.
Not affected by food or drink. (Ralph, 1983)
3.4.5 Specific properties and composition
Metronidazole benzoate is used for the
suspension form of metronidazole.
Metronidazole hydrochloride is used for the
intravenous form of metronidazole.
(Reynolds, 1993)
4. USES
4.1 Indications
4.1.1 Indications
Protozoal infections
Balantidium coli; Blastocystis hominis; Entamoeba
histolytica; Giardia intestinalis (Giardia lamblia);
and Trichomonas vaginalis.
Obligate anaerobic bacteria infections
Bacteroides spp and Clostridium spp (including C.
difficile, the causative organisms in
pseudomembranous colitis).
Infections
Campylobacter spp; Gardnerella vaginalis (which
causes bacterial vaginitis); Oral bacteria (Vincent's
gingivitis).
Amoebiasis
Intestinal and extra-intestinal, including amoebic
liver abscess
Other
Fascialiasism, Guinea-worm infection, Leishmaniasia,
Mononucleosis, Tropica eosinophilia, Vaginitis
(Gardnerella vaginalis), Vincent's infection.
Trichomonas vaginalis, both symptomatic and
carriers.
Anaerobic gram negative bacilli = Bacteroides
fragilis group, Fusobacterium species.
Anaerobic gram positive bacilli = Clostridium spp
susceptible strains of Eubacterium.
Anaerobic gram positive cocci = Peptococcus spp.
Peptostreptococcus spp.
4.1.2 Description
Not relevant.
4.2 Therapeutic dosage
4.2.1 Adults
Oral
Amoebiasis (Acute amoebic dysentery)
400 to 800 mg 3 times daily for 5 to 10 days.
Amoebiasis (Amoebic liver abscess)
400 to 800 mg 3 times daily for 5 to 10 days.
Trichomoniasis
2 g in single dose; or
250 mg 3 times daily for 5 to 7 days; or
400 mg twice a day; or
800 mg in the morning and 1200 mg at night, for 2
days.
Anaerobic infections
800 mg initial dose, followed by 400 mg every 8
hours, for about 7 days.
Giardiasis
2 g daily as a single dose for 3 days.
Parenteral
Anaerobic infections
500 mg as intravenous infusion every 8 hours.
Rectal
Anaerobic infections
1 g suppository every 8 hours for 3 days, then every
12 hours.
(Reynolds, 1993)
4.2.2 Children
Oral
Amoebiasis (Acute amoebic dysentery)
35 to 50 mg/kg daily in divided doses is
recommended.
Amoebiasis (Amoebic liver abscess)
35 to 50 mg/kg daily in divided doses has been
recommended.
Trichomoniasis
15 mg/kg daily in divided doses for 7 days has been
recommended.
Anaerobic infections
7.5 mg/kg every 8 hours.
Giardiasis
15 mg/kg daily in divided doses has been recommended
for 3 days.
Parenteral
Anaerobic infections
7.5 mg/kg as intravenous infusion every 8 hours.
Rectal
Anaerobic infections
7.5 mg/kg every 8 hours for 3 days, then every 12
hours.
(Reynolds, 1993)
4.3 Contraindications
Not for use in persons with prior history of
hypersensitivity to nitroimidazole derivatives or
metronidazole preparation.
It is contraindicated in trichonosomiasis in the first
trimester of pregnancy. Avoid use during breast-feeding
because metronidazole is excreted in breast milk. Nursing
should be discontinued during therapy and for two days
following metronidazole therapy.
It should be used with caution in cases with CNS diseases and
should be discontinued immediately if abnormal neurological
signs develop during treatment.
5. ROUTES OF ENTRY
5.1 Oral
It is the most frequent route of intoxication.
5.2 Inhalation
Not relevant.
5.3 Dermal
Not relevant.
5.4 Eye
Not relevant.
5.5 Parenteral
Intoxication after parenteral route is rare.
5.6 Other
No cases reported arising from rectal or vaginal
administration.
6. KINETICS
6.1 Absorption by route of exposure
Oral
Metronidazole is readily and almost completely absorbed from
the gastrointestinal tract (Reynolds, 1989). Bioavailability
is nearly 100%. Maximum concentrations occur in the serum
after about one hour and traces are detected after 24 hours
(Bergan et al., 1984; McGilveray, et al., 1978; Ralph,
1983).
It is well absorbed after oral administration. Following
ingestion of a 250 mg, 500 mg or 2000 mg dose of
metronidazole in healthy fasting adults peak plasma levels
are reached within one to three hours and average 4.6 to 6.5
micrograms/mL, 11.5 to 13 micrograms/mL and 30 to 45
micrograms/mL, respectively (McEvoy, 1995).
Rectal
Metronidazole is readily and almost completely absorbed from
the rectal mucosa (Reynolds, 1989).It is absorbed more slowly
after rectal administration than after oral dosing, with a
peak concentration at about four hours. Bioavailability by
this route is about 70%.
6.2 Distribution by route of exposure
The apparent volume of distribution is 0.6 to 0.8 L/kg;
after 400 mg intravenously, it is 1.05 l/kg (Jensen & Gugler,
1983; Gupte, 1983).
Protein binding is low, between 8 and 11% (Schwartz & Jeunet,
1976).
It also penetrates well in body tissue and fluids including
vaginal secretions, seminal fluid, saliva and breast milk,
and therapeutic concentration has been achieved in
cerebrospinal fluid (Schwartz & Jeunet, 1976).
As compared to serum concentration, the following tissue
concentrations are observed:
Middle ear mucosa 180%
Gall bladder bile 135%
CSF 120%
Abdominal muscles 110%
Fallopian tube 100%
Uterus 95%
Human milk 90%
Ileum 85%
Bone 80%
Colon 70%
Peritoneal cavity, appendix and choledochus bile 55% but
omentum has only 20% and subcutaneous tissue 10%.
(Houghton et al.,1979)
When given an oral suspension of benzoyl metronidazole, the
system availability is 80% of metronidazole.
When given as suppository, the bioavailability is between 44
to 80% and a mean 67% of oral dose (Bergan et al.,
1984).
6.3 Biological half-life by route of exposure
Elimination half-life after an intravenous infusion of
1.5 g is between 6.6 to 10.3 hours, with a mean of 8.4 hours.
The half-life of hydroxy metabolites is between 13.3 and 19.1
hours (Bergan et al., 1984). Repeated doses every 6 to 8
hours may result in some accumulation.
In cases of impaired liver function, elimination is slower.
In renal failure half-life of metronidazole is unchanged but
that of metabolites is increased.
6.4 Metabolism
Metronidazole is almost completely metabolized in liver.
Principal metabolites result from oxidation of side chain and
formation of glucuronides. A small amount of reduced
metabolites, including ring cleavage products, is formed by
gut flora (Koch et al., 1981).
Major metabolites are 1-(2 hydroxy-ethyl)-2-hydroxy methyl-5-
nitroimidazole which is active and which gives advantage in
terms of length of action, and the inactive 1-acetic acid-2-
methyl-5-nitroimadozole.
6.5 Elimination by route of exposure
Main route of elimination is by kidney but it is also
secreted in bile and breast milk. 77% is recovered from
urine and 14% from stool (Gray et al., 1961).
Urine of some patients may become reddish-brown due to some
unidentified pigment derived from this drug.
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
It is basically a safe drug and has no direct
effects on mammalian cells which have aerobic
metabolism. In a few patients given very high
intravenous doses of metronidazole as an adjunct to
radiotherapy (Mahad & Wilson, 1981) epileptiform
seizures have been reported due to its direct effects
on CNS.
7.1.2 Pharmacodynamics
Metronidazole is an anti-pathogen with
selective toxicity to micro-aerophilic, anaerobic and
hypoxic/anoxic cells. Therefore its pharmacodynamic
actions are not relevant to toxicity in man.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Metronidazole has a very high
margin of safety. No lethal dose has been
described in humans as yet.
7.2.1.2 Children
Metronidazole has a very high
margin of safety. No lethal dose has been
described in humans as yet.
7.2.2 Relevant animal data
LD50 oral (rats) 1 to 5 g/kg.
LD50 oral (mice) 1 to 5 g/kg.
No serious toxicity has been reported in rats dosed
at 150 mg/kg/day, dogs at 50 to 75 mg/kg/day or
monkeys at 225 mg/kg/day (Roe, 1983).
Promotion of pulmonary tumour at a very high level in
the mouse (500 mg/kg/day), produced a statistically
significant increase in live tumours. Two lifetime
studies in hamsters were negative.
In higher doses, testicular dystrophy and
prostatiatrophy have been reported in rats and dogs
which showed ataxia, muscular atrophy and
tremors.
In long-term toxicity studies involving rats for 2
years (normal life span) high doses have been given
and the results have been conflicting. Cohen (1973)
reported no increase in tumour incidence, while
Rustia & Shubik (1972) found increased incidence of
tumours in male mice, female mice showed increased
incidence of lung tumour, but absolute incidence was
actually less than male mice controls. Female mice
also had lymphomas more often when given two higher
doses.
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
No data is available in humans. Studies in mice and
rats reported. Carcinogenic in rodents after high oral dose
(Voogel, 1981).
7.4 Teratogenicity
It crosses the placental barrier and enters fetal
circulation. Studies in rats in doses up to 5 times human
doses have not reported any harm to foetuses.
Although metronidazole has been given in all the stages of
pregnancy orally no adverse report has been received.
However, it is not recommended for use in first trimester of
pregnancy.
In nursing mothers and neonates there have not been any well
controlled studies, but because it appears in breast milk in
concentration similar to serum, it should not be used except
for amoebiasis.
7.5 Mutagenicity
Metronidazole is mutagenic in rodents in high doses for
prolonged periods. It is also mutagenic in bacteria (Voogde,
1981).
Mutagenic activity associated with metronidazole has been
reported in the urine of patients receiving therapeutic
doses.
7.6 Interactions
Metronidazole has disulfiram-like action and patients
reported abdominal distress, nausea, vomiting, flushing,
headache and abdominal distress if they drank alcohol during
treatment. Confusional and psychotic states have developed
when disulfiram and metronidazole are used together.
Intravenous "flagyl" infusion is incompatible with
cefamandole naftate, cefoxitin sodium, penicilllin potassium
(Olsen & Hebjorn, 1982), dextrose 10%, Hartmann solution,
hydrocortisone/sodium succinate.
Use of liver microsomal enzyme inducers like phenobarbitone
and phenytoin has resulted in reducing the half-life and
increasing the metabolism of metronidazole. While drugs like
cimetidine which decrease liver microsomal enzyme activity
result in prolongation of half-life and decrease plasma
clearance of metronidazole. Metronidazole is also reported to
potentiate the anticoagulant action of coumarin
anticoagulants leading to prolonged prothrombin time.
Laboratory test interactions
Metronidazole may interfere with certain types of
determination of serum chemistry values such as aspartate
aminotransferase. Alanine aminotransferase, lactic
dehydrogenase, triglycerides and hexokinase glucose. All
these involve enzymatic coupling of the assay to oxidation-
reduction of nicotine adenine dinucleotide (NAD+ -> - NADH).
It is due to similarity in absorbance peaks of NADH (340 nm)
and metronidazole (322 nm) at pH 7.
7.7 Main adverse effects
The two serious side effects of metronidazole are
convulsive seizure and peripheral neuropathy, characterized
by numbness and paraesthesia of the extremities.
Dizziness, vertigo, incoordination, ataxia, irritability,
depression, weakness and insomnia.
Gastrointestinal disturbances include nausea, vomiting,
anorexia, diarrhoea, epigastric distress and abdominal
cramping. Constipation has also been reported.
In the mouth a sharp metallic unpleasant taste, furry tongue,
glossitis and stomatitis have been reported with a sudden
overgrowth of candida.
Metronidazole and related chemicals have caused blood
dyscrasias, and temporary neutropenia has been reported after
metronidazole, which reverses after therapy. Rarely
thrombocytopenia.
Cardiovascular-flattening of the T waves may be seen in ECG
tracing.
Hypersensitivity - urticaria, erythematous rash, flushing,
nasal congestion, dryness of mouth, vulva and vagina and
fever.
Renal - dysuria, cystitis, polyuria, incontinence and a sense
of pelvic pressure. Instances of darkened urine are due to
unknown metabolites of metronidazole which have no clinical
significance. Other - proliferation of candida in vagina,
dyspareunia, decrease of libido, proctitis and fleeting joint
pains.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
This Section (appears/will appear in future) at the end of
this PIM in the form of an appendix (Appendix 1).
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Single oral doses of metronidazole, up to 15
g, have been reported in suicide attempts and
accidental overdoses. Symptoms included nausea,
vomiting and ataxia.
Oral metronidazole has been studied as a radiation
sensitizer in the treatment of malignant tumours.
Neurotoxic effects including seizures and peripheral
neuropathy, have been reported after 5 to 7 days of
doses of 6 to 19.4 g every other day.
Nausea and vomiting (Siegel & Weisz, 1984; Lewis &
Kenna, 1967).
9.1.2 Inhalation
Not relevant.
9.1.3 Skin exposure
No data available (vaginal).
9.1.4 Eye contact
Not relevant.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
Nausea, headache, dry mouth, gastrointestinal
disturbances, rash.
Peripheral neuropathy: distal glove-stocking
hypoalgesia, hyperalgesia, paraesthesias of toes,
feet and calves (Bradley et al. 1977; Coxon & Pallis,
1976; Ramsay, 1968).
Central nervous system disturbances: disorientation,
ataxia, dysarthria, paraesthesias, grand mal seizures
(Halloran, 1982; Kusumi et al. 1980; Frytak, et al.
1978).
9.2.2 Inhalation
Not relevant.
9.2.3 Skin exposure
Not relevant.
9.2.4 Eye contact
Not relevant.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
Metronidazole overdoses are rarely fatal and usually do
not lead to prolonged periods of morbidity.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
No data available.
9.4.2 Respiratory
No data available.
9.4.3 Neurological
9.4.3.1 Central nervous system (CNS)
Neurotoxic effects including
seizures have been reported after 5 to 7
days of doses of 6 to 19.4 g every other
day.
9.4.3.2 Peripheral nervous system
Neurotoxic effects including
peripheral neuropathy, have been reported
after 5 to 7 days of doses of 6 to 19.4 g
every other day.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Pseudomembranous colitis has been requently
observed (Saginur et al. 1980; Teasley et al.,
1983).
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Other
No data available.
9.4.7 Endocrine and reproductive systems
Gynaecomastia has been observed after 2 weeks
of therapy.
(Fagan et al., 1985).
9.4.8 Dermatological
No data available.
9.4.9 Eye, ear, nose, throat: local effects
No data available.
9.4.10 Haematological
Leucopenia has been reported.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
No data available.
9.4.12.3 Others
No data available.
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
No data available.
9.5 Other
No data available.
9.6 Summary
No data available.
10. MANAGEMENT
10.1 General principles
There is no specific antidote for metronidazole
poisoning. Therefore management of the patient should consist
of symptomatic and supportive therapy.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
No data available.
10.2.2 Biomedical analysis
Blood counts to monitor leucopenia. Hepatic
function tests are important because in hepatic
disease the metabolism of metronidazole is delayed.
It should, however, be taken into account that
metronidazole may interfere with transaminase
determination, leading to falsely decreased serum
values.
(Rissing et al., 1978)
10.2.3 Toxicological analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic/specific
treatment
Assess airway, breathing and circulation. Provide
symptomatic treatment. Diazepam is indicated for
seizures.
10.4 Decontamination
In the fully conscious patient, consider emesis or
gastric lavage if patient seen within 1 or 2 hours after
ingestion. Activated charcoal should be given afterwards. The
use of a cathartic is no longer recommended.
10.5 Elimination
Haemodialysis may theoretically have some value because
of the moderate volume of distribution and low protein
binding. However, no data is available.
10.6 Antidote treatment
10.6.1 Adults
There is no specific antidote for
metronidazole overdose. Therefore management of the
patient should consist of symptomatic and supportive
therapy.
10.6.2 Children
There is no specific antidote for
metronidazole overdose. Therefore management of the
patient should consist of symptomatic and supportive
therapy.
10.7 Management discussion
Not required.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
No data available.
11.2 Internally extracted data on cases
No data available.
11.3 Internal cases
No data available.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
No data available.
12.2 Specific preventive measures
No data available.
12.3 Other
No data available.
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Authors A. van Dyk
Hospital Pharmacist
Utrecht
Netherlands
Dr A.N.P. van Heijst
Bosch en Duin
Netherlands
Tel: 31-30-287178
Date 16 February 1990
Peer Review Cardiff, United Kingdom, February 1994 (Group
members: Dr R. Fernando, Dr K. Hartigan-Go, Dr G.
Heinemeyer, Dr N. Maramba, Dr E. Wickstrom)