Single oral doses of Nidazol, up to 12g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for Nidazol overdosage. In cases of suspected massive overdose, symptomatic and supportive treatment should be instituted.
Single oral doses of metronidazole, up to 12g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for metronidazole overdosage. In cases of suspected massive overdose, symptomatic and supportive treatment should be instituted.
There is no human experience with overdosage of metronidazole vaginal gel. Vaginally applied metronidazole gel, 0.75% could be absorbed in sufficient amounts to produce systemic effects.
There is no human experience with overdosage of metronidazole vaginal gel. Vaginally applied Nidazol could be absorbed in sufficient amounts to produce systemic effects.
Not applicable.
Not applicable
The frequency of adverse events listed below is defined using the following convention:
Very common (>1/10); common (>1/100 to < 1/10); uncommon (>1/1,000 to < 1/100); rare (>1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).
Serious adverse reactions occur rarely with standard recommended regimens. Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended, are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy.
Blood and lymphatic system disorders:
Very rare: agranulocytosis, neutropenia, thrombocytopenia, and pancytopenia
Not known: leucopenia.
Immune system disorders:
Rare: anaphylaxis,
Not known: angioedema, urticaria, fever.
Metabolism and nutrition disorders:
Not known: anorexia.
Psychiatric disorders:
Very rare: Psychotic disorders, including Confusion and hallucinations.
Not known: depressed mood
Nervous system disorders:
Very rare:
- Encephalopathy (eg. confusion, fever, headache, hallucinations, paralysis, light sensitivity, disturbances in sight and movement, stiff neck) and subacute cerebellar syndrome (eg. ataxia, dysathria, gait impairment, nystagmus and tremor) which may resolve on discontinuation of the drug.
- Drowsiness, dizziness, convulsions, headaches
Not known:
- during intensive and/or prolonged Nidazol therapy, peripheral sensory neuropathy or transient epileptiform seizures have been reported. In most cases neuropathy disappeared after treatment was stopped or when dosage was reduced.
- Aseptic meningitis
Eye disorders:
Very rare: vision disorders such as diplopia and myopia, which, in most cases, is transient.
Not known: optic neuropathy/neuritis
Ear and labyrinth disorders:
Not known: hearing impaired/hearing loss (including sensorineural), tinnitus
Gastrointestinal disorders:
Not known: Taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal disturbances such as epigastric pain and diarrhoea.
Hepatobiliary disorders:
Very rare:
- increase in liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and hepatocellular liver injury, jaundice and pancreatitis which is reversible on drug withdrawal.
- Cases of Liver failure requiring liver transplant have been reported in patients treated with Nidazol in combination with other antibiotic drugs
Skin and subcutaneous tissue disorders:
Very rare: skin rashes, pustular eruptions, pruritis, flushing
Not known: erythema multiforme, Steven-Johnson syndrome or toxic epidermal necrolysis, fixed drug eruption.
Musculoskeletal, connective tissue and bone disorders:
Very rare: myalgia, arthralgia.
Renal and urinary disorders:
Very rare: darkening of urine (due to Nidazol metabolite).
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.
The frequency of adverse events listed below is defined using the following convention:
very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).
Serious adverse reactions occur rarely with standard recommended regimens. Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended, are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy.
Blood and lymphatic system disorders:
Very rare: agranulocytosis, neutropenia, thrombocytopenia, pancytopenia
Not known: leucopenia.
Immune system disorders:
Rare: anaphylaxis
Not known: angiodema, urticaria , fever.
Metabolism and nutrition disorders:
Not known: anorexia.
Psychiatric disorders:
Very rare: psychotic disorders, including confusion and hallucinations.
Not known: depressed mood
Nervous system disorders:
Very rare:
- encephalopathy (eg. confusion, fever, headache, hallucinations, paralysis, light sensitivity, disturbances in sight and movement, stiff neck) and subacute cerebellar syndrome (eg. ataxia, dysathria, gait impairment, nystagmus and tremor) which may resolve on discontinuation of the drug.
- drowsiness, dizziness, convulsions, headaches
Not known:
- during intensive and/or prolonged metronidazole therapy, peripheral sensory neuropathy or transient epileptiform seizures have been reported. In most cases neuropathy disappeared after treatment was stopped or when dosage was reduced.
- aseptic meningitis
Eye disorders:
Very rare: vision disorders such as diplopia and myopia, which, in most cases, is transient.
Not Known: optic neuropathy/neuritis
Ear and labyrinth disorders
Not known: hearing impaired/hearing loss (including sensorineural), tinnitus
Gastrointestinal disorders:
Not known: taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal disturbances such as epigastric pain and diarrhoea.
Hepatobiliary disorders:
Very rare:
- increase in liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and hepatocellular liver injury, jaundice and pancreatitis which is reversible on drug withdrawal.
- cases of liver failure requiring liver transplant have been reported in patients treated with metronidazole in combination with other antibiotic drugs.
Skin and subcutaneous tissue disorders:
Very rare: skin rashes, pustular eruptions, pruritis, flushing
Not known: erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis, fixed drug eruption
Musculoskeletal, connective tissue and bone disorders:
Very rare: myalgia, arthralgia.
Renal and urinary disorders:
Very rare: darkening of urine (due to metronidazole metabolite).
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.
Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to VANDAZOLE compared to another formulation of vaginal metronidazole in 220 women in a single trial. The population was non-pregnant females (age range 18 to 72 years, the mean was 33 years +/- 11 years) with bacterial vaginosis. The racial demographic of those enrolled was 71 (32%) of White, 143 (65%) of Black, 3 (1%) of Hispanic, 2 (1%) of Asian, and 1 (0%) of other. Patients administered an applicator full of VANDAZOLE (metronidazole vaginal gel) intravaginally once daily at bedtime for 5 days.
There were no deaths or serious adverse reactions related to drug therapy in the clinical trial. VANDAZOLE (metronidazole vaginal gel) was discontinued in 5 patients (2.3%) due to adverse reactions.
The incidence of all adverse reactions in VANDAZOLE (metronidazole vaginal gel) -treated patients was 42% (92/220). Adverse reactions occurring in ≥ 1% of patients were: fungal infection* (12%), headache (7%), pruritus (6%), abdominal pain (5%), nausea (3%), dysmenorrhea (3%), pharyngitis (2%), rash (1%), infection (1%), diarrhea (1%), breast pain (1%), and metrorrhagia (1%).
* Known or previously unrecognized vaginal candidiasis may present more prominent symptoms during therapy with VANDAZOLE (metronidazole vaginal gel). Approximately 10% of patients treated with VANDAZOLE (metronidazole vaginal gel) developed Candida vaginitis during or immediately after therapy.
Additional uncommon events, reported by < 1% of those women treated with VANDAZOLE (metronidazole vaginal gel) included:
General: allergic reaction, back pain, flu syndrome, mucous membrane disorder, pain
Gastrointestinal: anorexia, constipation, dyspepsia, flatulence, gingivitis, vomiting
Nervous System: depression, dizziness, insomnia
Respiratory System: asthma, rhinitis
Skin and Appendages: acne, sweating, urticaria
Urogenital System: breast enlargement, dysuria, female lactation, labial edema, leucorrhea, menorrhagia, pyleonephritis, salpingitis, urinary frequency, urinary tract infection, vaginitis, vulvovaginal disorder
Other Metronidazole Formulations Other Vaginal FormulationsOther reactions that have been reported in association with the use of other formulations of metronidazole vaginal gel include: unusual taste and decreased appetite.
Topical (Dermal) FormulationsOther reactions that have been reported in association with the use of topical (dermal) formulations of metronidazole include skin irritation, transient skin erythema, and mild skin dryness and burning. None of these adverse reactions exceeded an incidence of 2% of patients.
Oral and Parenteral FormulationsThe following adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of metronidazole:
Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings.
Nervous System: The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. In addition, patients have reported syncope, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia.
Gastrointestinal: Abdominal discomfort, nausea, vomiting, diarrhea, an unpleasant metallic taste, anorexia, epigastric distress, abdominal cramping, constipation, “furry” tongue, glossitis, stomatitis, pancreatitis, and modification of taste of alcoholic beverages.
Genitourinary: Overgrowth of Candida in the vagina, dyspareunia, decreased libido, proctitis.
Hematopoietic: Reversible neutropenia, reversible thrombocytopenia.
Hypersensitivity Reactions: Urticaria; erythematous rash; Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing; nasal congestion; dryness of the mouth, vagina, or vulva; fever; pruritus; fleeting joint pains.
Renal: Dysuria, cystitis, polyuria, incontinence, a sense of pelvic pressure, darkened urine.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience Clinical Trial Experience In Adult SubjectsThe safety of Nidazol was evaluated in a randomized, double-blind, vehicle-controlled study in subjects with bacterial vaginosis. A total of 321 non-pregnant females with a mean age of 33.4 years (range 18 to 67 years) received Nidazol. Subjects were primarily Black/African American (58.3%) or White (39.3%). Subjects administered a single dose of Nidazol at bedtime on the first day of the study.
There were no deaths or serious adverse reactions in this trial. Adverse reactions were reported by 19.0% of subjects treated with Nidazol versus 16.1% of subjects treated with Vehicle Gel.
Adverse reactions occurring in ≥1% of subjects receiving Nidazol were: vulvovaginal candidiasis (5.6%), headache (2.2%), vulvovaginal pruritus (1.6%), nausea (1.6%), diarrhea (1.2%), and dysmenorrhea (1.2%). No subjects discontinued treatment due to adverse reactions.
Clinical Trial Experience In Pediatric SubjectsThe safety of Nidazol was evaluated in a multicenter, open-label study evaluating the safety and tolerability of Nidazol in 60 pediatric subjects between the ages of 12 and less than 18 years old all of whom were treated with a single dose of Nidazol administered once at bedtime intravaginally. Most subjects in this study were either Black/African-American, non-Hispanic (47%) or Hispanic (35%)
Safety in pediatric female subjects aged 12 to less than 18 years old was comparable to adult women. No deaths occurred and no subjects discontinued treatment due to adverse reactions. Adverse reactions occurring in ≥ 1% of pediatric subjects included: vulvovaginal discomfort (2%).
Other Metronidazole Formulations Other Vaginal FormulationsOther reactions that have been reported in association with the use of other formulations of metronidazole vaginal gel include: unusual taste and decreased appetite.
Topical (Dermal) FormulationsOther reactions that have been reported in association with the use of topical (dermal) formulations of metronidazole include skin irritation, transient skin erythema, and mild skin dryness and burning. None of these adverse reactions exceeded an incidence of 2% of patients.
Oral And Parenteral FormulationsThe following adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of metronidazole:
CardiovascularFlattening of the T-wave may be seen in electrocardiographic tracings.
Nervous SystemThe most serious adverse reactions reported in patients treated with oral metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. In addition, patients have reported syncope, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia.
GastrointestinalAbdominal discomfort, nausea, vomiting, diarrhea, an unpleasant metallic taste, anorexia, epigastric distress, abdominal cramping, constipation, “furry” tongue, glossitis, stomatitis, pancreatitis, and modification of taste of alcoholic beverages.
GenitourinaryOvergrowth of Candida in the vagina, dyspareunia, decreased libido, proctitis.
HematopoieticReversible neutropenia, reversible thrombocytopenia.
Hypersensitivity ReactionsUrticaria; erythematous rash; Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing; nasal congestion; dryness of the mouth, vagina, or vulva; fever; pruritus; fleeting joint pains.
RenalDysuria, cystitis, polyuria, incontinence, a sense of pelvic pressure, darkened urine.
Nidazol has been shown to be carcinogenic in the mouse and in the rat following chronic oral administration however similar studies in the hamster have given negative results. Epidemiological studies have provided no clear evidence of an increased carcinogenic risk in humans.
Nidazol has been shown to be mutagenic in bacteria in vitro. In studies conducted in mammalian cells in vitro as well as in rodent or humans in vivo, there was inadequate evidence of a mutagenic effect of Nidazol, with some studies reporting mutagenic effects, while other studies were negative.
Metronidazole has been shown to be carcinogenic in the mouse and in the rat following chronic oral administration however similar studies in the hamster have given negative results. Epidemiological studies have provided no clear evidence of an increased carcinogenic risk in humans.
Metronidazole has been shown to be mutagenic in bacteria in vitro. In studies conducted in mammalian cells in vitro as well as in rodent or humans in vivo, there was inadequate evidence of a mutagenic effect of metronidazole, with some studies reporting mutagenic effects, while other studies were negative.
Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01X D01
Nidazol is active against a wide range of pathogenic micro-organisms notably species of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella vaginalis. It is also active against Trichomonas, Entamoeba histolytica, Giardia lamblia and Balantidium coli.
Pharmacotherapeutic code: Antibacterials for systemic use, ATC code: J01X D01.
Metronidazole has antiprotozoal and antibacterial actions and is effective against Trichomonas vaginalis and other protozoa including Entamoeba histolytica and Giardia lamblia and against anaerobic bacteria.
Nidazol is rapidly and almost completely absorbed on administration of Nidazol tablets; peak plasma concentrations occur after 20 min to 3 hours.
The half-life of Nidazol is 8.5 ± 2.9 hours. Nidazol can be used in chronic renal failure; it is rapidly removed from the plasma by dialysis. Nidazol is excreted in milk but the intake of a suckling infant of a mother receiving normal dosage would be considerably less than the therapeutic dosage for infants.
Metronidazole is readily absorbed from the rectal mucosa and widely distributed in body tissues. Maximum concentrations occur in the serum after about 1 hour and traces are detected after 24 hours.
At least half the dose is excreted in the urine as metronidazole and its metabolites, including an acid oxidation product, a hydroxy derivative and glucoronide. Metronidazole diffuses across the placenta, and is found in breast milk of nursing mothers in concentrations equivalent to those in serum.
Following a single, intravaginal 5 g dose of Nidazol (equivalent to 65 mg of metronidazole) to 20 healthy female subjects, a mean maximum serum metronidazole concentration (Cmax) of 239 ng/mL was observed (range: 114 to 428 ng/mL). The average time to achieve this Cmax was 7.3 hours (range: 4 to 18 hours). This Cmax is approximately 2% of the mean maximum serum concentration reported in healthy subjects administered a single, oral 500 mg dose of metronidazole tablets (mean Cmax = 12,785 ng/mL).
The extent of exposure [area under the curve (AUC)] of metronidazole, when administered as a single intravaginal 5 g dose of Nidazol (equivalent to 65 mg of metronidazole), was 5,434 ng•hr/mL (range: 1382 to 12744 ng•hr/mL). This AUC0-∞ is approximately 4% of the reported AUC of metronidazole following a single oral 500 mg dose of metronidazole (approximately 125,000 ng•hr/mL).
Patients should be warned about the potential for drowsiness, dizziness, confusion, hallucinations, convulsions or transient visual disorders, and advised not to drive or operate machinery if these symptoms occur.
Patients should be warned about the potential for drowsiness, dizziness, confusion, hallucinations, convulsions or transient visual disorders, and advised not to drive or operate machinery if these symptoms occur.
No special requirements.
No special requirements
