Metronidazole: Organs and Systems
Generic Name: Metronidazole
Under what local brands and in what dosages is generic Metronidazole sold in pharmacies of Britain, United States, and Canada?
In pharmacies of the United States, Great Britain and Canada the pharmacists offer you to buy Metronidazole according to your prescription or without a prescription under such brand names and in such strengths and dosage forms:
| UK | US | Canada |
| Flagyl 200mg Tablets Flagyl 400mg Tablets Flagyl 500mg/100ml Solution Flagyl S Suspension Metrogel Metrolyl 1g Suppositories Metronidazole 200mg Tablets Metronidazole 400mg Tablets Metronidazole Tablets 500mg Norzol 200mg/5ml Oral Suspension Rozex Cream Rozex Gel Zidoval 7.5 mg/g Vaginal Gel Zyomet Gel | Flagyl 250mg Tablets Flagyl 375mg Capsules Flagyl 500mg Tablets Flagyl ER 750mg Tablets Flagyl I.V. 500mg Injectable Metrocream 0.75% Cream Metrogel 0.75% & 1% Gel Metronidazole 375mg Capsules Metronidazole 0.75% Cream Metronidazole 0.75% & 1% Gel Metronidazole 250mg Tablets Metronidazole 500mg Tablets Metronidazole 750mg Tablets Metronidazole 500mg/100ml Injectable | Flagyl 500mg Tablets Flagyl Cream 10% Flagystatin Vaginal OvulE 500mg Metrocream 0.75% Cream Metrogel 0.75% & 1% Gel Metronidazole 250mg Tablets Metronidazole 500mg Tablets Metronidazole 5mg/ml Injectable PMS-Metronidazole 250mg Tablets PMS-Metronidazole 500mg Tablets |
Cardiovascular
Thrombophlebitis can occur after intravenous administration of metronidazole; an incidence of 6% has been cited.
Respiratory
Pneumonitis has been attributed to metronidazole, with recurrence after rechallenge.
Nervous system
Central nervous system symptoms can occur with standard doses of metronidazole, but they are mainly seen with high doses and especially when such doses are given for a long time. Under the latter conditions, there was a 25% incidence of such symptoms as headaches, dizziness, tremor, ataxia, and confusion. A polyneuropathy is a well-recognized adverse effect of metronidazole. A 6% incidence of neuropathy has been quoted; polyneuropathy, mainly sensory in nature, has been recorded during the treatment of Crohn’s disease, but again in connection with the prolonged use of high doses.
This complication is not restricted to patients with Crohn’s disease; it is also seen when metronidazole is given for other purposes, such as radiosensitization. Electrophysiological studies have suggested distal sensory axonal degeneration, with loss of sensory nerve potential over the distal segment and normal motor nerve conduction. In some cases the severity of clinical and electrophysiological abnormalities is closely related to the total amount of metronidazole administered. Metronidazole is structurally similar to thiamine, and thiamine-synthesizing gut flora may synthesize a neurotoxic analogue of thiamine from ingested metronidazole. However, this hypothesis is weakened by the fact that nitroheterocyclic drugs other than metronidazole are also neurotoxic, despite a much weaker structural analogy to thiamine. Peripheral neuropathy was associated in one case with intermittent use of metronidazole (2 g/day for 5 days every other month).
A 65-year-old white woman with small intestine bacterial overgrowth developed persistent numbness and tingling of her upper and lower extremities. She had been taking alternating courses of tetracycline and metronidazole for 5 days every other month for about 1 year. Other medications included amitriptyline, lisinopril, digoxin, omeprazole, and tamoxifen. Serum vitamin Bi2 and folate concentrations were within the reference ranges. She had reduced sensation in a stocking-glove distribution, reduced sensation to touch and pin-prick, intact reflexes, and no weakness. Neuropathy was attributed to metronidazole, which was withdrawn.
After 4 months she reported improvement. On follow-up at 5 months, there was no evidence of peripheral neuropathy. Metronidazole-associated sensory neuropathy usually presents with pain and reduced thermal and pin-prick sensation, but normal strength, proprioception, and tendon reflexes. Four patients with metronidazole-associated sensory symptoms had detailed electrodiagnostic studies and nerve or muscle biopsies. All had taken different doses of metronidazole and one (with a mitochondrial myopathy) had only used the drug topically. After withdrawal, sensory complaints persisted without progression in two patients and resolved in one. In the fourth, a lower dosage led to partial resolution.
Nerve conduction studies were normal in all four cases, but quantitative sensory testing and quantitative sudomotor autonomic reflex testing showed abnormalities of small-fiber function. A sural nerve biopsy from one patient confirmed some loss of small myelinated axons.
Metronidazole probably caused a small-fiber neuropathy in these four cases. The authors also reviewed nerve conduction studies in 30 reported cases of metronidazole-associated neuropathy; they were sometimes normal, suggesting that sensory symptoms related to metronidazole may be caused by a mixture of small-fiber and large-fiber sensory dysfunction.
Aseptic meningitis is a rare, possibly allergic adverse effect of metronidazole; the one published case was well documented, with positive rechallenge. There has been a report of visual loss and headache after metronidazole.
A 68-year-old man with a tooth abscess had a tooth extraction and received amoxicillin. A few weeks later he developed toothache again and was given amoxicillin and metronidazole 400 mg tds; he took no other drugs. Six hours after the first dose he developed a headache. He continued with metronidazole for a total of three doses, and 6 hours after the last dose the headache resolved. Two days later he noticed flashing lights in both eyes. He then developed a central visual field defect and progressive visual loss. His blood pressure was 220/120 mmHg, but it settled spontaneously.
Visual acuity was 6/12 in both eyes and fundoscopy showed marked disc swelling with hemorrhages, without other features of hypertensive retinopathy. Full blood count, plasma viscosity, routine biochemistry, vasculitis screen, anticardiolipin antibodies, angiotensin converting enzyme assay, chest X-ray, CT of the brain and orbits, MRI, and MRA were all normal. CSF examination showed an opening pressure of 24 cm of water and 13 white cells/|j,l.
Over the next few months his visual symptoms slowly improved but he developed secondary optic atrophy. In this case there was no other obvious cause for visual loss and it could have been caused by metronidazole. The exact mechanism was unclear, but it may have been related to raised intracranial pressure. Convulsions occurred in an 87-year-old man who had taken metronidazole. Encephalopathy associated with metronidazole has been reported in a patient with chronic renal insufficiency.
A 58-year-old woman with end-stage renal insufficiency secondary to diabetic nephropathy developed abdominal wall cellulitis 4 days after insertion of a peritoneal dialysis catheter. She was given vancomycin, cefepime, and metronidazole in reduced doses (doses not stated) and 2 days later developed dysarthria, an intention tremor, dysmetria, and dysdiadochokinesia. “Routine” biochemical tests were unchanged and a CT scan of the brain was unremarkable, but an MRI scan showed cerebral and cerebellar atrophy with multifocal ischemic glial lesions. Metronidazole was withdrawn and 2 days later her symptoms and signs had completely resolved. It is difficult to ascribe encephalopathy unequivocally to metronidazole in this case.
Sensory systems
Eyes
Acute myopia occurred after 11 days of treatment with metronidazole for Trichomonas infection; it resolved within 4 days after withdrawal but recurred on rechal-lenge. The combined figures of two major American reporting systems for adverse reactions listed seven cases of retrobulbar or optic neuritis associated with oral metronidazole; two had a concurrent peripheral neuropathy. However, there is insufficient information to evaluate these reports.
Ears
Two reports of moderate to severe sensorineural deafness after metronidazole therapy, which resolved slowly after therapy ended suggest that this is an additional adverse effect. Both cases of deafness were preceded by tinnitus, which may be a warning to withdraw the drug.
Hematologic
Metronidazole can produce leukopenia and neutropenia, usually only associated with prolonged therapy and reversible on withdrawal. One case each of agranulocytosis and of aplastic anemia have been reported and a single case of hemolytic-uremic syndrome in six children.
Gastrointestinal
Anorexia, nausea, vomiting, abdominal pain, and diarrhea have all been reported in patients taking metronidazole. The use of a large single dose most commonly leads to these complaints. A metallic taste also seems to be quite common, as is the occurrence of a black tongue. Although metronidazole is often used to treat pseudo-membranous colitis, it can also occasionally cause it.
Liver
Raised serum liver enzyme activities were reported in one case about 15 years ago, but there has been no more recent confirmation.
Pancreas
Pancreatitis has been reported in various individual case histories, but there is reason to think that some of these cases at least were due to other factors, such as alcohol use. • Pancreatitis has been described in a 63-year-old woman with Crohn’s disease, coinciding with the administration of metronidazole and disappearing 1-2 days after withdrawal, but even here there was little support for a causal link. • Pancreatitis was attributed to metronidazole in a 61-year-old woman given intravenous metronidazole 500 mg 6-hourly. The relation between pancreatitis and metronidazole in this case was less convincing than in previously reported cases, as there was no rechal-lenge.
Urinary tract
Darkening of the urine can occur in patients taking metronidazole; this is a harmless discoloration, mostly seen during prolonged treatment.
Skin
Pruritus and rashes have been reported in patients taking metronidazole, including a fixed drug eruption and a pityriasis rosea-like eruption. Urticaria after a single dose has been reported but could have been coincidental In a case of fixed drug eruption, a provocation test showed cross-reactivity with tinidazole but not with secnidazole.
Reproductive system
A genital mucosal erosion occurred in a 38-year-old woman who had taken metronidazole 400 mg tds for 10 days for bacterial vaginitis.