Indications:
Treatment of symptomatic Trichomonas in males and females when presence of Trichomonas has been confirmed by appropriate tests.
Treatment of asymptomatic Trichomonas in females when there is presence of endometrial-associated organisms. Since there is no evidence that presence of the Trichomonas can interfere with accurate assessment of abnormal cytological smears, additional smears should be performed after eradication of the parasites. T. vaginalis infection is a venereal disease. Therefore, asymptomatic sexual partners of treated patients should be treated simultaneously to prevent reinfection.
Treatment of acute intestinal amebiasis (amebic dysentery) and amebic liver abscess. In amoebic liver abscess, metronidazole therapy dose not exclude aspiration or drainage of pus.
Treatment of severe infections caused by susceptible anaerobes and prevention of postsurgical infections. In mixed anaerobic and aerobic infections, appropriate antibiotics for treatment of aerobic infentions should be indicated on combination with Mekacap hard capsules.
- Intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroidesincluding fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus), Clostridium species, Eubacterium species, Peptococcus niger or Peptostreptococcus species.
- Skin and skin structure infections caused by Bacteroidesincluding fragilis group, Clostridium species, Peptococcus niger, or Fusobacterium species.
- Gynecologic infections including endometritis, endomyometritis, ovarian abscess and postsurgical vaginal cuff infection, caused by Bacteroides species including the fragilis group, Clostridium species, Peptococcus niger or Peptostreptococcus species.
- Bacterial septicemia caused by Bacteroides species including the fragilis group, Clostridium species.
- Infections of bone and joint, central nervous system including meningitis, brain abscess, lower respiratory tract infection including pneumonia, empyema, lung abscess and endocarditis caused by Bacteroides species including fragilis group.
To reduce development of drug-resistant bacteria and maintain effectiveness of Mekacap and other anti-bacterial drugs, Mekacap should only be used only to treat or prevent infections identified or suspected of being caused by susceptible bacteria. When culture and susceptibility information is available, selecting or modifying appropriate antibiotic therapy should be considered. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Administration and dosage:
Administration: To be taken with water, no chewing during or after meal.
Dosage:
Elderly: In elderly patients, the pharmacokinetics of metronidazole may be altered. Therefore, serum concentration monitoring may be necessary to adjust metronidazole dosage accordingly.
Trichomoniasis:
In female: 1 capsule, twice daily in 7 days. Pregnant patients should not be treated in the first trimester.
When re-treatment is required, the interval between therapies is 4 – 6 weeks and presence of Trichomonas shoud be reconfirmed by appropriate tests. Total and differential leukocyte counts should be made before and after re-treatments.
In male: Treatment should be individualized as for the female.
Amebiasis:
Adults: Acute amoebic dysentery and amoebic liver abscess: 750 mg, 3 times daily in 5 – 10 days.
Pediatric patients more than 1 year of age: 35 – 50 mg/kg/24 hours, divided into 3 times, in 10 days.
Anaerobic infections: In most severe anaerobic infection treatments, intravenous metronidazole is usually administered initially followed by oral therapy with Mekacap hard capsules as prescribed by physician.
Adults: 7.5 mg/kg every 6 hours. Do not exceed 4 g in 24 hours.
The usual duration of treatment is 7 – 10 days, however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.
In patients with severe liver disease, metronidazole metabolism is slow, with accumulation of metronidazole and its metabolites in plasma.
The dose of metronidazole should not be reduced in anuric patients since accumulated metabolites may be rapidly removed by dialysis.
Some special attention on the handling of the medicine before and after use:
There are no special requirements for handling this medicine afer use.
Contraindications:
Hypersensitivity to nitroimidazole, metronidazole or to any of excipients of this medicine.
In patients with Trichomoniasis, contraindicated during the first trimester of pregnancy.
Warnings and precautions for use:
Regular clinical and laboratory monitoring (especially leukocyte count) is required if Mekacap is indicated for more than 10 days and patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paresthesia, ataxia, vertigo, convulsive disorder).
Metronidazole should be indicated with caution in patients with severe and chronic central and peripheral nervous system disease due to the risk of neurologic symptom exacerbation.
Cases of severe hepatotoxicity/acute liver impairment, including fatals with rapid onset after initation of therapy in patients with Cockayne syndrome have been reported with systemic metronidazole-containing products. Therefore, for such patients, metronidazole should be indicated after careful risk-benefit assessment and only when no alternative treatment is available. Liver function tests should be performed right before initiating, during and after the end of treatment until liver function is within normal range or until baseline values are reached. If liver function tests are significantly increased during treatment, the drug should be discontinued.
Patients with Cockayne syndrome should immediately inform any symptoms of potential liver damage to physician and discontinue metronidazole.
Cases of severe skin reaction such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or acute generalised exanthematous pustulosis (AGEP) syndrome have been reported with metronidazole. If symptoms or signs of SJS, TEN or AGEP occur, treatment must be discontinued immediately.
It is possible that after Trichomonas vaginalis is eliminated, gonococcal infection is still existing.
Half-life of metronidazole is unchanged in presence of renal impairment. Therefore, dose reduction of metronidazole is not necessary. However, such patients retain metabolites of metronidazole. Its clinical significance is currently unknown.
In hemodialysis patients, metronidazole and its metabolites are effectively eliminated during the 8-hour hemodialysis period. Therefore, metronidazole should be reindicated immediately after hemodialysis.
No dose adjustment is required in patients with renal impairment undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Metronidazole is metabolized mainly by oxidation in liver. Significant impairment of metronidazole clearance may occur in cases of progressive liver impairment. Significant accumulation may occur in patients with hepatic encephalopathy, and high plasma concentrations of metronidazole may contribute to symptoms of encephalopathy. Therefore, Mekacap should be indicated with caution to patients with hepatic encephalopathy. Daily dose should be reduced to 1/3 and may be taken once daily.
Patients should be warned that Mekacap darken urine.
Because there is insufficient evidence of mutagenicity in humans, long-term use of the drug should be carefully considered.
Pregnancy and lactation:
There has been no sufficient study of metronidazole safety during pregnancy, but it has been widely used for many years without obvious side effects. However, like other drugs, Mekacap should not be indicated during pregnancy or lactation unless considered necessary by physician; in these cases, short-term treatment, high dose is not recommended.
Effects on ability to drive and operate machinery:
Patients should be warned about possibility of drowsiness, dizziness, confusion, hallucinations, convulsions or transient visual disturbances and advised not to drive or operate machinery if these symptoms occur.
Interaction, incompatibilities of medicine:
Interaction with other medicinal products and other forms of interaction:
Patients should not drink alcohol during metronidazole therapy and for at least 48 hours afterwards because of potential for a disulfiram-type reaction (antabuse effect). Psychotic reactions have been reported in patients taking concomitant metronidazole and disulfiram.
Some ancoagulants effects have been reported when metronidazole is indicated with oral warfarin-type anticoagulant. Dose may be required reduction later. Prothrombin time should be monitored. There is no interaction with heparin.
Evidence of renal damage has been reported in patients treated concomitantly with lithium and metronidazole. Lithium treatment should be tapered or discontinued prior to metronidazole administration. Lithium, creatinine and electrolyte concentrations should be monitored in patients treated with lithium while taking metronidazole.
Concomitant administration of metronidazole and phenobarbital or phenytoin increases the metabolism of metronidazole to much higher rate than normal, elimination half-life being reduced to about 3 hours.
Metronidazole reduces 5-fluorouracil clearance and may therefore increase 5-fluorouracil toxicity.
Patients taking ciclosporin are at risk of increased serum ciclosporin concentration. Close monitoring of ciclosporin and serum creatinine is recommended when co-administered.
Busulfan plasma concentration may be increased by metronidazole, can lead to severe busulfan toxicity.
Incompatibilities:
Because there are no studies of drug incompatibility, do not mix this drug with other drugs.
Undesirable effects:
Side effects are classified according to frequency: Very common (ADR ≥ 1/10), common (1/100 ≤ ADR < 1/10), uncommon (1/1,000 ≤ ADR < 1/100), rare (1/10,000 ≤ ADR < 1/1,000), very rare (ADR < 1/10,000); can not be estimated from the available data “Not known”.
| Organ system | Undesirable effects |
| Blood and lymphatic system disorders | |
| Very rare | Agranulocytosis, neutropenia, thrombocytopenia, leukopenia |
| Not known | Leukopenia |
| Immune system disorders | |
| Rare | Anaphylaxis |
| Not known | Angioedema, urticaria, fever |
| Metabolic and nutritional disorders | |
| Not known | Anorexia |
| Psychiatric disorders | |
| Very rare | Psychiatric disorders, including confusion and hallucinations |
| Not known | Depressed mood |
| Nervous system disorder | |
| Very rare | Encephalopathy (confusing, fever, headache, hallucinations, paralysis, sensitivity to light, visual and movement disorder, stiff neck) and subacute cerebellar syndrome (ataxia, dyskinesia, asthenia, vibration, tremor), drowsiness, dizziness, headache, convulsions |
| Not known | During intensive and/or prolonged metronidazole therapy, peripheral sensory neuropathy or transient epileptic seizures. In most cases, neuropathy disappeared after therapy discontinuation or dosage decrease. Aseptic meningitis |
| Eye disorders | |
| Very rare | Visual disorders (diplopia and transient myopia) |
| Not known | Optic neuropathy/neuritis |
| Ear and labyrinth disorders | |
| Not known | Hearing impairment/hearing loss, tinnitus |
| Gastrointestinal disorders | |
| Not known | Taste disturbance, oral mucositis, tongue discoloration, nausea, vomiting, gastrointestinal disturbances such as epigastric pain and diarrhea |
| Hepatobiliary disorders | |
| Very rare | Elevated liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and hepatocellular injury, jaundice and pancreatitis are reversible upon discontinuation of the drug.
Cases of liver impairment requiring liver transplantation have been reported in patients treated with metronidazole in combination with other antibiotics. |
| Skin and subcutaneous tissue disorders | |
| Very rare | Skin rash, pustular rash, acute generalized pustular syndrome, pruritus, flushing |
| Not known | Erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis, fixed pigmented erythema |
| Musculoskeletal and connective tissue disorders | |
| Very rare | Muscle pain, joint pain |
| Renal and urinary disorders | |
| Very rare | Dark urine |
Inform your doctor or pharmacist of any undesirable effects occured while taking the drug.
Overdose and management:
Overdose: Single doses of metronidazole, up to 12 g, have been reported in suicidality and accidental overdose. Symptoms include vomiting, ataxia, and mild disorientation.
Management: There is no specific antidote. In case of suspected overdose, treatment should be symptomatic and supportive.
Pharmacodynamics:
Pharmacotherapeutic group: Systemic antibiotics and antiparasitic drugs.
ATC code: J01XD01, P01AB01.
Metronidazole is active against protozoa and bacteria, effective against Trichomonas vaginalis and other protozoa including Entamoeba histolytica and Giardia lamblia and against anaerobic bacteria.
Pharmacokinetics:
Metronidazole is rapidly and almost completely absorbed; peak plasma concentration is reached after 20 minutes to 3 hours. Half-life of metronidazole is 8.5 ± 2.9 hours. Metronidazole can be used in chronic renal impairment; it is rapidly eliminated from plasma by hemodialysis. Metronidazole is excreted in milk but in infants lactated by mothers taking normal dose will be significantly less than those lactated by mothers receiving therapeutic infant dose.
Storage conditions, shelf life, quality specification of the medicine:
Storage conditions: Protect from humidity and light, below 30oC.
Shelf life: 36 months from the manufacture date.
Quality specification: In house.
A1203023101
