Single oral doses of Розамет, 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 Розамет overdosage. In cases of suspected massive overdose, symptomatic and supportive treatment should be instituted.
Known hypersensitivity to nitroimidazoles, Розамет or any of the excipients.
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 Розамет 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 Розамет 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 Розамет 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.
Розамет 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.
Розамет 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 Розамет, with some studies reporting mutagenic effects, while other studies were negative.
Розамет is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected to be the cause.
Розамет 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.
Розамет is indicated in adults and children for the following indications:
1. The prevention of post-operative infections due to anaerobic bacteria, particularly species of Bacteroides and anaerobic streptococci.
2. The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, and post-operative wound infections from which pathogenic anaerobes have been isolated.
3. Urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male.
4. Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginosis or Gardnerella vaginitis).
5. All forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers).
6. Giardiasis.
7. Acute ulcerative gingivitis.
8. Anaerobically-infected leg ulcers and pressure sores.
9. Acute dental infections (e.g. acute pericoronitis and acute apical infections).
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01X D01
Розамет 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.
Розамет is rapidly and almost completely absorbed on administration of Розамет tablets; peak plasma concentrations occur after 20 min to 3 hours.
The half-life of Розамет is 8.5 ± 2.9 hours. Розамет can be used in chronic renal failure; it is rapidly removed from the plasma by dialysis. Розамет 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.
Regular clinical and laboratory monitoring (especially leukocyte count) are advised if administration of Розамет for more than 10 days is considered to be necessary and patients should be monitored for adverse reactions, such as peripheral or central neuropathy (such as paraesthesia, ataxia, dizziness, convulsive seizures).
Розамет should be used with caution in patients with active or chronic severe peripheral and central nervous system disease due to the risk of neurological aggravation.
The elimination half-life of Розамет remains unchanged in the presence of renal failure. The dosage of Розамет therefore needs no reduction. Such patients however retain the metabolites of Розамет. The clinical significance of this is not known at present.
In patients undergoing haemodialysis, Розамет and metabolites are efficiently removed during an eight hour period of dialysis. Розамет should therefore be re-administered immediately after haemodialysis.
No routine adjustment in the dosage of Розамет need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Розамет is mainly metabolised by hepatic oxidation. Substantial impairment of Розамет clearance may occur in the presence of advanced hepatic insufficiency.
Significant cummulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of Розамет may contribute to the symptoms of the encephalopathy. Розамет should therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily.
Patients should be warned that Розамет may darken urine.
Due to inadequate evidence on the mutagenicity risk in humans , the use of Розамет for longer treatment than usually required should be carefully considered.
Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with cockayne syndrome have been reported with products containing Розамет for systemic use. In this population, Розамет should therefore be used after careful benefit-risk assessment and only if no alternative treatment is available. Liver function tests must be performed just prior to the start of therapy, throughout and after end of treatment until liver function is within normal ranges, or until the baseline values are reached. If the liver function tests become markedly elevated during treatment, the drug should be discontinued.
Patients with Cockayne syndrome should be advised to immediately report any symptoms of potential liver injury to their physician and stop taking Розамет.
There is a possibility that after Trichomonas vaginalis has been eliminated a gonococcal infection might persist.
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.
For oral administration.
Розамет tablets should be swallowed, without chewing, with half a glassful of water during or after meals.
Prophylaxis against anaerobic infection:
Chiefly in the context of abdominal (especially colorectal) and gynaecological surgery.
Adults: 400 mg 8 hourly during 24 hours immediately preceding operation followed by postoperative intravenous or rectal administration until the patient is able to take tablets.
Children < 12 years: 20-30mg/kg as a single dose given 1-2 hours before surgery
Newborns with a gestation age < 40 weeks: 10mg/kg body weight as a single dose before operation
Anaerobic infections:
The duration of a course of Розамет treatment is about 7 days but it will depend upon the seriousness of the patient's condition as assessed clinically and bacteriologically.
Treatment of established anaerobic infection:
Adults: 800 mg followed by 400 mg 8 hourly.
Children > 8 weeks to 12 years of age: The usual daily dose is 20-30 mg/kg/day as a single dose or divided into 7.5 mg/kg every 8 hours. The daily dose may be increased to 40 mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days.
Children < 8 weeks of age: 15 mg/kg as a single dose daily or divided into 7.5 mg/kg every 12 hours.
In newborns with a gestation age <40 weeks, accumulation of Розамет can occur during the first week of life, therefore the concentrations of Розамет in serum should preferable be monitored after a few days therapy.
Prophylaxis against postoperative infections caused by anaerobic bacteria: Children < 12 years: 20-30 mg/kg as a single dose given 1-2 hours before surgery Newborns with a gestation age <40 weeks: 10 mg/kg body weight as a single dose before operation
Protozoal and other infections:
Urogenital trichomoniasis:
Where re-infection is likely, in adults the consort should receive a similar course of treatment concurrently
Adults and adolescents: 2000 mg as a single dose or 200 mg 3 times daily for 7 days or 400 mg twice daily for 5-7 days
Children 1-10 years: 40 mg/kg orally as a single dose or 15 - 30 mg/kg/day divided in 2-3 doses for 7 days; not to exceed 2000 mg/dose
Bacterial vaginosis:
Adults and children over 10 years: 400mg twice daily for 5-7 days or 2000mg as a single dose for 1 day
Amoebiasis:
a) Invasive intestinal disease in susceptible subject:
Adults, elderly and children over 10 years: 800mg three times daily for 5 days.
Children (7-10 years): 400 mg three times daily for 5 days.
Children (3-7 years): 200 mg four times daily for 5 days.
Children (1-3 years): 200 mg three times daily for 5 days.
b) Intestinal disease in less susceptible subjects and chronic amoebic hepatitis:
Adults, elderly and children over 10 years: 400mg three times daily for 5-10 days.
Children (7-10 years): 200 mg three times daily for 5-10 days.
Children (3-7 years): 100 mg four times daily for 5-10 days.
Children (1-3 years): 100 mg three times daily for 5-10 days.
c) Amoebic liver abscess, also forms of extra-intestinal amoebiasis:
Adults, elderly and children over 10 years: 400mg three times daily for 5 days.
Children (7-10 years): 200 mg three times daily for 5 days.
Children (3-7 years): 100 mg four times daily for 5 days.
Children (1-3 years): 100 mg three times daily for 5 days.
d) Symptomless cyst passers:
Adults, elderly and children over 10 years: 400-800mg three times daily for 5-10 days.
Children (7-10 years): 200-400 mg three times daily for 5-10 days.
Children (3-7 years): 100-200 mg four times daily for 5-10 days.
Children (1-3 years): 100-200 mg three times daily for 5-10 days.
Alternatively, 35 to 50 mg/kg daily in 3 divided doses for 5 to 10 days, not to exceed 2400 mg/day
Giardiasis:
Adults, elderly and children over > 10 years: 2000 mg once daily for 3 days, or 400 mg three times daily for 5 days, or 500 mg twice daily for 7 to 10 days
Children 7 to 10 years: 1000 mg once daily for 3 days
Children 3 to 7 years: 600 to 800 mg once daily for 3 days
Children 1 to 3 years: 500 mg once daily for 3 days
Alternatively, as expressed in mg per kg of body weight:
15-40 mg/kg/day divided in 2-3 doses.
Eradication of Helicobacter pylori in paediatric patients:
As a part of a combination therapy, 20 mg/kg/day not to exceed 500 mg twice daily for 7-14 days. Official guidelines should be consulted before initiating therapy
Acute ulcerative gingivitis:
Adults, elderly and children over 10 years: 200 mg three times daily for 3 days.
Children (7-10 years): 100 mg three times daily for 3 days.
Children (3-7 years): 100 mg twice daily for 3 days.
Children (1-3 years): 50 mg three times daily for 3 days.
Acute dental infections:
Adults, elderly and children over 10 years: 200 mg three times daily for 3-7 days.
Leg ulcers and pressure sores:
Adults, elderly and children over 10 years: 400 mg three times daily for 7 days
Children and infants weighing less than 10 kg should receive proportionally smaller dosages.
Elderly: Розамет is well tolerated by the elderly but a pharmacokinetic study suggests cautious use of high dosage regimens in this age group.
No special requirements.
