Qualitative and quantitative composition, Pharmaceutical form, Clinical particulars: therapeutic indications, posology and method of administration, contraindications, special warnings and special precautions for use, Interactions, Pregnancy and lactation effects, Effects on ability to drive and use machines, Undesirable effects, Overdose, Pharmacological properties: pharmacodynamic properties, pharmacokinetics properties, Pharmaceutical particulars: list of excipients, Special precaution for storage, Nature and contents of container and Manufacturer of Chimox Tablet Medicine for Gastrointestinal Worms.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 500 mebendazole.
CHIMOX 500 mg tablet: white to faintly cream-coloured, circular, flat, bevel-edged tablet.
CHIMOX 500mg is indicated for the mass treatment of single or mixed gastrointestinal infestations by Enterobius vermicularis (pinworm); Thichuris trichiur (whipworm); Ascaris lumbricoides (large roundworm); Ancylostoma duodenale, Necator americanus (hookworm) Inpatients living in heavily endemic areas, regular treatment with CHIMOX 500mg, 3-4 times a year will substantially reduce the overall worm load and keep it well below the level of clinical significance.
Posology and Method of Administration
Adults and children above 2 years
1 single tablet of CHIMOX 500mg.
No special procedures, such as diet or use of laxatives are required.
CHIMOX 500 mg tablets should not be used in children below the age of 1 year. In addition, CHIMOX 500mg is contraindicated in persons with a known hypersensitivity to the drug or its components.
Special Warnings and Special Precautions for Use
Use in infants below 2 years of age; as well documented experience in children below 2 years of age is scarce and there have been very exceptional reports of convulsions in this age group, CHIMOX 500mg should not be used and CHIMOX 100mg should only be given to very young children if their worm infestation interferes significantly with the nutritional status and the physical development.
Although a single dose treatment is recommended, there have been rare reports of reversible liver function disturbances, hepatitis and neutropenia described in patients who were treated for hydatid disease with dosages substantially shove those recommended for prolonged periods of time.
Therefore, hematologic parameters and liver function tests should be monitored in patients receiving CHIMOX 500mg for prolonged periods of time.
Results from a case-controlled study investigating an outbreak of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) suggested a possible relationship between SJS/TEN and the concomitant use of mebendazole and metronidazole. Further data suggesting such a drug-drug interaction are not available. Therefore, concomitant use of mebendazole and metronidazole should be avoided.
Interaction with Other Medicinal Products and Other Forms of Interaction
Concomitant treatment with cimetidine may inhibit the metabolism of mebendazole in the liver, resulting in increased plasma concentrations of the drug especially during prolonged treatment. In the latter case, determination of plasma concentrations are recommended in other to allow dose adjustments. Concomitant use of mebendazole and metronidazole should be avoided (see Special warnings and special precautions for use)
Pregnancy and Lactation
Mebendazole has shown embryotoxic and teratogenic activity in rats and in mice at single oral doses. No harmful effects on reproduction were noted in other animal species tested. (See Pre-clinical Safety Data).
The possible risks associated with prescribing CHIMOX 500 mg during pregnancy, particularly during the first trimester, should be weighed against the expected therapeutic benefits.
Mebendazole is only absorbed to a small extent. It is not known whether mebendazole is excreted in human breast milk. Therefore, caution should be exercised when CHIMOX 500mg is administered to nursing women.
Effects on Ability to Drive and Use Machines
CHIMOX does not affect the mental alertness or driving ability.
At the recommended dose, CHIMOX is generally well tolerated However, patients with high parasitic burdens when treated with CHIMOX have manifested diarrhea and abdominal pain.
Within each system organ class, the adverse drug reactions are ranked under the headings of reporting frequency using the following convention;
Very common (> 1/10)
Common (> l/l00, < 1/10)
Uncommon (> l/l000, < 1/100)
Rare (>1/10000, <1/1000)
Very rare (< l/l0000) including isolated reports.
Blood and the lymphatic system disorders
Very rare: neutropenia (with prolonged use at dosages substantially above those recommended)
Immune system disorders
Very rare: hypersennitivity reactions such as anaphylactic and anaphylactoid reactions
Nervous system disorders
Very rare: convulsions in infants (see also Special Warnings and Special Precautions for Use)
Very rare: abdominal pain, diarrhea (these symptoms can also be the result of the worm infestation itself)
Very rare: hepatitis and abnormal liver function tests (with prolonged use at dosages substantially above those recommended)
Skin and subcutaneous tissue disorders
Very rare: toxic epidermal necrolysis, Stevens-Johnson Syndrome, exanthema, angioedema, urticaria, rash.
Renal and urinary disorders
Very rare: glomerulonephritis (with prolonged use at dosages substantially above recommended)
In the event of accidental overdose, abdominal cramps, nausea, vomiting and diarrhea may occur.
There is no specific antidote. Within the first hour after ingestion, gastric lavage may be performed. Activated charcoal may be given if considered appropriate.
Mebendazole interferes with the cellular tubulin formation in the intestines of worms by specifically binding to tubulin and causing ultrastructural degenerative changes in the intestine. As a result, the glucose uptake and the digestive functions of the worm are disrupted to such an extent that an autolytic process occurs.
Following oral administration, approximately 20% of the dose reaches the systemic circulation, due to incomplete absorption and to extensive pre-systemic metabolism (first- pass effect). Maximum plasma concentrations are generally seen 2 to 4 hours after administration. Dosing with a high fat meal leads to a modest increase in the bioavailability of mebendazole.
The plasma protein binding of mebendazole is 90 to 95%. The volume of distribution is 1 to 2 L/kg, indicating that mebendazole penetrates areas outside the vascular space. This is supported by data in patients on chronic mebendazole therapy (e.g. 40mg/kg/day for 3-21 months) that show drug levels in tissue.
Orally administered mebendazole is extensively metabolized primarily by the liver. Plasma concentrations of its major metabolites (amino and hydroxylated amino forms of mebendazole) are substantially higher than those of mebendazole. Impaired hepatic function, impaired metabolism, or impaired biliary elimination may lead to higher plasma levels of mebendazole.
Mebendazole, the conjugated forms of mebendazole, and its metabolites likely undergo some degree of enterohepatic recirculation and are excreted in the urine and bile. The apparent elimination half-life after moral dose ranges from 3 to 6 hours in most patients.
During chronic dosing (e.g. 40mg/kg/day for 3-21 months), plasma concentrations of mebendazole and its major metabolites increase, resulting in approximately 3- fold higher exposure at steady-state compared to single dosing.
Pre-clinical safety data
The single-dose toxicity evaluations in multiple species revealed that mebendazole was well tolerated and has a large margin of safety. Repeated-dose, oral, chronic toxicity results in rats, at toxic dose levels of 40 mg/kg and above, showed altered liver weights with some slight centrilobular swelling and hepatocellular vacuolation, and altered testicular weights with some tubular degeneration, desquamation and marked inhibition of spermatogenic activity. No carcinogenic effects were observed in the mouse or rat. No mutagenic activity was shown in in vitro gene-mutagenicity studies. In vivo tests revealed no structural chromosome damaging activity. Micronucleus test results have shown aneugenic effects in mammalian somatic cells above a threshold plasma concentration of 115 mg/ml. At maternal toxic doses, embryotoxic and teratogenic activity has been shown in pregnant rats at a single dose of 10 mg/kg and above. Teratogenic and fetotoxic effects have also been observed in mice at maternally toxic doses of 10 mg/kg and higher. No harmful effects on reproduction were noted in other animal species tested.
List of Excipients
The inactive ingredients of the tablets are lactose, methylcellulose, sodium starch glycolate, microcrystalline cellulose, corn starch, magnesium stearate, colloidal silicon dioxide.
Special Precautions for Storage
Store between 15 and 30oC.
Keep out of reach of children.
Nature and Contents of Container
CHIMOX 500mg is supplied in packs containing one tablet.
Chi Pharmaceuticals Ltd.
14 Chivita Avenue
Ajao Estate, Lagos, Nigeria.