Bactyl

Bactyl Uses, Dosage, Side Effects, Food Interaction and all others data.

Metronidazole, a nitroimidazole has an extremely broad spectrum antiprotozoal and antimicrobial activities, with high activity against anaerobic bacteria and protozoa. Metronidazole is usually completely and rapidly absorbed after oral administration. The half-life in plasma is about 8 hours. About 10% of the drug is bound to plasma proteins. Metronidazole penetrates well into body tissues and fluids. The liver is the main site of metabolism. Both unchanged Metronidazole and metabolites are excreted in various proportions in the urine after oral administration.

Metronidazole treats amebiasis, trichomoniasis, and giardiasis, exerting both antibacterial and antiprotozoal activities. Metronidazole is an effective treatment for some anaerobic bacterial infections. Metronidazole has shown antibacterial activity against the majority of obligate anaerobes, however, during in vitro studies, it does not demonstrate significant action against facultative anaerobes or obligate aerobes. The nitro group reduction of metronidazole by anaerobic organisms is likely responsible for the drug's antimicrobial cytotoxic effects, causing DNA strand damage to microbes.

A note on convulsions and neuropathy and carcinogenesis

It is important to be aware of the risk of peripheral neuropathy and convulsions associated with metronidazole, especially at higher doses. If convulsions or numbness of an extremity occur, discontinue the drug immediately. Metronidazole has been found to be carcinogenic in mice and rats. The relevance to this effect in humans is unknown. It is advisable to only administer metronidazole when clinically necessary and only for its approved indications.

Nalidixic acid is a synthetic narrow spectrum antibacterial. It is bacteriostatic or bactericidal depending on the concentration. Nalidixic acid appears to act by inhibiting bacterial DNA synthesis, possibly by interfering with DNA polymerization. It is rapidly and completely absorbed from the G.I. Tract. Parent drug and active metabolites are distributed to most tissues specially to the kidney and to the urine.

Nalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor.

Bactyl
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Bactyl
Generic	Metronidazole + Nalidixic Acid
Type	Tablet, Syrup
Therapeutic Class
Manufacturer	J,k,pharma
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Metronidazole is used for:

All forms of amoebiasis (intestinal and extra-intestinal disease including liver abscess and that of symptomless cyst passers)
Trichomoniasis
Giardiasis
Bacterial vaginosis
Acute ulcerative gingivitis
Anaerobic infections including septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis etc.
Anaerobically-infected leg ulcers and pressure sores
Acute dental infections (e.g. acute pericoronitis and acute apical infections)
Surgical prophylaxis (prevention of postoperative infections due to anaerobic bacteria, particularly species of bacteroides and anaerobic streptococci
Chronic symptomatic peptic ulcer disease (as an agent of triple therapy to eradicate H. pylori-the most important aetiological factor of peptic ulcer)

Nalidixic acid is used for -

Urinary tract infections caused by susceptible Gram-negative microorganisms, including the majority of Proteus strains, Klebsiella, Enterobacter spp. and E. coli.
Gastrointestinal infections caused by Salmonella and Shigella.

Bactyl is also used to associated treatment for these conditions: Abscess, Intra-Abdominal, Acne Rosacea, Amebiasis, Anaerobic Infection, Bacteremia, Bacterial Endocarditis, Bacterial Peritonitis, Bacterial Vaginosis (BV), Balantidiasis, Bloodstream Infections, Bone and Joint Infections, Brain abscess, CNS Infection, Candidal Vulvovaginitis, Clostridium Difficile Infection (CDI), Empyema, Endometritis, Endomyometritis, Facial Rosacea, Giardiasis, Gynaecological infection, Helicobacter Pylori Infection, Infection, Bacteroides, Intraabdominal Infections, Lower Respiratory Infection, Lower respiratory tract infection bacterial, Lung Abscess, Meningitis, Mixed Vaginal Infections, Parasitic infection NOS, Periodontitis, Pneumonia, Postoperative Infections, Pouchitis, Septicemia bacterial anaerobic, Skin and Subcutaneous Tissue Bacterial Infections, Tetanus, Trichomonal Vaginitis, Trichomonas Vaginitis, Tubo-ovarian abscess, Urethritis, Vulvovaginitis, Asymptomatic Trichomoniasis, Entamoeba histolytica, Hepatic abscess, Refractory Sinusitis, Skin and skin-structure infections, Symptomatic Trichomoniasis, Asymptomatic InfectionsUrinary Tract Infection

How Bactyl works

The exact mechanism of action of metronidazole has not been fully established, however, it is possible that an intermediate in the reduction of metronidazole which is only made by anaerobic bacteria and protozoa, binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis. After administration, metronidazole enters cells by passive diffusion. Following this, ferredoxin or flavodoxin reduce its nitro group to nitro radicals. The redox potential of the electron transport portions of anaerobic or microaerophilic microorganisms renders metronidazole selective to these organisms, which cause nitro group reduction, leading to the production of toxic metabolites. These include N-(2-hydroxyethyl) oxamic acid and acetamide, which may damage DNA of replicating organisms.

Evidence exists for Nalidixic acid that its active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis.

Dosage

Bactyl dosage

Tablet and Suspension:

Amoebic dysentery: Duration 5-10 Days;

For Tablet: Adults- 750 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 800 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 200 mg q.i.d. (1-3 years) 200 mg t.i.d.

Asymptomatic amoebiasis: Duration 5-10 Days;

For Tablet: Adults- 500-750 mg t.i.d. Children- (7-10 years) 250-500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 500-800 mg t.i.d. Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Hepatic extraintestinal amoebiasis : Duration 5-10 Days (or 2days);

For Tablet: Adults- 500-750 mg t.i.d.; Children- (7-10 years) 250-500 mg t.i.d.; (3-7 years) 250 mg q.i.d.; (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 500-800 mg t.i.d.; Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Giardiasis: Duration 3 Days;

For Tablet: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 750 mg once daily; (1-3 years) 500 mg once daily.
For suspension: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 800 mg once daily; (1-3 years) 500 mg once daily.

Trichomoniasis: Duration 7 Days;

For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Trichomoniasis: Duration 1 Day;

For Tablet: Adults- 2 g single dose;
For Suspension: Adults- 2 g single dose;

Vincent's infection (Ulceration of mucous membrane of respiratory tract & mouth): Duration 3 Days;

For Tablet: Adults- 250 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Periodontal infection: Duration 3 Days;

For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Severe dental infection: Duration 3 Days;

For Tablet: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Anaerobic infection: Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.
For Suspension: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.

Postoperative anaerobic infection (specially in operation abdominal or gynecological surgery): Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.
For Suspension: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.

Bacterial vaginitis: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d.
For Suspension: Adults- 500 mg b.i.d.

Leg ulcers: Duration 1 Day;

For Tablet: Adults- 2 g as a single dose
For Suspension: Adults- 2 g as a single dose

Pressure sores: Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d.
For Suspension: Adults- 500 mg t.i.d.

H. pylori infection: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d
For Suspension: Adults-500 mg b.i.d

Antibiotic Associated Pseudomembranus colitis: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d
For Suspension: Adults- 500 mg b.i.d

Vaginal Gel:

The recommended dose is one applicator full of Metronidazole GEL (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole GEL should be administered at bedtime.

Suppository:

Anaerobic infections:

Adult: 1 g 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
Child: 5-10 yr 500 mg. All doses to be given 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

Prophylaxis of postoperative anaerobic bacterial infections:

Adult: 1 g 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
Child: 5-10 yr 500 mg 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

IV Infusion:

Metronidazole injection should be infused intravenously at an approximate rate of 5 ml/min. Oral medication should be substituted as soon as feasible. Treatment for 7 days should be satisfactory for most patients, but the physician might decide to prolong treatment.

For bacterial infections: Adults: 500 mg (100 ml) 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly.
For treatment before and during surgery: Adults: 500 mg (100 ml) shortly before operation, repeated 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly

Adults:

Initial: Oral 1 gm every 6 hours for 7 days reducing to 500 mg every 6 hours.

Infants and children 3 month of age and over:

Initial: Oral 13.75 mg/kg body weight every six hours for one or two weeks.
Maintenance: Oral 8.25 mg/kg body weight every six hours or as prescribed by the physician.

Should be taken with food.

Side Effects

Side effects of Metronidazole include gastrointestinal discomfort, nausea, coated tongue, dryness of mouth and unpleasant metallic or bitter taste, headache, pruritus and skin rashes and less frequently, vertigo, depression, insomnia, drowsiness, urethral discomfort, and darkening of the urine. Occasionally there may be temporary moderate leucopenia. Peripheral neuropathy has been reported in patients on prolonged therapy.

Gastro-intestinal disturbances including nausea, vomiting, diarrhoea, haemolysis in G6PD deficiency, allergic reaction including urticaria, rashes, fever, arthralgia, eosinophilia, also myalgia, muscle weakness, phototoxicity, jaundice, visual disturbances and convulsions.

Toxicity

LD50 information

The oral LD50 of metronidazole in rats is 5000 mg/kg

Overdose information

Adverse effects that may be exaggerated with an overdose include peripheral neuropathy, central nervous system toxicity, seizures, disulfiram-like effect (if combined with alcohol) dark urine, a metallic taste in the mouth, nausea, epigastric discomfort, and vertigo, in addition to neutropenia. There is no specific antidote for metronidazole overdose. Symptomatic and supportive treatment should be employed in addition to the administration of activated charcoal to remove the unabsorbed drug from the gastrointestinal tract. In addition to the above measures, contact the local poison control center for updated information on the management of a metronidazole overdose.

ORAL (LD₅₀): Acute: 1160 mg/kg [Rat]. 572 mg/kg [Mouse]. Toxic psychosis, convulsions, increased intracranial pressure, or metabolic acidosis may occur in patients taking more than the recommended dosage. Vomiting, nausea, and lethargy may also occur following overdosage.

Precaution

Metronidazole should not be used in patients with blood dyscrasia. It is suggested that it should not be given in the first three months of pregnancy. When given in conjunction with alcohol, Metronidazole may provoke a disulphiram like effect.

General: Should be used with caution in liver disease, epilepsy or severe cerebral arteriosclerosis patients. Periodic blood counts and renal and liver function tests should be performed if treatment is continued for more than 2 weeks. If bacterial resistance emerges, rapid change of drug should be made.

Children: Should not be used to infants less than 3 months of age.

Interaction

Metronidazole interacts with warfarin, nicoumalone, phenytoin, phenobarbitone, fluorouracil, disulfiram, lithium, cimetidine etc.

Concomitant use of Nalidixic acid with melphalan there have been reports of death froms severe blood containing diarrhoea caused by hemorrhagic ulcerative colitis. Probenecids inhibits tubular secretion of nalidixic acid and may therefore elevate serum concentration, possibly enhancing toxicity. Chlorpromazine and Perphenazine have been shown to potentiate the effect of Nalidixic Acid in vitro.

Volume of Distribution

Metronidazole is widely distributed throughout the body and various body fluids. They include the bile, saliva, breastmilk, cerebrospinal fluid, and the placenta. Steady-state volume distribution of metronidazole in adults ranges from 0.51 to 1.1 L/kg. It attains 60 to 100% of plasma concentrations in various tissues, such as the central nervous system, however, is not measured in high concentrations in the placental tissue.

Elimination Route

After the intravenous infusion of a 1.5g dose, peak concentration was reached within 1 hour and was peak level of 30-40 mg/L. When a multiple-dose regimen of 500mg three times a day administered intravenously, steady-state concentrations were achieved within about 3 days and peak concentration was measured at 26 mg/L. When administered orally in the tablet form, metronidazole is absorbed entirely absorbed, showing a bioavailability of greater than 90%. One resource indicates that Cmax after a single oral dose of 500mg metronidazole ranges from 8 to 13 mg/L, with a Tmax of 25 minutes to 4 hours. The AUC following a single 500mg oral dose of metronidazole was 122 ± 10.3 mg/L • h.

A note on the absorption of topical preparations

Insignificant percutaneous absorption of metronidazole occurs after the application of 1% metronidazole cream topically. Healthy volunteers applied one 100 mg dose of 14C-labelled metronidazole 2% cream to unbroken skin. After 12 hours, metronidazole was not detected in the plasma. Approximately 0.1% to 1% of the administered metronidazole was measured in the urine and feces.

Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.

Half Life

The elimination half-life of metronidazole is 7.3 ± 1.0 after a single 500mg IV dose in healthy subjects. Another resource indicates that the elimination half-life for metronidazole ranges from 6 to 10 hours.

1.1 to 2.5 hours in healthy adult patients, and up to 21 hours in patients with impaired renal function.

Clearance

Dose adjustments may be required in patients with hepatic impairment, as clearance is impaired in these patients. The clearance of metronidazole in the kidneys is estimated at 10 mL/min/1.73 m2. The total clearance from serum is about 2.1 to 6.4 L/h/kg.

Elimination Route

Metronidazole and metabolites are 60 to 80% eliminated in the urine, and 6-15% excreted in the feces.

Following oral administration, NegGram is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys. Approximately four percent of NegGram is excreted in the feces.

Pregnancy & Breastfeeding use

Not recommended during first & later trimesters. Breast feeding should be delayed until 48 hours after discontinuing metronidazole in the mother.

Pregnancy: There is the possibility that it may cause cartilage damage and as it is a DNA-gyrase inhibitor there is a possibility of causing DNA damage too. Nalidixic acid is excreted in breast milk and there is a report of hemolytic anaemia in a breast feed child of an azotemic mother.

Contraindication

Metronidazole is contraindicated in patients with prior history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.

Nalidixic Acid is contraindicated to known hypersensitivity to Nalidixic acid, history of convulsive disorders and patients with porphyria. Should be used with caution in patients with liver and renal disease. Also in glucose 6 - phosphate dehydrogenase deficiency.