Ofal M

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)

Ofloxacin Eye: It is used for the treatment of external ocular infections such as acute & sub-acute conjunctivitis, keratitis, kerato-conjunctivitis, blepharo-conjunctivitis, blepharitis, corneal ulcer and pre-operative prophylaxis in ocular surgery.

Ofloxacin Ear: It is used for the treatment of external ear infections (otitis externa) and certain middle ear infections (otitis media).

Ofloxacin Oral/Injection are used for the treatment of adults with mild to moderate infections caused by susceptible strains.

• Lower Respiratory Tract: Acute bacterial exacerbation of chronic bronchitis lung abscess, pneumonia.
• Gastrointestinal Tract: Enteric fever, shigellosis.
• Multi-drug-resistant Tuberculosis.
• Skin and skin structures: Uncomplicated skin and skin structure infections.
• Sexually Transmitted Diseases: Acute, Uncomplicated urethral and cervical gonorrhoea. Nongonococcal urethritis and cervicitis. Mixed infections of the urethra and cervix.
• Urinary tract: Uncomplicated Urinary Tract Infections, Complicated urinary tract infections.

Ofal M 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 InfectionsAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Acute Otitis Media, Bacterial Infections, Cervicitis, Community Acquired Pneumonia (CAP), Complicated Urinary Tract Infection, Conjunctivitis, Epididymitis, Hansen's Disease, Nongonococcal urethritis, Otitis Externa, Prostatitis, Skin and Subcutaneous Tissue Bacterial Infections, Spontaneous Bacterial Peritonitis (SBP), Traveler's Diarrhea, Ulcerative keratitis, Acute Pelvic inflammatory disease, Acute, uncomplicated Gonorrhea, Chronic suppurative Otitis media, Uncomplicated Cystitis

How Ofal M 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.

Ofloxacin acts on DNA gyrase and toposiomerase IV, enzymes which, like human topoisomerase, prevents the excessive supercoiling of DNA during replication or transcription. By inhibiting their function, the drug thereby inhibits normal cell division.

Dosage

Ofal M 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

Ofloxacin Eye: Instill 1 drop in the affected eye(s) every 2 to 4 hours for the first two days and then 4 times daily. The length of treatment should not exceed ten days.

Ofloxacin Ear: Instill 1-2 drops in the affected ear(s) twice daily or as needed.

Ofloxacin Intravenous (Adult):

• Skin and soft tissue infections: 400 mg bid infused over at least 1 hr.
• Complicated urinary tract infections: 200 mg daily by infusion over at least 30 min. Max: 400 mg bid infused over at least 1 hr.
• Lower respiratory tract infections, Septicaemia: 200 mg bid by infusion over at least 30 min. Max: 400 mg bid infused over at least 1 hr.

Ofloxacin Oral (Adult):

General dosage recommendations: The dose of ofloxacin is determined by the type and severity of the infection. The dosage range for adults is 200 mg to 800 mg daily. Up to 400 mg may be given as a single dose, preferably in the morning, larger doses should be given as two divided doses. Ofloxacin tablets should be swallowed with liquid; they should not be taken within two hours of intake of magnesium/aluminium containing antacids or iron preparations since reduction of absorption of ofloxacin can occur.

• Enteric fever: For adults 200 mg, every 12 hours, for 5 days. For children 15 mg/kg/day in 2 divided doses for 3 days.
• Shigellosis: 400 mg single dose.
• Multi-drug-resistant tuberculosis: 400 mg twice daily along with conventional anti-tuberculosis drugs.
• Lower respiratory tract infection: 400 mg daily, increasing, if necessary, to 400 mg twice daily.
• Uncomplicated Urinary Tract Infections: A single dose of 200/400 mg.
• Uncomplicated urethral and cervical gonorrhoea: A single dose of 400 mg.
• Non-gonococcal urethral and cervicitis: 400 mg daily in single or divided doses.
• Complicated Urinary Tract Infection: 200/400 mg/day for 7 days.

Children: Ofloxacin is usually not indicated for use in children or growing adolescents.

Elderly: No adjustment of dosage is required in the elderly.

May be taken with or without food. Avoid antacids or supplements containing Fe or Zn within 2 hr before or after ofloxacin. Ensure adequate hydration.

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.

Ofloxacin Eye: Transient ocular irritation, burning, stinging, redness, itching or photophobia have been reported.

Ofloxacin Ear: Mild irritation or mild discomfort in the ear may occur. Symptoms of an allergic reaction include rash, itching, swelling or trouble breathing.

Ofloxacin tablet or injection is generally well tolerated and clinical side-effects of ofloxacin has been quite low. Among the adverse effects gastrointestinal and central nervous systems' reactions are common. Nausea, rash, vomiting, abdominal pain, diarrhoea and gastrointestinal distress are the gastrointestinal adverse effects. Common central nervous system reactions are headache, dizziness and insomnia.

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.

LD₅₀=5450 mg/kg (orally in mice)

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.

Patients being treated with Ofloxacin should not expose themselves unnecessarily to strong sunlight and should avoid UV rays. Caution is recommended if the drug is to be used in psychotic patients or in-patients with a history of psychiatric disease.

Prolonged use of eye drops & ear drops may result in overgrowth of non-susceptible organisms and secondary infection respectively.

Interaction

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

Antacids containing magnesium, aluminium or calcium may decrease absorption of ofloxacin. Iron or Zinc may decrease oral absorption of ofloxacin.

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.

Bioavailability of ofloxacin in the tablet formulation is approximately 98%

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.

9 hours

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.

Ofloxacin is mainly eliminated by renal excretion, where between 65% and 80% of an administered oral dose of ofloxacin is excreted unchanged via urine within 48 hours of dosing. About 4-8% of an ofloxacin dose is excreted in the feces and the drug is minimally subject to biliary excretion.

Pregnancy & Breastfeeding use

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

Use in pregnancy: There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in lactation: It is not known whether Ofloxacin is excreted in human milk. Cautions should be taken when Ofloxacin eye & ear drops is administered during lactation.

Contraindication

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

It is contraindicated in patients who are hypersensitive to Ofloxacin or any other component of Ofloxacin (Eye/Ear Drops).

Ofloxacin tablet injection should not be used in-patients with known hypersensitivity to 4-fluoroquinolone antibacterials. It is contraindicated in-patients with a history of epilepsy or with a lowered seizure threshold. Ofloxacin is usually contraindicated in children or growing adolescents and in pregnant or breast feeding women.

Special Warning

Renal Impairment:

• CrCl <20 and patients on haemodialysis or peritoneal dialysis: 100 mg 24 hrly following usual initial dose.
• CrCl 20-50: Reduce dose by half 24 hrly following usual initial dose.

Hepatic Impairment:Severe: Reduce dose. Max: 400 mg daily

Acute Overdose

Symptoms: Confusion, dizziness, impairment of consciousness, convulsive seizures, GI reactions (e.g. nausea, mucosal erosions).

Management: Symptomatic and supportive treatment. Remove any unabsorbed drug by gastric lavage or admin of adsorbants and Na sulfate. Antacids are recommended for protection of gastric mucosa. Elimination may be increased by forced diuresis.

Storage Condition

Store in a cool and dry place. Protect from light and moisture. Keep out of the reach of children

Store between 15-30° C. Protect from light.

Innovators Monograph

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