- OTSUZOL

Composition:
Each 100ml bottle contains 500mg of Metronidazole B.P. (0.5%W/V).
 
Pharmaco-therapeutic class: Anti-infective
 
Therapeutic indications:
OTSUZOL I.V. is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected to be the cause. OTSUZOL I.V. is active against a wide range of pathogenic micro-organisms notably species of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella vaginalis.
 
It is indicated in

• The prevention of postoperative infections due to anaerobic bacteria, particularly species of Bacteroides and anaerobic Streptococci.
• The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, necrotizing pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, and postoperative wound infections from which pathogenic anaerobes have been isolated.

 
Dosage and administration:
Treatment of Anaerobic Infections
The recommended dosage schedule for adults is:

• Loading Dose: 15 mg/kg infused over one hour (approximately 1 g for a 70-kg adult).
• Maintenance Dose: 7.5 mg/kg infused over one hour every six hours (approximately 500 mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose.
  • In elderly patients the pharmacokinetics of metronidazole may be altered and therefore monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.
  • For patients with severe hepatic impairment (Child-Pugh C), the metronidazole dose should be reduced by 50%.
  • In patients receiving Metronidazole Injection in whom gastric secretions are continuously removed by nasogastric aspiration, sufficient metronidazole may be removed in the aspirate to cause a reduction in serum levels.
  • The dose of Metronidazole Injection should not be specifically reduced in anuric patients since accumulated metabolites may be rapidly removed by dialysis.

A maximum of 4 g should not be exceeded during a 24-hour period. The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract and endocardium may require longer treatment.
Prophylaxis
For surgical prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery, the recommended dosage schedule for adults is:

1. 15 mg/kg infused over 30 to 60 minutes and completed approximately one hour before surgery; followed by
2. 7.5 mg/kg infused over 30 to 60 minutes at 6 and 12 hours after the initial dose.

It is important that (1) administration of the initial preoperative dose be completed approximately one hour before surgery so that adequate drug levels are present in the serum and tissues at the time of initial incision, and (2) Metronidazole Injection, be administered, if necessary, at 6-hour intervals to maintain effective drug levels. Prophylactic use of Metronidazole Injection, should be limited to the day of surgery only, following the above guidelines.
 
Contraindications:
Metronidazole injection is contraindicated in patients with prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
 
Warnings and Precautions:

• Patients with hepatic impairment metabolize metronidazole slowly, with resultant accumulation of metronidazole in the plasma. For patients with severe hepatic impairment (Child-Pugh C), a reduced dose of Metronidazole Injection, USP is recommended. For patients with mild to moderate hepatic impairment, no dosage adjustment is needed but these patients should be monitored for metronidazole associated adverse events.
• Patients with end-stage renal disease may excrete metronidazole and metabolites slowly in the urine, resulting in significant accumulation of metronidazole metabolites. Monitoring for metronidazole associated adverse events is recommended.
• Metronidazole should be used with caution in patients with active or chronic severe peripheral and central nervous system diseases due to the risk of neurological aggravation.
• Patients should be advised not to take alcohol during metronidazole therapy and for at least one day afterwards because of the possibility of a disulfiram-like (Antabuse effect) reaction.
• If for compelling reasons, metronidazole must be administered longer than the usually recommended duration, it is recommended that hematological tests, especially leukocytes count should be carried out regularly and that patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paresthesia, ataxia, dizziness, convulsive seizures).
• Patients should be warned that metronidazole may darken urine (due to metronidazole metabolite).
• Administration of solutions containing sodium ions may result in sodium retention. Care should be taken when administering metronidazole injection to patients receiving corticosteroids or to patients predisposed to edema.

 
 
 
Pregnancy: As metronidazole crosses the placental barrier and as its effects on human fetal organogenesis are not known, its use in pregnancy should be carefully evaluated.
 
Lactation: As metronidazole is excreted in human milk, unnecessary exposure to the drug should be avoided.
 
Driving a vehicle or performing other hazardous tasks:
Patients should be warned about the potential for confusion, dizziness, hallucinations, convulsions or transient visual disorders, and advised not to drive or operate machinery if these symptoms occur.
 
Interactions:
Disulfiram: psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.
Alcohol: alcoholic beverages and drugs containing alcohol should not be consumed during therapy and for atleast one day afterward because of a possibility of a disulfiram like reaction (antabuse effect: flushing, vomiting and tachycardia)
Oral anticoagulant therapy (warfarin type): potentiation of the anticoagulant effect and increased hemorrhagic risk caused by decreased hepatic catabolism. In case of coadministration, prothrombin time should be more frequently monitored and anticoagulant therapy adjusted during treatment with metronidazole.
Lithium: Plasma levels of lithium may be increased by metronidazole. Plasma concentration of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.
Cyclosporin: risk of elevation of cyclosporin serum levels. Serum cyclosporin and serum creatinine should be closely monitored when coadministration is necessary.
Phenytoin or Phenobarbital: increased elimination of metronidazole resulting in reduced plasma levels.
5 Fluorouracil: reduced clearance of 5 fluorouracil resulting in increased toxicity of 5 fluorouracil.
Busulfan: Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity.
 
Adverse Reactions:
Gastrointestinal effects: Epigastric pain, nausea, vomiting, diarrhea, oral mucositis, taste disorders, anorexia, Exceptional and reversible cases of pancreatitis.
Hypersensitivity reactions: Rash, pruritus, flushing, urticarial, Fever, angioedema, exceptional anaphylactic shocks, Very rare pustular eruptions.
Peripheral and central nervous system: Peripheral sensory neuropathy, Headache, convulsions, dizziness, Very rare reports of encephalopathy (e.g. confusion) and subacute cerebellar syndrome (e.g. ataxia, dysathria, gait impairment, nystagmus, and tremor), which may resolve with discontinuation of the drug.
Psychiatric disorders: Psychotic disorders including confusion, hallucinations.
Vision disorders: Transient vision disorders such as diplopia, myopia.
Hematology: Very rare cases of agranulocytosis, neutropenia and thrombocytopenia have been reported.
Liver: Very rare cases of reversible abnormal liver function tests and cholestatic hepatitis sometimes with jaundice have been reported.
 
Overdose:
Symptoms were limited to vomiting, ataxia and slight disorientation. Single oral doses of metronidazole up to 12g have been reported in suicide attempts and accidental overdose.
 
Management of Overdose:
There is no specific antidote for metronidazole over dosages. In case of suspected massive over dosages, a symptomatic and supportive treatment should be instituted.
 
Storage and instructions:
Store below 30°C.
Keep away from light.
Keep medicines out of the reach of children.
 
Special instructions:
Intravenous Infusion: Do not use if bottle is leaking, solution is cloudy or contains foreign matter.
 
Presentation:
OTSUZOL I.V. Infusion: Solution for intravenous infusion in 100 ml LLDPE bottle.
 
Manufactured by:
OTSUKA Pakistan Limited
F/4-9, H.I.T.E., HUB,
Baluchistan, Pakistan