Trimetro IV Metronidazole Injection USP

Trimetro™ IV
Metronidazole Injection USP (5 mg/mL) (ISOTONIC)

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory.

 

COMPOSITION

Each 100 mL contains: Metronidazole USP 500 mg.

 

PHARMACOLOGY

Metronidazole is a nitroimidazole with antiprotozoal and antibacterial actions. It is highly effective against Trichomonas vaginalis, Entamoeba histolytica and Giardia Iamblia. It has a bactericidal action against pathogenic anaerobic bacteria, particularly Bacteroides spp and Fusobacterium spp.

Bacteria inhibited by concentrations of metronidazole as low as 3.1 mcg/mL and killed by concentratons of 6.3 mcg/mL include B. fragilis, B. melanin ogenious, Campylobacter fetus, C perfringens, Eubacterium, Peptococcus, Fusobacterium, Peptostreptococcus and Veilonella spp.

In the presence of mixed flora (both aerobes and anaerobes). Metronidazole acts synergistically with antibiotics effective against common aerobic pathogens.
Metronidazole alone has no direct activity against aerobes and facultative anaerobes.

 

PHARMACOKINETICS

Following an intravenous infusion (over 20 minutes) of 500 mg. Metronidazole, in patients with anaerobic infections serum concentrations achieved were 35.2 mcg/mL at 1 hour, 33.9 mcg/mL at 4 hours and 25.7 mcg/mL at 8 hours. The half life following a single intravenous dose is 6-7 hours. Metronidazole is only slightly bound to plasma proteins. It readily penetrates tissues and has a large apparent volume of distribution equivalent to distribution over 70-95% body weight.

It attains bactericidal concentrations in most tissues and body fluids including brain, CSF, abscess cavities, saliva, bile, vaginal secretions, amniotic fluid and breast milk.

Metabolism

Metronidazole is eliminated in man largely by metabolism resulting from side-chain oxidation, hydroxylation or conjugation of the parent compound. The major metabolic product is 1 – (2-hydroxyethyl) -2- hydroxymethyl -5- nitroimidazole which along with its glucuronide accounts for 40% to 50% of recovered urinary material. The acid and alcohol metabolites of Metronidazole are 50% and 30% as active respectively as metronidazole.

Excretion

Over a period of 24 hours urinary recovery of total nitro derivatives accounts for 35% to 65%. Renal clearance is 10.2 mL per min/1.75 sq.m. After intravenous administration of a low dose, 63% of the total radio activity is excreted in the urine and 6.2% in the faeces, over a 3 days period. In patients with a normal billary tract, the concentration of Metronidazole in gall bladder bile after an intravenous dose of 500 mg is significantly higher than in serum.

Influence of Disease on Kinetics

Accumulation of Metronidazole has been demonstrated in serum after continual doses in a patient with impaired renal function. Therefore, dosage frequency can be reduced in patients with severe renal insufficiency.

 

INDICATIONS

Trimetro IV is an isotonic formulation, composed of a superior grade of injectable Metronidazole specially developed by Unique’s R & D division in India, for intravenous administration in susceptible life threatening infections.

It is particularly suited for patients who cannot retain oral medication and for patients in whom desired serum concentrations have to be attained rapidly and reliably. Metronidazole injection is thus indicated for

I. Treatment of infections caused by Bacteroides fragilis and other species of Bacteroides like Fusobacteria, Eubacteria and Anaerobic cocci such as

a. Intra abdominal infections-appendicitis, cholecystitis, peritonitis, liver abscess and post-operative wound infection.

b. Gynaecological and obstetrical infections-puerperal sepsis, pelvic cellulitis, pelvic peritonitis.

c. Respiratory infections-necrotising pneumonia, empyema, lung abscess.

d. Central nervous system infections-meningitis, brain abscess.

e. Miscellaneous infections-septicaemia, gas gangrene, osteomyelitis.

II. Prevention of postoperative infections due to anaerobic bacteria

III. Treatment of amoebic abscess of the liver and in moribund or toxic cases of fulminating intestinal amoebiasis.

 

DOSAGE

Adults and Children over 12 years of age:

500mg (100 mL) infused over a period of 20 minutes at a rate of 5 mL/minute repeated 8 hourly.

Children below 12 years of age:

Depending upon clinical and bacteriological assessment, the physician may decide the duration of treatment.

Depending on the weight of the child the volume of fluid to be infused should be determined on the basis of 7.5 mg/kg. The rate of infusion as well as the frequency remains the same as in adults: 20 minutes at the rate of 5 mL/min repeated 8 hourly.

Oral medication should be substituted as soon as this becomes feasible (200-400 mg three times daily).

 

SIDE EFFECTS

Side effects have seldom been reported in patients treated with intravenous – Metronidazole. Further studies are needed to determine the frequency and nature of adverse effects likely to be encountered with higher dosage and greater duration of Metronidazole treatment, sometimes necessary for the treatment of severe anaerobic infections. Adverse effects which occur commonly with dosages of Metronidazole used to treat trichomoniasis and amoebiasis are anorexia, nausea, abdominal pain, vomiting, vertigo, tiredness and dark colouration of the urine.

Less commonly reported side effects are ataxia, headache, transient and reversible neutropenia, metallic taste, vaginal and urethral burning, gastric irritation, diarrhoea, furred tongue. Peripheral neuropathy has also occurred in a patient treated with Trimetro IV for anaerobic infection. Transient epileptiform seizures have been reported in a few patients undergoing intensive high dosage metronidazole treatment for radiosensitization.

 

PRECAUTIONS

As metronidazole is excreted in relatively high concentration in human breast milk, its use should be avoided in nursing mothers. It should be avoided, if possible, during first trimester of pregnancy, for its effects on foetal development are not definitely known. Being a nitro-imidazole derivative, moderate leucopenia has been reported in some patients. It is advisable to carry out total differential leucocyte count before, during and after treatment in patients requiring long term Metronidazoie therapy.

 

DRUG INTERACTIONS

1. Clinically significant interaction between Metronidazole and Warfarin has been reported. Metronidazole has been found to increase prothrombin time. It is preferable to discontinue oral anticoagulants 24 hours prior to administration of Trimetro IV.

2. Simultaneous administration of Metronidazole and disulfiram has been reported to cause acute psychosis and confusional state.

3. It is advisable to avoid mixing I.V. infusions of different drugs in keeping with this rule; Trimetro IV should not be mixed with any other drug.

 

DIRECTION FOR USE

1) The overwrap is a moisture barrier. The inner container maintains the sterility of the product. Do not remove inner container from overwrap until ready for use.

2) After removing overwrap, check for minute leaks by squeezing the container. Do not use if leaks are found and return for replacement.

3) Bring the injection bottle to room temperature or preferably to 37°C just before use.

4) Clean the spout of injection bottle with surgical spirit.

5) Keep the bottle on a table or on a hard surface and insert the cannula of the sterile infusion set into the spout of injection bottle (Please note that the cannula of the infusion set should be inserted fully and not half way into the spout of the Metronidazole I.V. bottle to avoid leakage).

6) For administration hang the bottle upside down.

7) Inject intravenously slowly at a rate of about 5 ml/minute.

8) To admit air, insert a sterile injection cannula on the top of the inverted bottle anywhere above the level of the liquid.

 

Warning: Even invisible damage to bottle caused during storage or transit, may result in contamination. Do not use if leak found on squeezing, or contents not clear, and return for replacement.

 

Caution: Admixture of 10.0% Dextrose, Penicilin G Potassium and Ringer. Lactate Solution to Trimetro IV Infusion is contraindicated because of chemical incompatibility.

 

PRESENTATION

100 mL bottles STERILE, NON-PYROGENIC ISOTONIC, SINGLE DOSE CONTAINER.

 

STORAGE

Store in a cool, dark place. Do not freeze.

 

Imported and Marketed in Nigeria by

M/s.TAH Pharmaceuticals Limited

38, Assembly Road, Satellite Town, Lagos, Nigeria

 

Manufactured by

UNIQUE PHARMACEUTICAL LABORATORIES.

(A Division of J. B. Chemicals & Pharmaceuticals Ltd.)

304-308, GIDC, Panoli, 394 116, India.

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