ORNA Infusion

 Ornidazole Infusion 500 mg/100ml (For IV Infusion only)

COMPOSITION

Each 100 ml contains:

Ornidazole                  IP        500 mg

Water for Injections   BP           q.s.

DESCRIPTION

A clear, colourless to slightly pale-yellow colored solution.

 PHARMACODYNAMIC

Pharmacotherapeutic group: Antibacterials for systemic use; Imidazole derivatives.

ATC code: J01X D03

5-nitroimidazoles belongs to the nitro heterocyclic family of compounds widely used for the treatment or prophylaxis of infections due to anaerobic bacteria and protozoa. They have also received much attention in cancer therapy as radio sensitizers of hypoxic tumors and by their direct cytotoxic effects towards hypoxic cells. Nitroimidazoles are thought to produce their bactericidal activity through four phases:

(I) Entry into the bacterial cell

(II) Nitro group reduction

(III) Action of the cytotoxic by products

(IV) Production of inactive end products

Bactericidal activity appears to be dependent on the formation of a redox intermediate metabolite in the bacterium. This toxic metabolite may interact primarily with DNA, RNA or intracellular proteins; however, its main effects are DNA strand breakage, inhibited repair and ultimately disrupted transcription and cell death. Owing to its similar chemical properties, Ornidazole shares the same mechanism of action and spectrum of microbiological activity as other nitro imidazole agents against anaerobes and protozoa. Therefore, it is a drug of choice for treatment of a large variety of diseases, including intra-abdominal, pulmonary and brain abscesses, chronic sinusitis and otitis, and genital tract infections.

 PHARMACOKINETICS

Absorption

The absolute bio-availability of Ornidazole is >90 percent administered dose.

Distribution

Ornidazole is widely distributed in body tissues and fluids, including cerebro spinal fluid. Antibacterial concentrations are achieved in vaginal secretions, appendix and intestinal tissues. Ornidazole concentrations have been measured in the colonic (8.7μg/g) and abdominal (3.6 to 4.4 μg/g) walls and epiploic fat (3.4 to 4.7μg/g) throughout colorectal surgery in those receiving a 1 g intravenous dose for surgical prophylaxis. Although ornidazole concentrations in cerebrospinal fluid have only been assessed in animal models, it is expected that it should penetrate the central nervous system.

Biotransformation

Ornidazole is extensively metabolized in the liver before excretion by renal pathway. Ornidazole is largely excreted in the urine and to a lesser extent in the faeces, mainly as conjugates and metabolites. Only 4% of unchanged drug was excreted in the urine.

 Elimination

The plasma elimination half-life of ornidazole is 11 to 14 hours with AUC values for single intravenous 500 mg doses of 185 mg/L.h and for 1 g doses of 375 mg/L.h. The mean Cl value of ornidazole is 47 mL/min (2.82 L/h) for 1 g intravenous dose.

THERAPEUTIC INDICATION

• Anerobic systemic infections caused by Ornidazole –sensitive microflora: septicemia, meningitis, peritonitis, post-operative wound infections, post-natal sepsis, septic abortion and endometritis.
• Prevention of infections caused by anaerobic bacteria, during operative treatment (especially middle and straight intestine surgeries) gynaecological surgeries.
• Severe intestinal ameobiasis, all extra-intestinal amoebiasis forms, giardiasis, liver abscess.

 DOSAGE AND ADMINISTRATION

Ornidazole is given to patients in doses of 20 mg/kg BW (body weight) per day in two separate

doses for the treatment. Mechanism of action could be related either to its action against anaerobes or on the immune system. Ornidazole is one of the most frequently used antibiotics

for curing Helicobacter pylori infection. In the treatment, 500 mg Ornidazole is used with 30 mg lansoprazole and 1 g Amoxicillin.

OVERDOSE

No specific counter measures after accidental overdose are recommended. In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Symptoms: loss of consciousness, headache, vertigo, trembling, convulsions, depression, peripheral nephritis, nausea, vomiting. Treatment: symptomatic treatment, specific antidote unknown.

CONTRAINDICATION

• Hypersensitivity to any of the drug components
• Organic central nervous system diseases;
• Epilepsy, disseminated sclerosis;
• Circulation disorders;
• Chronic alcoholism;
• First pregnancy trimester and lactation;
• Body mass under 6 kg.

 WARNING AND PRECAUTIONS

Caution should be exercised in patients with diseases of the CNS, e.g., epilepsy or multiple sclerosis. A health risk exists, among others, in patients with liver disease, in alcoholics, epileptics, in patients with brain damage, in pregnant and nursing women, and children, if the special dosage for children is exceeded. The effect of other medicines can be intensified or impaired. Nitro-imidazoles are generally considered mutagenic chemicals.

The nitrogen group present in nitroimidazole derivatives is considered responsible for the mutagenicity of these compounds. In a study, mutagenicity was observed with Klebsiella pneumoniae and Salmonella typhimurium Ornidazole was revealed to be mutagenic in Salmonella typhimurium, but negative results have been observed in other tests, such as micro nucleus in mice and chromosome aberrations. Long-term carcinogenicity studies were also conducted with ornidazole (high dose 400 mg/kg/day) by administering in rats for two years. At the end of this study no carcinogenicity was recorded for ornidazole.

PREGNANCY, LACTATION AND ABILITY TO DRIVE

Like other nitro-imidazoles, ornidazole is widely distributed in the body, cross the placenta and

appears in breast milk.

When administered during pregnancy: No teratogenic effect was observed with ornidazole in mice, rats and rabbits. Local and systemic tolerability of ornidazole was excellent in humans when used in pregnancy, and patients showed complete remission without premature delivery.

Children born to the trial patients showed normal initial development and their growth was normal. There was no evidence of ornidazole accumulation, and the pharmacokinetic parameters were very similar to those seen in healthy subjects. Therefore, dosage regimen requires no adjustment during pregnancy.

Fertility: Ornidazole has the advantage of fewer side effects in rats in which species its anti- fertility action has been documented, it has contraceptive properties in male, but not female, rats. It produces infertility by inhibiting epididymal sperm motility in terms of decreased sperm

velocity. These effects are rapidly reversible after the cessation of treatment.

Effects on ability to drive and use machines

Effects on ability to drive and use machines Somnolence, dizziness, tremor, rigidity, poor coordination, seizures, vertigo, or temporary loss of consciousness may occur in patients receiving Ornidazole. If they occur, such effects may affect tasks requiring alertness including the patient’s ability to drive.

DRUG INTERACTION

Ornidazole potentiates the effect of the coumarine range oral anticoagulants, which requires appropriate adjustment of the dose of the latter. Ornidazole prolongs the myo-relaxing effect of vecuronium bromide. The drug’s concentration is lowered in case of concurrent administration of microsomal enzyme inducers (phenobarbital, rifampicin) and increases in case of concurrent administration of liver microsomal system inhibitors, particularly H2-receptor blockers (cimetidine). Isolated cases of peripheral nephritis, psychic depression and epilepsy-like convulsions were reported in cases of concurrent use of other 5-nitroimidazole derivatives.

Alcoholism: Ornidazole, the therapeutic use of which is quite distinct from the treatment of chronic alcoholism, may produce a disulfram-like reaction with alcohol (flushing of the face and neck, palpitations, dizziness, nausea, etc.) in some cases.

The mechanism of this reaction is thought to be related with an inhibition of acetaldehyde dehydrogenase. Patients should be warned against the possibility of interactions with alcohol.

ADVERSE EFFECTS

Serious and Otherwise Important Adverse Reactions The following serious and otherwise

important adverse reactions are as follows Tendinopathy and Tendon Rupture.

• QT Prolongation
• Hypersensitivity Reactions
• Other Serious and Sometimes Fatal Reactions
• Central Nervous System Effects
• Clostridium Difficile-Associated Diarrhoea
• Peripheral Neuropathy
• Photosensitivity/Phototoxicity
• Development of Drug-Resistant Bacteria

 PRESENTATION

ORNA Infusions are supplied in 100 ml Flint, ISO Type II, Moulded infusion vial.

STORAGE AND OTHER INFORMATION

Store in a cool and dry place. Protect from light.

Store at below 30°C temperature.

Caution: Not to be used if container is found leaking or solution is hazy or contain any visible solid particles. Keep this medicine out of the sight and reach of children.