NORTIZ (NORFLOXACIN & TINIDAZOLE TABLETS)

Indications

• Urinary tract infections
• Bacterial infections
• Prostatitis

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: The usual oral dosage for adults is 400 mg twice daily, taken at least 1 hour before or 2 hours after meals.

Mechanism of action

Norfloxacin exerts its bactericidal effect by inhibiting the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are crucial for bacterial DNA replication, transcription, repair, and recombination. The fluorine atom at the 6 position enhances its potency against Gram-negative organisms, while the piperazine moiety at the 7 position provides anti-pseudomonal activity. Additionally, norfloxacin prolongs the QT interval by blocking voltage-gated potassium channels, particularly the rapid component of the delayed rectifier potassium current I(Kr).

Pharmacodynamics

As a fluoroquinolone antibiotic, norfloxacin demonstrates a bactericidal effect through its high affinity binding to bacterial DNA gyrase, which facilitates the untwisting required for DNA replication. The drug is noted for its significantly greater affinity for bacterial enzymes compared to mammalian enzymes, ensuring selective action against bacteria.

Pharmacokinetics

Norfloxacin is well-absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is widely distributed in body tissues and fluids, including urine, where it achieves therapeutic concentrations. The drug undergoes hepatic metabolism and is primarily excreted via the kidneys. The half-life of norfloxacin ranges from 3 to 4 hours, necessitating multiple doses for effective therapy.

Contra-indications

• Hypersensitivity to norfloxacin or any of its components
• History of tendon disorders related to fluoroquinolone use
• Patients with a history of myasthenia gravis

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Rash
• Tendon rupture
• QT interval prolongation

Interactions

• Antacids containing magnesium, aluminum, or calcium may reduce the absorption of norfloxacin
• Concurrent use with other drugs that prolong the QT interval can increase the risk of cardiac arrhythmias
• Ciprofloxacin and other fluoroquinolones may increase the effects of warfarin

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of tendon injury, especially in older patients and those on concurrent corticosteroids
• Assess risk factors for QT prolongation before prescribing

Pregnancy

Norfloxacin should only be used in pregnancy if the benefit outweighs the risk, as it may affect fetal development.

Breast-feeding

Norfloxacin is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Oral tablet: 400 mg

Indications

• Intestinal amoebiasis
• Urogenital trichomoniasis
• Giardiasis

Dosage

Children: For children aged 1 month to 11 years, the dosage is 50–75 mg/kg once, with a maximum of 2 g per dose. For children aged 12 to 17 years, the dosage is 2 g for a single dose, which may be repeated once if necessary.

Adults: The usual adult dosage is 2 g taken orally as a single dose for urogenital trichomoniasis or giardiasis, and 1.5 g to 2 g once daily for 3 to 6 days for intestinal amoebiasis.

Mechanism of action

Tinidazole acts as a prodrug and antiprotozoal agent. Its nitro group is reduced in Trichomonas by a ferredoxin-mediated electron transport system, generating free nitro radicals that covalently bind to DNA, causing DNA damage and cell death. The exact mechanism of action against Giardia and Entamoeba species is not fully understood but is believed to be similar to that of Trichomonas.

Pharmacodynamics

Tinidazole demonstrates in vitro and clinical activity against Trichomonas vaginalis, Giardia duodenalis (also known as G. lamblia), and Entamoeba histolytica. It does not exhibit significant activity against most strains of vaginal lactobacilli, which are beneficial bacteria in the vaginal flora.

Pharmacokinetics

Tinidazole is well absorbed following oral administration, with peak plasma concentrations occurring within 0.5 to 3 hours. It is extensively distributed throughout body tissues and fluids. The drug undergoes hepatic metabolism and is eliminated primarily through the urine, with a half-life of approximately 12 to 14 hours. Clinical and laboratory monitoring is advised if treatment extends beyond 10 days.

Adverse effects

• Abdominal pain
• Decreased appetite
• Diarrhoea
• Headache
• Nausea
• Skin reactions
• Vertigo
• Vomiting

Precautions

• Clinical and laboratory monitoring is advised if treatment exceeds 10 days

Pregnancy

Manufacturer advises avoiding use in the first trimester.

Breast-feeding

Present in milk; the manufacturer advises avoiding breastfeeding during and for 3 days after stopping treatment.

Storage

Store below 25°C, protect from moisture.

Formulations

• Tinidazole 500 mg tablets
• Tinidazole oral suspension

Mechanism of action

The bactericidal action of Norfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. Norfloxacin is a broad-spectrum antibiotic agent that is shown to be effective against various Gram-positive and Gram-negative bacterial species. The fluorine atom at the 6 position increases potency against gram-negative organisms, and the piperazine moiety at the 7 position is responsible for anti-pseudomonal activity Norfloxacin usually is bactericidal in action. Like other fluoroquinolone anti-infectives, norfloxacin inhibits DNA synthesis in susceptible organisms via inhibition of type II DNA topoisomerases (DNA gyrase, topoisomerase IV). Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP).

Pharmacodynamics

Norfloxacin is a quinolone/fluoroquinolone antibiotic. Norfloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian.

Mechanism of action

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in <i>Trichomonas</i> by a ferredoxin-mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against <i>Giardia</i> and <i>Entamoeba</i> species is not known, though it is probably similar. The nitro group of tinidazole is reduced by cell extracts of Trichomonas. As a result of this reduction a free nitro radical is generated which may be responsible for the antiprotozoal activity. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known.

Pharmacodynamics

Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: <i>Trichomonas vaginalis</i>, <i>Giardia duodenalis</i> (also termed <i>G. lamblia</i>), and <i>Entamoeba histolytica</i>. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.