Ofloxacin

Ofloxacin belongs to the fluoroquinolone family and acts in a bactericidal way, meaning it kills the bacterium rather than merely slowing its growth. It inhibits two bacterial enzymes, DNA gyrase and topoisomerase IV, which are type II topoisomerases. These enzymes untangle, cut and rewind DNA so the bacterium can copy and read it. By blocking them, ofloxacin prevents the replication and transcription of bacterial DNA, and the bacterium can no longer divide.

These two targets are specific to bacteria, so the effect on the equivalent enzymes in our own cells remains weak. Ofloxacin covers both Gram-positive and Gram-negative bacteria, which explains its broad spectrum. This dual activity on DNA gyrase and topoisomerase IV makes it effective against many organisms responsible for common infections.

Taken orally, ofloxacin treats several bacterial infections. It is used in acute pyelonephritis, complicated urinary tract infections and uncomplicated cystitis, as well as in non-gonococcal urethritis and cervicitis and in gonococcal infections. It also serves during acute exacerbations of chronic obstructive pulmonary disease and in community-acquired pneumonia. The choice of indication and dose lies with the physician, according to the organism and the site of the infection.

After intake, oral absorption is rapid and almost complete: about one hour after a 200 mg dose, the plasma concentration reaches a peak close to 2.6 µg/ml. The elimination half-life is between 5.7 and 7 hours and does not depend on the dose. Elimination is mainly renal, since 80 to 90 % of the dose is found in the urine in unchanged form. In cases of severe renal impairment, the dosage is adjusted and the serum concentration monitored.

The tablet is swallowed whole with enough liquid, before or during a meal. The usual dose ranges from 200 to 800 mg per day: up to 400 mg can be taken all at once, preferably in the morning, and the maximum dose of 800 mg per day is split into two doses of 400 mg. Taking it regularly maintains an effective concentration throughout the treatment.

Ofloxacin should not be taken within the two hours surrounding a mineral antacid, sucralfate or a preparation containing aluminium, iron, magnesium or zinc, because these cations reduce its absorption. The treatment is followed until the end date set by the physician, even if symptoms improve before then, and it is not stopped on one’s own initiative.

The most frequent adverse effects, reported in at least 1 patient in 100, are first of all digestive and neurological. They include abdominal pain, diarrhoea, nausea and vomiting, as well as dizziness and headaches. These manifestations are the most common with the treatment.

A step below, between 1 case in 1,000 and 1 in 100, are the uncommon effects: anaemia, agitation, insomnia, drowsiness and paraesthesia, those sensations of tingling or numbness. Knowing their frequency helps to place what falls within the expected and what warrants mentioning to the physician.

Some effects are rare but call for particular vigilance. Tendinitis and tendon rupture, in particular of the Achilles tendon and sometimes on both sides, can occur, at times within the first 48 hours of treatment. Blood sugar disturbances have also been reported, both hypoglycaemia and hyperglycaemia, with cases of hypoglycaemic coma mainly in diabetic patients; in them, blood sugar monitoring is recommended. On the liver side, minor elevations of liver enzymes affect 1 to 3 % of patients receiving ciprofloxacin, norfloxacin or ofloxacin, while clinically overt liver injury remains rare, estimated at about 1 case per 100,000 exposures for the fluoroquinolone class.

Other rare effects include anaphylactic reactions, convulsions, hepatitis and Stevens-Johnson syndrome. Very rare effects include aneurysm or dissection of the aorta, heart valve regurgitation and acute renal failure. Their rarity does not remove the need to seek care promptly in the face of tendon pain, an extensive skin reaction or an unusual feeling of unwellness.

Several drug combinations call for caution. Theophylline and non-steroidal anti-inflammatory drugs lower the seizure threshold in the presence of quinolones and increase the risk of convulsions. With vitamin K antagonists such as warfarin, coagulation tests (PT and INR) and the risk of bleeding increase and must be monitored. With glibenclamide, ofloxacin can slightly raise plasma concentrations and requires blood sugar monitoring, and caution remains in order with medicines that prolong the QT interval.

The interaction with divalent and trivalent cations completes this picture. Iron, aluminium and calcium form complexes with ofloxacin and lower its bioavailability: to 67.4 % with ferrous sulfate, to 69.3 % with aluminium hydroxide and to 73.8 % with calcium carbonate, a chelation phenomenon that also concerns magnesium and zinc. Spacing out the doses is the recommended measure to preserve the antibiotic’s effectiveness. In the patient with renal impairment, dose adjustment and monitoring of the serum concentration round out the follow-up.