Ketoflox

A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Ketorolac tromethamine (Ketoflox) is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)

Ofloxacin (Ketoflox) Solution also contains benzalkonium chloride as inactive ingredient.

Ofloxacin (Ketoflox) is (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3,-de][1,4]benzoxazine-6-carboxylic acid.

Ofloxacin (Ketoflox) has a molecular formula of C₁₈H₂₀FN₃O₄, molecular weight of 361.37 and melting point of 260°-270°C (decomposition). Ofloxacin (Ketoflox) occurs as pale yellowish-white to light yellowish-white crystals or crystalline powder, is odorless and has a bitter taste. It is freely soluble in glacial acetic acid, sparingly soluble in chloroform, slightly soluble in water, methanol, ethanol and acetone and very slightly soluble in ethyl acetate. It is slowly colorized by light and has no specific rotation.

Partition Coefficient: Chloroform: 0.1 mol/L phosphate buffer (pH 7.4):4.95. N-Octanol: 0.1 mol/L phosphate buffer (pH 7):0.33.

pH: 6-7. Osmotic pressure ratio (to physiological saline) 1-1.2.

Carefully consider the potential benefits and risks of Ketorolac tromethamine (Ketoflox) and other treatment options before deciding to use Ketorolac tromethamine (Ketoflox). Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

Acute Pain in Adult Patients

Ketorolac tromethamine (Ketoflox) is indicated for the short-term (≤5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Therapy should always be initiated with intravenous or intramuscular dosing of Ketorolac tromethamine (Ketoflox), and oral Ketorolac tromethamine (Ketoflox) is to be used only as continuation treatment, if necessary.

The total combined duration of use of Ketorolac tromethamine (Ketoflox) injection and oral Ketorolac tromethamine (Ketoflox) is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses. Patients should be switched to alternative analgesics as soon as possible, but Ketorolac tromethamine (Ketoflox) therapy is not to exceed 5 days.

Ketorolac tromethamine (Ketoflox) injection has been used concomitantly with morphine and meperidine and has shown an opioid-sparing effect. For breakthrough pain, it is recommended to supplement the lower end of the Ketorolac tromethamine (Ketoflox) injection dosage range with low doses of narcotics prn, unless otherwise contraindicated. Ketorolac tromethamine (Ketoflox) injection and narcotics should not be administered in the same syringe.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ofloxacin (Ketoflox) tablets and other antibacterial drugs, Ofloxacin (Ketoflox) tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Ofloxacin (Ketoflox) tablets are indicated for the treatment of adults with mild to moderate infections (unless otherwise indicated) caused by susceptible strains of the designated microorganisms in the infections listed below. Please see DOSAGE AND ADMINISTRATION for specific recommendations.

Acute Bacterial Exacerbations of Chronic Bronchitis (ABECB) due to Haemophilus influenzae or Streptococcus pneumoniae.

Because fluoroquinolones, including Ofloxacin (Ketoflox), have been associated with serious adverse reactions, and for some patients ABECB is self-limiting, reserve Ofloxacin (Ketoflox) for treatment of ABECB in patients who have no alternative treatment options.

Community-Acquired Pneumonia due to Haemophilus influenzae or Streptococcus pneumoniae.

Uncomplicated Skin and Skin Structure Infections due to methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, or Proteus mirabilis.

Acute, Uncomplicated Urethral and Cervical Gonorrhea due to Neisseria gonorrhoeae.

Nongonococcal Urethritis and Cervicitis due to Chlamydia trachomatis.

Mixed Infections of the Urethra and Cervix due to Chlamydia trachomatis and Neisseria gonorrhoeae.

Acute Pelvic Inflammatory Disease (including severe infection) due to Chlamydia trachomatis and/or Neisseria gonorrhoeae.

NOTE: If anaerobic microorganisms are suspected of contributing to the infection, appropriate therapy for anaerobic pathogens should be administered.

Uncomplicated Cystitis due to Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa.

Because fluoroquinolones, including Ofloxacin (Ketoflox), have been associated with serious adverse reactions, and for some patients uncomplicated cystitis is self-limiting, reserve Ofloxacin (Ketoflox) for treatment of uncomplicated cystitis in patients who have no alternative treatment options.

Complicated Urinary Tract Infections due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter diversus,* or Pseudomonas aeruginosa.*

Prostatitis due to Escherichia coli.

* = Although treatment of infections due to this organism in this organ system demonstrated a clinically significant outcome, efficacy was studied in fewer than 10 patients.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to Ofloxacin (Ketoflox), USP. Therapy with Ofloxacin (Ketoflox), USP may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with Ofloxacin (Ketoflox), USP. Culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.

Treating eye pain and swelling following cataract surgery. It may also be used for other conditions as determined by your doctor.

Ketorolac tromethamine (Ketoflox) drops is a nonsteroidal anti-inflammatory drug (NSAID). It works by blocking the production of prostaglandin, a substance that causes pain and swelling.

Ofloxacin (Ketoflox) is used to treat certain bacterial infections in many different parts of the body. It may also be used for other problems as determined by your doctor. Ofloxacin (Ketoflox) may mask or delay the symptoms of syphilis. It is not effective against syphilis infections.

Ofloxacin (Ketoflox) belongs to the class of drugs known as fluoroquinolone antibiotics. It works by killing bacteria or preventing their growth. However, Ofloxacin (Ketoflox) will not work for colds, flu, or other virus infections.

Ofloxacin (Ketoflox) is available only with your doctor's prescription.

Carefully consider the potential benefits and risks of Ketorolac tromethamine (Ketoflox) and other treatment options before deciding to use Ketorolac tromethamine (Ketoflox). Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. In adults, the combined duration of use of IV or IM dosing of Ketorolac tromethamine (Ketoflox) and oral Ketorolac tromethamine (Ketoflox) is not to exceed 5 days. In adults, the use of oral Ketorolac tromethamine (Ketoflox) is only indicated as continuation therapy to IV or IM dosing of Ketorolac tromethamine (Ketoflox). See package insert for Ketorolac tromethamine (Ketoflox) tablets for transition from IV or IM dosing of Ketorolac tromethamine (Ketoflox) (single- or multiple-dose) to multiple-dose oral Ketorolac tromethamine (Ketoflox).

Note:

Oral formulation should not be given as an initial dose.

Use minimum effective dose for the individual patient.

Total duration of treatment in adult patients: the combined duration of use of IV or IM dosing of Ketorolac tromethamine (Ketoflox) and oral Ketorolac tromethamine (Ketoflox) is not to exceed 5 days.

Ketorolac tromethamine (Ketoflox) INJECTION

Ketorolac tromethamine (Ketoflox) injection may be used as a single or multiple dose on a regular or “prn” schedule for the management of moderately severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Hypovolemia should be corrected prior to the administration of Ketorolac tromethamine (Ketoflox). Patients should be switched to alternative analgesics as soon as possible, but Ketorolac tromethamine (Ketoflox) therapy is not to exceed 5 days.

When administering Ketorolac tromethamine (Ketoflox) injection, the IV bolus must be given over no less than 15 seconds. The IM administration should be given slowly and deeply into the muscle. The analgesic effect begins in ~30 minutes with maximum effect in 1 to 2 hours after dosing IV or IM. Duration of analgesic effect is usually 4 to 6 hours.

Single-Dose Treatment: The following regimen should be limited to single administration use only

IM Dosing

• Patients <65 years of age: One dose of 60 mg.
• Patients ≥65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 30 mg.

IV Dosing

• Patients <65 years of age: One dose of 30 mg.
• Patients ≥65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 15 mg.

Multiple-Dose Treatment (IV or IM)

• Patients <65 years of age: The recommended dose is 30 mg Ketorolac tromethamine (Ketoflox) injection every 6 hours. The maximum daily dose for these populations should not exceed 120 mg.
• For patients ≥65 years of age, renally impaired patients, and patients less than 50 kg (110 lbs): The recommended dose is 15 mg Ketorolac tromethamine (Ketoflox) injection every 6 hours. The maximum daily dose for these populations should not exceed 60 mg.

For breakthrough pain, do not increase the dose or the frequency of Ketorolac tromethamine (Ketoflox). Consideration should be given to supplementing these regimens with low doses of opioids “prn” unless otherwise contraindicated.

Pharmaceutical Information for Ketorolac tromethamine (Ketoflox) Injection

Ketorolac tromethamine (Ketoflox) injection should not be mixed in a small volume (e.g., in a syringe) with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride; this will result in precipitation of Ketorolac tromethamine (Ketoflox) from solution.

NOTE:

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Adults: Given orally in a usual daily dose of 300-600 mg of Ofloxacin (Ketoflox) (3-6 tabs) divided into 2-3 doses. If used for leprosy, it is recommended to give a total of 400-600 of Ofloxacin (Ketoflox) per day divided into 2-3 doses. In general, the dosage should be adjusted according to the causative organism and the severity of the symptoms. For leprosy, Ofloxacin (Ketoflox) should as a rule be co-administered with other antileprosy drugs.

Urinary Tract Infections: 1 x 100 mg up to 2 x 100 mg (or 1 x 200 mg).

Kidney and Reproductive Organ Infections: 2 x 100 mg up to 2 x 200 mg.

Respiratory Tract and Ear, Nose and Throat: 2 x 200 mg.

Skin and Soft Tissue Infections: 2 x 200 mg.

Bones and Joint Infections: 2 x 200 mg.

Abdominal Infections: 2 x 200 mg.

Septicaemia: 2 x 200 mg.

It is important that the individual doses be given at approximately equal intervals.

Depending on the severity of the infection and on the presence of complicating factors or pathogens of moderate susceptibility, it may be necessary to increase the dose to up 2 x 400 mg daily.

Patients with Impaired Renal Function: The initial dose is the same as for patients with normal renal function, whereas the maintenance dose should be reduced as follows: Creatinine clearance: 50-20 mL/min: 100-200 mg every 24 hrs; <20 mL/min: 100 mg every 24 hrs; haemodialysis or

Peritoneal dialysis:

Patients with Impaired Liver Function: The excretion of Ofloxacin (Ketoflox) may be reduced in patients with severe impairment of liver function (eg, cirrhosis with ascites). A maximum daily dose of 400 mg of Ofloxacin (Ketoflox) should therefore not be exceeded.

Duration of Treatment: The duration of treatment depends on the response of the causative organism and on the clinical picture. In most cases of acute infection, a course of treatment lasting 7-10 days is sufficient. In salmonelloses, the duration of treatment is usually 7-8 days, in shigelloses 3-5 days and in intestinal infections caused by E. coli 3 days.

For uncomplicated infections of the lower urinary tract, 3-day treatment is usually sufficient.

In case of infections with β-haemolytic streptococci (eg, purulent tonsillitis or erysipelas), treatment must be continued for at least 10 days in order to prevent late complications eg, rheumatic fever or inflammation of the renal glomeruli (glomerulonephritis). However, since β-haemolytic streptococci are of varying susceptibility to Ofloxacin (Ketoflox), treatment of such infections requires individual proof of susceptibility.

Until further experience is available, the duration of treatment should not exceed 2 months.

See also:
What is the most important information I should know about Ketorolac tromethamine (Ketoflox)?

Ketorolac tromethamine (Ketoflox) is contraindicated in patients with previously demonstrated hypersensitivity to Ketorolac tromethamine (Ketoflox).

Ketorolac tromethamine (Ketoflox) is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation and in patients with a history of peptic ulcer disease or gastrointestinal bleeding.

Ketorolac tromethamine (Ketoflox) should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

Ketorolac tromethamine (Ketoflox) is contraindicated as prophylactic analgesic before any major surgery.

Ketorolac tromethamine (Ketoflox) is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

Ketorolac tromethamine (Ketoflox) is contraindicated in patients with advanced renal impairment or in patients at risk for renal failure due to volume depletion.

Ketorolac tromethamine (Ketoflox) is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine musculature, thus increasing the risk of uterine hemorrhage.

Ketorolac tromethamine (Ketoflox) inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding.

Ketorolac tromethamine (Ketoflox) is contraindicated in patients currently receiving aspirin or NSAIDs because of the cumulative risks of inducing serious NSAID-related adverse events.

The concomitant use of Ketorolac tromethamine (Ketoflox) and probenecid is contraindicated.

The concomitant use of Ketorolac tromethamine (Ketoflox) and pentoxifylline is contraindicated.

Ketorolac tromethamine (Ketoflox) injection is contraindicated for neuraxial (epidural or intrathecal) administration due to its alcohol content.

See also:
What is the most important information I should know about Ofloxacin (Ketoflox)?

Hypersensitivity to 4-quinolone antibacterials, Ofloxacin (Ketoflox) or to any of the excipients of Ofloxacin (Ketoflox).

Patients with past history of tendonitis and epilepsy or with a lowered seizure threshold; since animal experiments do not entirely exclude the risk of damage to the cartilage of joints in the growing subject.

Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions when treated with quinolone antibacterial agents.

Use in pregnancy & lactation: The safety of Ofloxacin (Ketoflox) for use in human pregnancy has not been established. Reproduction studies performed in rats and rabbits did not reveal any evidence of teratogenicity, impairment of fertility or impairment of peri- and postnatal development. However, as with other quinolones, Ofloxacin (Ketoflox) has been shown to cause arthropathy in immature animals and therefore, its use during pregnancy is not recommended. Studies in rats have indicated that Ofloxacin (Ketoflox) is secreted in milk. It should therefore not be used during lactation.

Use in children: Ofloxacin (Ketoflox) is not indicated for use in children or growing adolescents.

Use Ketorolac tromethamine (Ketoflox) drops as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Ketorolac tromethamine (Ketoflox) drops. Talk to your pharmacist if you have questions about this information.
• Ketorolac tromethamine (Ketoflox) drops is only for the eye. Do not get it in your nose or mouth.
• To use Ketorolac tromethamine (Ketoflox) drops in the eye, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Do not blink. Remove excess medicine around your eye with a clean, dry tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.
• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.
• Each vial of Ketorolac tromethamine (Ketoflox) drops is intended for single use only. Throw away any unused medicine in the vial immediately after you have used your dose.
• If you will be using Ketorolac tromethamine (Ketoflox) drops to treat both eyes after surgery, do not use the same vial for both eyes. Doing so may increase the risk of passing an infection from one eye to the other.
• If you are using other eye medicines, wait at least 5 minutes before applying them to the eye.
• Do not wear contact lenses while you are using Ketorolac tromethamine (Ketoflox) drops. Take care of your contact lenses as directed by the manufacturer. Check with your doctor before you use them.
• Do not use Ketorolac tromethamine (Ketoflox) drops if it is discolored or contains particles.
• If you miss a dose of Ketorolac tromethamine (Ketoflox) drops and you are using it regularly, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Ketorolac tromethamine (Ketoflox) drops.

Use Ofloxacin (Ketoflox) solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Ofloxacin (Ketoflox) solution is only for the ear. Do not get it in your eyes, nose, or mouth.
• Before using, hold the ear drop container in your hand for 1 or 2 minutes to avoid dizziness that may result from putting cold drops into the ear. Lie down or tilt your head so that the affected ear faces up. For adults, gently pull the earlobe up and back to straighten the ear canal. For children, gently pull the earlobe down and back to straighten the ear canal. Drop the medicine into the ear canal. Keep the ear facing up for 5 minutes so the medicine can run to the bottom of the ear canal. A clean cotton plug may be gently inserted into the ear canal to prevent medicine from leaking out.
• To prevent germs from contaminating the medicine, do not touch the applicator to any surface, including the ear. Keep the container tightly closed.
• If you are using Ofloxacin (Ketoflox) solution for a middle ear infection, pump the flap over the ear 4 times after instilling the medicine in order to help it reach the middle ear.
• Ofloxacin (Ketoflox) solution works best if used at the same time each day.
• To clear up your infection completely, use Ofloxacin (Ketoflox) solution for the full course of treatment. Keep using it even if you feel better in a few days.
• If you miss a dose of Ofloxacin (Ketoflox) solution, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Ofloxacin (Ketoflox) solution.

Use: Labeled Indications

Pain, moderate to moderately severe: Short-term (up to 5 days) management of moderate to moderately severe pain in adults that requires analgesia at the opioid level.

Off Label Uses

Migraine

Data from a prospective, randomized, double-blind, double-dummy, placebo and active comparator, crossover, non-inferiority trial suggests that intranasal Ketorolac tromethamine (Ketoflox) may be beneficial for acute abortive treatment of migraine in patients with a history of episodic migraines for at least 1 year.

Use: Labeled Indications

Treatment of acute exacerbations of chronic bronchitis, community-acquired pneumonia, skin and skin structure infections (uncomplicated), urethral and cervical gonorrhea (acute, uncomplicated), urethritis and cervicitis (nongonococcal) due to Chlamydia trachomatis infection, mixed infections of the urethra and cervix, pelvic inflammatory disease (acute), cystitis (uncomplicated), urinary tract infections (complicated), prostatitis

Note: As of April 2007, the CDC no longer recommends the use of fluoroquinolones for the treatment of gonococcal disease.

Off Label Uses

Epididymitis

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines and the Canadian Guidelines on Sexually Transmitted Infections, Ofloxacin (Ketoflox) is an effective and recommended treatment option for acute epididymitis likely caused by enteric organisms (as monotherapy). The CDC guidelines also recommend Ofloxacin (Ketoflox) in combination with ceftriaxone for acute epididymitis likely caused by sexually transmitted chlamydia and gonorrhea and enteric organisms in men who practice insertive anal sex.

Leprosy (multibacillary)

Data from a limited number of patients in an open-label, parallel assessment study suggest that Ofloxacin (Ketoflox), in combination with rifampin and minocycline (ROM), may be beneficial for the treatment of multibacillary leprosy. Additional trials may be necessary to further define the role of multiple and single dose Ofloxacin (Ketoflox) regimens in paucibacillary leprosy. The World Health Organization Expert Committee on Leprosy and the National Hansen's Disease Program currently do not recommend Ofloxacin (Ketoflox) for the treatment of paucibacillary leprosy.

Spontaneous bacterial peritonitis (treatment)

According to national and international guidelines regarding treatment of spontaneous bacterial peritonitis (SBP), Ofloxacin (Ketoflox) may be considered as an alternative therapy to IV third-generation cephalosporins in patients with uncomplicated SBP who are not infected with a suspected quinolone-resistant organism. If fluoroquinolone-resistant, gram-negative bacteria are suspected as the causative organisms, when fluoroquinolones have been used for prophylaxis, or when patients are located in areas where incidence of quinolone-resistant bacterial infections are high, cefotaxime is the treatment of choice.

Traveler's diarrhea

Based on the Infectious Diseases Society of America Guidelines for the Practice of Travel Medicine and the American College of Gastroenterology (ACG) Guideline for the Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults, Ofloxacin (Ketoflox) is an effective and recommended fluoroquinolone for antibiotic treatment of traveler's diarrhea.

See also:
What other drugs will affect Ketorolac tromethamine (Ketoflox)?

When this drug applied simultaneously with:

- other NSAIDs may develop additive effects

- pentoxifylline, anticoagulants (heparin, including in low-dose) may increase the risk of bleeding

- ACE inhibitors may increase the risk of renal dysfunction

- probenecid increases the concentration of Ketorolac tromethamine (Ketoflox) in plasma and its half-life period

- lithium therapy may reduce renal clearance of lithium and increase its concentration in plasma

- furosemide - a decrease in its diuretic action.

During taking Ketorolac tromethamine (Ketoflox) the need for opioid analgesics to pain relief reduces.

See also:
What other drugs will affect Ofloxacin (Ketoflox)?

Drugs Known to Prolong QT Interval: Ofloxacin (Ketoflox), like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (eg, class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

Prolongation of bleeding time has been reported during concomitant administration of Ofloxacin (Ketoflox) and anticoagulants.

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold eg, theophylline. However, Ofloxacin (Ketoflox) is not thought to cause a pharmacokinetic interaction with theophylline, unlike some other fluoroquinolones.

Further lowering of the cerebral seizure threshold may also occur with certain nonsteroidal anti-inflammatory drugs.

In case of convulsive seizures, treatment with Ofloxacin (Ketoflox) should be discontinued.

Ofloxacin (Ketoflox) may cause a slight increase in serum concentrations of glibenclamide administered concurrently; patients treated with this combination should be closely monitored.

Vitamin K Antagonists: Coagulation tests should be monitored in patients treated with vitamin K antagonists because of a possible increase in the effect of coumarin derivatives.

Cimetidine: Cimetidine has demonstrated interference with the elimination of some quinolones. This interference has resulted in significant increases in t_½ and AUC of some quinolones. The potential for interaction between Ofloxacin (Ketoflox) and cimetidine has not been reported.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): The concomitant administration of a NSAID with a quinolone, including Ofloxacin (Ketoflox), may increasethe risk of CNS stimulation and convulsive seizures.

Probenecid: The concomitant use of probenecid with certain other quinolones has been reported to affect renal tubular secretion. The effect of probenecid on the elimination of Ofloxacin (Ketoflox) has not been reported.

Theophylline: Steady-state theophylline levels may increase when Ofloxacin (Ketoflox) and theophylline are administered concurrently. As with other quinolones, concomitant administration of Ofloxacin (Ketoflox) may prolong the t_½ of theophylline, elevate serum theophylline levels and increase the risk of theophylline-related adverse reactions.

Theophylline levels should be closely monitored and theophylline dosage adjustments made, if appropriate, when Ofloxacin (Ketoflox) is co-administered. Adverse reactions (including seizures) may occur with or without an elevation in the serum theophylline level.

Warfarin: Some quinolones have been reported to enhance the effects of the oral anticoagulant warfarin or its derivatives. Therefore, if a quinolone antimicrobial is administered concomitantly with warfarin or its derivatives, the prothrombin time or other suitable coagulation test should be closely monitored.

Antidiabetic Agents (eg, Insulin, Glyburide/Glibenclamide): Since disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concurrently with quinolones and an antidiabetic agent, careful monitoring of blood glucose is recommended when these agents are used concomitantly.

Cyclosporine: Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with some other quinolones. The potential for interaction between Ofloxacin (Ketoflox) and cyclosporine has not been reported.

Drugs Metabolized by Cytochrome P450 (CYP450) Enzymes: Most quinolone antimicrobial drugs inhibit CYP450 enzyme activity. This may result in a prolonged t_½ for some drugs that are also metabolized by this system (eg, cyclosporine, theophylline/methylxanthines, warfarin) when co-administered with quinolones. The extent of this inhibition varies among different quinolones.

Interactions with Laboratory Tests: Some quinolones, including Ofloxacin (Ketoflox), may produce false-positive urine screening results for opiates using commercially available immunoassay kits. Confirmation of positive opiate screens by more specific methods may be necessary.

See also:
What are the possible side effects of Ketorolac tromethamine (Ketoflox)?

Adverse reaction rates increase with higher doses of Ketorolac tromethamine (Ketoflox). Practitioners should be alert for the severe complications of treatment with Ketorolac tromethamine (Ketoflox), such as G.I. ulceration, bleeding and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions and liver failure. These NSAID-related complications can be serious in certain patients for whom Ketorolac tromethamine (Ketoflox) is indicated, especially when the drug is used inappropriately.

In patients taking Ketorolac tromethamine (Ketoflox) or other NSAIDs in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are:

Additional adverse experiences reported occasionally (<1% in patients taking Ketorolac tromethamine (Ketoflox) or other NSAIDs in clinical trials) include:

Body as a Whole: fever, infections, sepsis

Cardiovascular: congestive heart failure, palpitation, pallor, tachycardia, syncope

Dermatologic: alopecia, photosensitivity, urticaria

Gastrointestinal: anorexia, dry mouth, eructation, esophagitis, excessive thirst, gastritis, glossitis, hematemesis, hepatitis, increased appetite, jaundice, melena, rectal bleeding

Hemic and Lymphatic: ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia

Metabolic and Nutritional: weight change

Nervous System: abnormal dreams, abnormal thinking, anxiety, asthenia, confusion, depression, euphoria, extrapyramidal symptoms, hallucinations, hyperkinesis, inability to concentrate, insomnia, nervousness, paresthesia, somnolence, stupor, tremors, vertigo, malaise

Reproductive, female: infertility

Respiratory: asthma, cough, dyspnea, pulmonary edema, rhinitis

Special Senses: abnormal taste, abnormal vision, blurred vision, hearing loss

Urogenital: cystitis, dysuria, hematuria, increased urinary frequency, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure, urinary retention

Other rarely observed reactions (reported from postmarketing experience in patients taking Ketorolac tromethamine (Ketoflox) or other NSAIDs) are:

Body as a Whole: angioedema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema, myalgia

Cardiovascular: arrhythmia, bradycardia, chest pain, flushing, hypotension, myocardial infarction, vasculitis

Dermatologic: exfoliative dermatitis, erythema multiforme, Lyell's syndrome, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis

Gastrointestinal: acute pancreatitis, liver failure, ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease)

Hemic and Lymphatic: agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, post operative wound hemorrhage (rarely requiring blood transfusion — see Boxed WARNING, WARNINGS, and PRECAUTIONS)

Metabolic and Nutritional: hyperglycemia, hyperkalemia, hyponatremia

Nervous System: aseptic meningitis, convulsions, coma, psychosis

Respiratory: bronchospasm, respiratory depression, pneumonia

Special Senses: conjunctivitis

Urogenital: flank pain with or without hematuria and/or azotemia, hemolytic uremic syndrome

Postmarketing Surveillance Study

A large postmarketing observational, nonrandomized study, involving approximately 10,000 patients receiving Ketorolac tromethamine (Ketoflox), demonstrated that the risk of clinically serious gastrointestinal (GI) bleeding was dose-dependent. This was particularly true in elderly patients who received an average daily dose greater than 60 mg/day of Ketorolac tromethamine (Ketoflox).

See also:
What are the possible side effects of Ofloxacin (Ketoflox)?

Subjects with Otitis Externa

In the phase III clinical trials performed in support of once-daily dosing, 799 subjects with otitis externa and intact tympanic membranes were treated with Ofloxacin (Ketoflox) otic solution. The studies, which served as the basis for approval, were 020 (pediatric, adolescents and adults), 016 (adolescents and adults) and 017 (pediatric). The following treatment-related adverse events occurred in two or more of the subjects.

An unexpected increased incidence of application site reaction was seen in studies 016/017 and was similar for both Ofloxacin (Ketoflox) and the active control drug (neomycin-polymyxin B sulfate-hydrocortisone). This finding is believed to be the result of specific questioning of the subjects regarding the incidence of application site reactions.

In once daily dosing studies, there were also single reports of nausea, seborrhea, transient loss of hearing, tinnitus, otitis externa, otitis media, tremor, hypertension and fungal infection.

In twice daily dosing studies, the following treatment-related adverse events were each reported in a single subject: dermatitis, eczema, erythematous rash, follicular rash, hypoaesthesia, tinnitus, dyspepsia, hot flushes, flushing and otorrhagia.

Subjects with Acute Otitis Media with Tympanostomy Tubes (AOM TT) and Subjects with Chronic Suppurative Otitis Media (CSOM) with Perforated Tympanic Membranes

In phase III clinical trials which formed the basis for approval, the following treatment-related adverse events occurred in 1% or more of the 656 subjects with non-intact tympanic membranes in AOM TT or CSOM treated twice-daily with Ofloxacin (Ketoflox) otic solution:

Other treatment-related adverse reactions reported in subjects with non-intact tympanic membranes included: diarrhea (0.6%), nausea (0.3%), vomiting (0.3%), dry mouth (0.5%), headache (0.3%), vertigo (0.5%), otorrhagia (0.6%), tinnitus (0.3%), fever (0.3%). The following treatment-related adverse events were each reported in a single subject: application site reaction, otitis externa, urticaria, abdominal pain, dysaesthesia, hyperkinesia, halitosis, inflammation, pain, insomnia, coughing, pharyngitis, rhinitis, sinusitis, and tachycardia.

Post-marketing Adverse Events

Cases of uncommon transient neurospsychiatric disturbances have been included in spontaneous post-marketing reports. A causal relationship with Ofloxacin (Ketoflox) otic solution 0.3% is unknown.