Ofel Plus

Uses

Ketorolac injections and tablets are used for the short-term management of moderate to severe acute post-operative pain.

Ofloxacin Eye: It is used for the treatment of external ocular infections such as acute & sub-acute conjunctivitis, keratitis, kerato-conjunctivitis, blepharo-conjunctivitis, blepharitis, corneal ulcer and pre-operative prophylaxis in ocular surgery.

Ofloxacin Ear: It is used for the treatment of external ear infections (otitis externa) and certain middle ear infections (otitis media).

Ofloxacin Oral/Injection are used for the treatment of adults with mild to moderate infections caused by susceptible strains.

• Lower Respiratory Tract: Acute bacterial exacerbation of chronic bronchitis lung abscess, pneumonia.
• Gastrointestinal Tract: Enteric fever, shigellosis.
• Multi-drug-resistant Tuberculosis.
• Skin and skin structures: Uncomplicated skin and skin structure infections.
• Sexually Transmitted Diseases: Acute, Uncomplicated urethral and cervical gonorrhoea. Nongonococcal urethritis and cervicitis. Mixed infections of the urethra and cervix.
• Urinary tract: Uncomplicated Urinary Tract Infections, Complicated urinary tract infections.

Ofel Plus is also used to associated treatment for these conditions: Acute Migraine, Cystoid Macular Edema, Eye Pain, Inflammation, Ocular Itching, Pseudophakic Cystoid Macular Edema, Acute Pericarditis, Acute, moderate Pain, Acute, severe Pain, Chronic aphakic cystoid macular edema, Intraoperative miosis, Postoperative ocular painAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Acute Otitis Media, Bacterial Infections, Cervicitis, Community Acquired Pneumonia (CAP), Complicated Urinary Tract Infection, Conjunctivitis, Epididymitis, Hansen's Disease, Nongonococcal urethritis, Otitis Externa, Prostatitis, Skin and Subcutaneous Tissue Bacterial Infections, Spontaneous Bacterial Peritonitis (SBP), Traveler's Diarrhea, Ulcerative keratitis, Acute Pelvic inflammatory disease, Acute, uncomplicated Gonorrhea, Chronic suppurative Otitis media, Uncomplicated Cystitis

How Ofel Plus works

Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to it's mechanism of action. Although ketorolac is non-selective and inhibits both COX-1 and COX-2 enzymes, it's clinical efficacy is derived from it's COX-2 inhibition. The COX-2 enzyme is inducible and is responsible for converting arachidonic acid to prostaglandins that mediate inflammation and pain. By blocking this pathway, ketorolac achieves analgesia and reduces inflammation. Ketorolac is administered as a racemic mixture; however, the "S" enantiomer is largely responsible for it's pharmacological activity.

Ofloxacin acts on DNA gyrase and toposiomerase IV, enzymes which, like human topoisomerase, prevents the excessive supercoiling of DNA during replication or transcription. By inhibiting their function, the drug thereby inhibits normal cell division.

Dosage

Ofel Plus dosage

Ketorolac Tablet-

Ketorolac Tablet isrecommended for short-term use only (up to 7 days) and are not recommended for chronic use. 10 mg every 4 to 6 hours as required. Doses exceeding 40 mg/day are not recommended. For patients receiving parenteral Ketorolac tromethamine, and who are converted to Ketorolac tromethamine oral tablets, the total combined daily dose should not exceed 90 mg (60 mg for the elderly, renally impaired patients and patients less than 50 kg) and the oral component should not exceed 40 mg on the day the change of formulation is made. Patients should be converted to oral treatment as soon as possible.

Ketorolac injection-

Ketorolac injection may be used as a single or multiple doses, on a regular or when necessary schedule for the management of moderately severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting. When administering Ketorolac 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 within 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 (Adult):

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

IV Dosing (Adult):

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

IV or IM Dosing (2 to 16 years of age):

• IM Dosing: One dose of 1 mg/kg up to a maximum of 30 mg.
• IV Dosing: One dose of 0.5 mg/kg up to a maximum of 15 mg.

Multiple-Dose Treatment (IV or IM):

• Patients <65 years of age: The recommended dose is 30 mg Ketorolac injection every 6 hours. The maximum daily dose should not exceed 120 mg. Patients >65 years of age, renally impaired patients and patients less than 50 kg: The recommended dose is 15 mg Ketorolac 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.
• Conversion from Parenteral to Oral Therapy: Ketorolac tablets may be used either as monotherapy or as follow-on therapy to parenteral Ketorolac. When Ketorolac tablets are used as a follow-on therapy to parenteral Ketorolac, the total combined daily dose of ketorolac (oral + parenteral) should not exceed 120 mg in younger adult patients or 60 mg in elderly patients on the day the change of formulation is made. On subsequent days, oral dosing should not exceed the recommended daily maximum of 40 mg. Ketorolac IM should be replaced by Ketorolac tablet as soon as feasible. The total duration of combined parenteral andoral treatment should not exceed 5 days.

Ketorolac Nasal spray-

• Adults weighing 50 kg or more: 31.5 mg or 2 spray in each nostril every 6 to 8 hours. Your doctor may adjust your dose if needed. However, the dose is not more than 126 mg (a total of 8 sprays) per day.
• Older adults and adults weighing less than 50 kg:15.75 mg or 1 spray in only one nostril every 6 to 8 hours. However, the dose is usually not more than 63 mg (a total of 4 sprays) per day.
• Children: Use and dose must be determined by your doctor.

Ofloxacin Eye: Instill 1 drop in the affected eye(s) every 2 to 4 hours for the first two days and then 4 times daily. The length of treatment should not exceed ten days.

Ofloxacin Ear: Instill 1-2 drops in the affected ear(s) twice daily or as needed.

Ofloxacin Intravenous (Adult):

• Skin and soft tissue infections: 400 mg bid infused over at least 1 hr.
• Complicated urinary tract infections: 200 mg daily by infusion over at least 30 min. Max: 400 mg bid infused over at least 1 hr.
• Lower respiratory tract infections, Septicaemia: 200 mg bid by infusion over at least 30 min. Max: 400 mg bid infused over at least 1 hr.

Ofloxacin Oral (Adult):

General dosage recommendations: The dose of ofloxacin is determined by the type and severity of the infection. The dosage range for adults is 200 mg to 800 mg daily. Up to 400 mg may be given as a single dose, preferably in the morning, larger doses should be given as two divided doses. Ofloxacin tablets should be swallowed with liquid; they should not be taken within two hours of intake of magnesium/aluminium containing antacids or iron preparations since reduction of absorption of ofloxacin can occur.

• Enteric fever: For adults 200 mg, every 12 hours, for 5 days. For children 15 mg/kg/day in 2 divided doses for 3 days.
• Shigellosis: 400 mg single dose.
• Multi-drug-resistant tuberculosis: 400 mg twice daily along with conventional anti-tuberculosis drugs.
• Lower respiratory tract infection: 400 mg daily, increasing, if necessary, to 400 mg twice daily.
• Uncomplicated Urinary Tract Infections: A single dose of 200/400 mg.
• Uncomplicated urethral and cervical gonorrhoea: A single dose of 400 mg.
• Non-gonococcal urethral and cervicitis: 400 mg daily in single or divided doses.
• Complicated Urinary Tract Infection: 200/400 mg/day for 7 days.

Children: Ofloxacin is usually not indicated for use in children or growing adolescents.

Elderly: No adjustment of dosage is required in the elderly.

May be taken with or without food. Avoid antacids or supplements containing Fe or Zn within 2 hr before or after ofloxacin. Ensure adequate hydration.

Side Effects

Commonly occurring side-effects are nausea, vomiting, gastro intestinal bleeding,melaena, peptic ulcer, pancreatitis, anxiety, drowsiness, dizziness, headache, hallucinations,excessive thirst, inability to concentrate, insomnia, malaise, fatigue, pruritus, urticaria, skin photosensitivity, Lyell's syndrome, Stevens-Johnson syndrome, flushing, bradycardia, hypertension, palpitations, chest pain, infertility in female, dyspnoea, asthma, pulmonary oedema, fever, injection site pain.

Ofloxacin Eye: Transient ocular irritation, burning, stinging, redness, itching or photophobia have been reported.

Ofloxacin Ear: Mild irritation or mild discomfort in the ear may occur. Symptoms of an allergic reaction include rash, itching, swelling or trouble breathing.

Ofloxacin tablet or injection is generally well tolerated and clinical side-effects of ofloxacin has been quite low. Among the adverse effects gastrointestinal and central nervous systems' reactions are common. Nausea, rash, vomiting, abdominal pain, diarrhoea and gastrointestinal distress are the gastrointestinal adverse effects. Common central nervous system reactions are headache, dizziness and insomnia.

Toxicity

The rate of adverse effects increases with higher doses of ketorolac. The most frequently observed adverse effects in patients occurring with an incidence of greater than 10% include: abdominal pain, dyspepsia, nausea, and headaches. Most adverse effects associated with short term use are mild in nature, related to the gastrointestinal tract and nervous system, and occur in roughly 39% of patients. Common symptoms of ketorolac overdose include nausea, vomiting, epigastric pain, gastrointestinal bleeding, lethargy and drowsiness. More rare symptoms of overdose include acute renal failure, hypertension, respiratory depression, and coma.

Ketorolac is classified as Pregnancy Category C since there is a lack of evidence demonstrating safety in pregnant women. NSAIDs including ketorolac increase the risk of premature closure of the fetal ductus arteriosus in the 3rd trimester; therefore, beginning at 30 weeks gestation, pregnant women should avoid ketorolac.

Ketorolac has been shown to be excreted in breast milk, and although available data has not demonstrated any adverse effects in nursing infants, practitioners should proceed with caution when suggesting ketorolac for nursing mothers. The benefits should outweigh the risks and the mother should be counselled to monitor the infant closely and to contact the infant's healthcare provider should any adverse effects arise.

Women who are trying to conceive are not advised to take ketorolac since it's effect on prostaglandin synthesis may impair fertility.

LD₅₀=5450 mg/kg (orally in mice)

Precaution

Patients over the age of 65 years may be at a greater risk of experiencing adverse events than younger patients. Ketorolac tromethamine can cause gastro-intestinal irritation, ulcers or bleeding in patients with or without a history of previous symptoms. Bronchospasm may be precipitated in patients with a history of asthma. Since ketorolac tromethamine and its metabolites are excreted primarily by the kidney, patients with moderate to severe impairment of renal function (serum creatinine greater than 160 micromol/l) should not receive. Fluid retention and oedema have been reported with the use of Ketorolac tromethamine.

Patients being treated with Ofloxacin should not expose themselves unnecessarily to strong sunlight and should avoid UV rays. Caution is recommended if the drug is to be used in psychotic patients or in-patients with a history of psychiatric disease.

Prolonged use of eye drops & ear drops may result in overgrowth of non-susceptible organisms and secondary infection respectively.

Interaction

Ketorolac tromethamine should not be used with other NSAIDs or in patients receiving aspirin because of the potential for additive side effects. Care should be taken when administering Ketorolac tromethamine with anti-coag ulants since co-administration may cause an enhanced anti-coagulant effect. Ketorolac tromethamine and other non-steroidal anti-inflammatory drugs can reduce the anti hypertensive effect of beta-blockers and may increase the risk of renal impairment when administered concurrently with ACE inhibitors, particularly in volume depleted patients. Caution is advised when methotrexate is administered concurrently, since some prostaglandin synthesis inhibiting drugs have been reported to reduce the clearance of methotrexate, and thus possibly enhance its toxicity. Probenecid should not be administered concurrently with ketorolac tromethamine because of increases in ketorolac plasma level and half-life.

Antacids containing magnesium, aluminium or calcium may decrease absorption of ofloxacin. Iron or Zinc may decrease oral absorption of ofloxacin.

Volume of Distribution

The apparent volume of distribution of ketorolac in healthy human subjects is 0.25 L/kg or less.

Elimination Route

Ketorolac is rapidly, and completely absorbed after oral administration with a bioavailability of 80% after oral administration. Cmax is attained 20-60 minutes after administration, and after intramuscular administration, the area under the plasma concentration-time curve (AUC) is proportional to the dose administered.

After intramuscular administration, ketorolac demonstrates a time to maximal plasma concentration (tmax) of approximately 45-50 minutes, and a tmax of 30-40 minutes after oral administration. The rate of absorption may be reduced by food; however, the extent of absorption remains unaffected.

Bioavailability of ofloxacin in the tablet formulation is approximately 98%

Half Life

Ketorolac tromethamine is administered as a racemic mixture, therefore the half-life of each enantiomer must be considered. The half life of the S-enantiomer is ~2.5 hours, while the half life of the R-enantiomer is ~5 hours. Based on this data, the S enantiomer is cleared about twice as fast as the R enantiomer.

9 hours

Clearance

The plasma clearance of ketorolac is 0.021 to 0.037 L/h/kg. Further, studies have illustrated that clearance of oral, IM and IV doses of ketorolac are comparable which suggests linear kinetics. It should also be noted that clearance in children is about double the clearance found in adults.

Elimination Route

Ketorolac is primarily renally eliminated and approximately 92% of the dose can be recovered in the urine with 60% of this proportion recovered unchanged, and 40% recovered as metabolites. In addition 6% of a single dose is eliminated in the feces.

Ofloxacin is mainly eliminated by renal excretion, where between 65% and 80% of an administered oral dose of ofloxacin is excreted unchanged via urine within 48 hours of dosing. About 4-8% of an ofloxacin dose is excreted in the feces and the drug is minimally subject to biliary excretion.

Pregnancy & Breastfeeding use

Safety in human pregnancy has not been established. Ketorolac has been detected in human milk at low levels. Ketorolac is therefore contraindicated during pregnancy, labour or delivery, or in mothers who are breast feeding.

Use in pregnancy: There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in lactation: It is not known whether Ofloxacin is excreted in human milk. Cautions should be taken when Ofloxacin eye & ear drops is administered during lactation.

Contraindication

Ketorolac Tromethamine is contraindicated in patients with known hypersensitivity to NSAIDs and any of the components of Ketorolac Tromethamine. Moreover, the patient with the history of asthma, nasal polyp, angioedema, peptic ulcer and bleeding, bleeding disorders are contraindicated for this drug.

It is contraindicated in patients who are hypersensitive to Ofloxacin or any other component of Ofloxacin (Eye/Ear Drops).

Ofloxacin tablet injection should not be used in-patients with known hypersensitivity to 4-fluoroquinolone antibacterials. It is contraindicated in-patients with a history of epilepsy or with a lowered seizure threshold. Ofloxacin is usually contraindicated in children or growing adolescents and in pregnant or breast feeding women.

Special Warning

Renal Impairment:

• CrCl <20 and patients on haemodialysis or peritoneal dialysis: 100 mg 24 hrly following usual initial dose.
• CrCl 20-50: Reduce dose by half 24 hrly following usual initial dose.

Hepatic Impairment:Severe: Reduce dose. Max: 400 mg daily

Acute Overdose

Symptoms: Abdominal pain, nausea, vomiting, hyperventilation, peptic ulceration, erosive gastritis and renal dysfunction.

Management: Symptomatic and supportive treatment. Consider gastric lavage or admin of activated charcoal within 1 hr of ingestion.

Symptoms: Confusion, dizziness, impairment of consciousness, convulsive seizures, GI reactions (e.g. nausea, mucosal erosions).

Management: Symptomatic and supportive treatment. Remove any unabsorbed drug by gastric lavage or admin of adsorbants and Na sulfate. Antacids are recommended for protection of gastric mucosa. Elimination may be increased by forced diuresis.

Storage Condition

Tablet & injection should be store in a cool & dry place, protect from light & moisture.

Store between 15-30° C. Protect from light.

Innovators Monograph

You find simplified version here Ofel Plus