Ketsol Plus Eye

Ketsol Plus Eye Uses, Dosage, Side Effects, Food Interaction and all others data.

Chlorpheniramine is an alkylamine antihistamine. It is one of the most potent H1 blocking agents and is generally effective in relatively low doses. Chlorpheniramine is not so prone to produce drowsiness, readily absorbed from the gastro-intestinal tract, metabolised in the liver and excreted usually mainly as metabolised in the urine.

In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) chemically related to indomethacin and tolmetin. Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the S-form having analgesic activity. Its antiinflammatory effects are believed to be due to inhibition of both cylooxygenase-1 (COX-1) and cylooxygenase-2 (COX-2) which leads to the inhibition of prostaglandin synthesis leading to decreased formation of precursors of prostaglandins and thromboxanes from arachidonic acid. The resultant reduction in prostaglandin synthesis and activity may be at least partially responsible for many of the adverse, as well as the therapeutic, effects of these medications. Analgesia is probably produced via a peripheral action in which blockade of pain impulse generation results from decreased prostaglandin activity. However, inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation may also contribute to the analgesic effect. In terms of the ophthalmic applications of ketorolac - ocular administration of ketorolac reduces prostaglandin E2 levels in aqueous humor, secondary to inhibition of prostaglandin biosynthesis.

Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever.

As a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme. Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations.

Phenylephrine is an alpha-1 adrenergic receptor agonist used to treat hypotension, dilate the pupil, and induce local vasoconstriction. The action of phenylephrine, or neo-synephrine, was first described in literature in the 1930s.

Phenylephrine was granted FDA approval in 1939.

Phenylephrine is an alpha-1 adrenergic agonist that raises blood pressure, dilates the pupils, and causes local vasoconstriction. Ophthalmic formulations of phenylephrine act for 3-8 hours while intravenous solutions have an effective half life of 5 minutes and an elimination half life of 2.5 hours. Patients taking ophthalmic formulations of phenylephrine should be counselled about the risk of arrhythmia, hypertension, and rebound miosis. Patients taking an intravenous formulation should be counselled regarding the risk of bradycardia, allergic reactions, extravasation causing necrosis or tissue sloughing, and the concomitant use of oxytocic drugs.

Ketsol Plus Eye
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Ketsol Plus Eye
Generic	Ketorolac + Phenylephrine + Chlorpheniramine
Weight	0.5%w/v
Type	Drops
Therapeutic Class
Manufacturer	Kaizen Pharmaceuticals Pvt Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Indicated mainly in allergic conditions including urticaria, sensitivity reactions, angioneurotic oedema, seasonal hay fever, vasomotor rhinitis, cough, common cold, motion sickness.

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

Phenylephrine is an alpha-1 adrenergic agonist used in the management of hypotension, generally in the surgical setting associated with the use of anesthetics.

Phenylephrine injections are indicated to treat hypotension caused by shock or anesthesia, an ophthalmic formulation is indicated to dilate pupils and induce vasoconstriction, an intranasal formulation is used to treat congestion, and a topical formulation is used to treat hemorrhoids. Off-label uses include situations that require local blood flow restriction such as the treatment of priapism.

Ketsol Plus Eye is also used to associated treatment for these conditions: Allergic Contact Dermatitis, Allergic Reaction, Allergic Rhinitis (AR), Allergic cough, Allergies, Allergies caused by Serum, Allergy to House Dust, Allergy to vaccine, Angioneurotic Edema, Asthma, Bronchial Asthma, Bronchitis, Common Cold, Conjunctival congestion, Conjunctivitis, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Coughing caused by Flu caused by Influenza, Drug Allergy, Eye allergy, Fever, Flu caused by Influenza, Food Allergy, Headache, Headache caused by Allergies, Itching of the nose, Itching of the throat, Migraine, Nasal Congestion, Nasal Congestion caused by Common Cold, Pollen Allergy, Productive cough, Pruritus, Rash, Rhinorrhoea, Seasonal Allergic Conjunctivitis, Sinus Congestion, Sinusitis, Sneezing, Transfusion Reactions, Upper Respiratory Tract Infection, Upper respiratory tract hypersensitivity reaction, site unspecified, Urticaria, Vasomotor Rhinitis, Acute Rhinitis, Allergic purpura, Conjunctival hyperemia, Dry cough, Excess mucus or phlegm, Itchy throat, Mild bacterial upper respiratory tract infections, Ocular hyperemia, Throat inflammation, Upper airway congestion, Upper respiratory symptoms, Watery eyes, Watery itchy eyes, Airway secretion clearance therapyAcute 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 painAllergic Rhinitis (AR), Anorectal discomfort, Cold, Common Cold, Common Cold/Flu, Congestion of the Conjunctivas, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Eye allergy, Eye redness, Fever, Flu caused by Influenza, Headache, Headache caused by Allergies, Headache caused by Common Cold, Headache caused by Pollen Allergy, Hemorrhoids, Hypotension, Irritative cough, Itching of the nose, Itching of the throat, Laryngotracheitis, Nasal Congestion, Nose discomfort, Ocular Inflammation, Ocular Irritation, Paroxysmal Supraventricular Tachycardia, Pollen Allergy, Respiratory tract congestion, Respiratory tract irritation, Rhinopharyngitis, Rhinorrhoea, Seasonal Allergies, Shock, Cardiogenic, Sinus Congestion, Sinus pressure, Sinusitis, Sneezing, Sore Throat, Tracheobronchitis, Upper respiratory tract hypersensitivity reaction, site unspecified, Vasomotor Rhinitis, Aching caused by Flu caused by Influenza, Bronchial congestion, Itchy throat, Minor aches and pains, Watery itchy eyes, Airway secretion clearance therapy, Antihistamine, Dilatation of the pupil, Vasoconstrictor in regional analgesia therapy

How Ketsol Plus Eye works

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

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.

Phenylephrine is an alpha-1 adrenergic agonist that mediates vasoconstriction and mydriasis depending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha-1 adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance. Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia.

Dosage

Ketsol Plus Eye dosage

Adults: 4 mg 3-4 times daily.

Children:

Up to 1( one) year: 1 mg twice daily
1-5 years: 1 mg 3-4 times daily
6-12 years: 2 mg 3-4 times daily or as directed by the physician

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.

Side Effects

Drowsiness, dizziness, headache, psychomotor impairment, urinary retention, dry mouth, blurred vision and gastro intestinal disturbances, paradoxical stimulation may rarely occur, especially in high dosage or in children.

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.

Toxicity

Oral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.

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.

Patients experiencing and overdose may present with headache, hypertension, reflex bradycardia, tingling limbs, cardiac arrhythmias, and a feeling of fullness in the head. Overdose may be treated by supportive care and discontinuing phenylephrine, chronotropic medications, and vasodilators. Subcutaneous phentolamine may be used to treat tissue extravasation.

Precaution

Chlorpheniramine may produce mild sedation and it is advised that patients under continuous treatment should avoid operating machinery. Not recommended during pregnancy & lactation.

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.

Interaction

Alcohol, CNS depressants, anticholinergic drugs, MAOIs.

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.

Volume of Distribution

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

The volume of distribution of phenylephrine is 340L.

Elimination Route

Well absorbed in the gastrointestinal tract.

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.

Phenylephrine is 38% orally bioavailable. Clinically significant systemic absorption of ophthalmic formulations is possible, especially at higher strengths and when the cornea is damaged.

Half Life

21-27 hours

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.

Intravenous phenylephrine has an effective half life of 5 minutes and an elimination half life of 2.5 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.

Phenylephrine has an average clearance of 2100mL/min.

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.

86% of a dose of phenylephrine is recovered in the urine with 16% as the unmetabolized drug, 57% as the inactive meta-hydroxymendelic acid, and 8% as inactive sulfate conjugates.

Pregnancy & Breastfeeding use

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

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.

Contraindication

There is no definite contraindication to therapy. It should be used with caution in epilepsy, prostatic hypertrophy, glaucoma and hepatic disease. The ability to drive or operate machinery may be impaired.

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.