Etokul

Uses

Carefully consider the potential benefits and risks of etodolac capsules and other treatment options before deciding to use etodolac capsules. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.Etodolac are used:1. For acute and long-term use in the management of signs and symptoms of the following:

• Osteoarthritis
• Rheumatoid arthritis

2. For the management of acute pain

Paracetamol IV is used for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, the reduction of fever.

Paracetamol is a non-salicylate antipyretic and non-opioid analgesic agent. Paracetamol IV injection is a sterile, clear, colorless, non pyrogenic, isotonic formulation of Paracetamol intended for intravenous infusion.

Etokul is also used to associated treatment for these conditions: Chronic Back Pain, Extra-Articular Rheumatism, Juvenile Idiopathic Arthritis (JIA), Muscle Spasms, Nonspecific Pain Post Traumatic Injury, Osteoarthritis (OA), Pain, Acute, Postoperative pain, Rheumatoid Arthritis, Spinal DisordersAcute Gouty Arthritis, Acute Musculoskeletal Pain, Allergies, Ankylosing Spondylitis (AS), Arthritis, Chills, Cold, Cold Symptoms, Common Cold, Common Cold/Flu, Cough, Cough caused by Common Cold, Coughing caused by Flu caused by Influenza, Dyskinesia of the Biliary Tract, Dyskinesia of the Urinary Tract, Febrile Convulsions, Febrile Illness Acute, Fever, Fibromyalgia Syndrome, Flu caused by Influenza, Headache, Joint dislocations, Menstrual Distress (Dysmenorrhea), Mild pain, Muscle Inflammation, Muscle Injuries, Muscle Spasms, Musculoskeletal Pain, Nasal Congestion, Neuralgia, Osteoarthritis (OA), Pain, Pollen Allergy, Postoperative pain, Premenstrual cramps, Rheumatoid Arthritis, Rhinopharyngitis, Rhinorrhoea, Severe Pain, Sinusitis, Soreness, Muscle, Spasms, Spastic Pain of the Gastrointestinal Tract, Sprains, Tension Headache, Toothache, Upper Respiratory Tract Infection, Whiplash Syndrome, Acute Torticollis, Mild to moderate pain, Minor aches and pains, Minor pain, Moderate Pain, Airway secretion clearance therapy, Antispasmodic, Bronchodilation

How Etokul works

Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.

Dosage

Etokul dosage

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

After observing the response to initial therapy with Etodolac capsules, the dose and frequency should be adjusted to suit an individual patient's needs.

Dosage adjustment of Etodolac is generally not required in patients with mild to moderate renal impairment. Etodolac should be used with caution in such patients, because, as with otherNSAIDs, they may further decrease renal function in some patients with impaired renal function.

Analgesia: The recommended total daily dose of Etodolac for acute pain is up to 1000 mg, given as 200 to 400 mg every 6 to 8 hours. Doses of Etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled clinical trials.

Osteoarthritis and Rheumatoid Arthritis: The recommended starting dose is 300 mg b.i.d., t.i.d., or 400 mg b.i.d., or 500 mgb.i.d.A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aware that doses above 1000 mg/day have not been adequately evaluated in well-controlled clinical trials.

In chronic conditions, a therapeutic response to therapy with Etodolac is sometimes seen within one week of therapy, but most often is observed by two weeks. After a satisfactory response has been achieved, the patient's dose should be reviewed and adjusted as required.

Adults and adolescents weighing 50 kg and over: the recommended dosage of Paracetamol IV is 1000 mg every 6 hours or 650 mg every 4 hours, with a maximum single dose of Paracetamol IV of 1000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 4000 mg per day.

Adults and adolescents weighing under 50 kg: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.

Children >2 to 12 years of age: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.

Side Effects

The common side effects of Etodolac involve the gastrointestinal system. It can cause abdominal pain, constipation, diarrhea, dyspepsia, flatulence, heartburn, nausea, GI ulcers, vomiting. Other events including abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus etc.

As all paracetamol products, adverse drug reactions are rare (>1/10000, <1/1000) or very rare (<1/10000). Frequent adverse reactions at injection site have been reported during clinical trials (pain and burning sensation). Very rare cases of hypersensitivity reactions ranging from simple skin rash or urticaria to anaphylactic shock have been reported and require discontinuation of treatment. Cases of erythema, flushing, pruritus and tachycardia have been reported.

Toxicity

Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of etodolac. Etodolac may increase blood pressure and/or cause fluid retention and edema. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Common adverse events include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anemia, dizziness, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.

Precaution

Etodolac should be given with caution in patients with severe hepatic reactions, pre-existing asthma, fluid retention, hypertension or heart failure. If clinical sings and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash etc.), it should be discontinued.

Administration of Paracetamol in doses higher than recommended may result in hepatic injury, including the risk of severe hepatotoxicity and death. Do not exceed the maximum recommended daily dose of Paracetamol. Use caution when administering Paracetamol in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss), or severe renal impairment (creatinine clearance < 30 ml/min). There were infrequent reports of life-threatening anaphylaxis requiring emergent medical attention. Discontinue Paracetamol IV immediately if symptoms associated with allergy or hypersensitivity occurs. Do not use Paracetamol IV in patients with Paracetamol allergy.

Interaction

Since Etodolac is extensively protein-bound, it may be necessary to modify the dosage of other highly protein-bound drugs. The concomitant administration of Warfarin and Etodolac should not require a dosage adjustment of either drug, however it has rarely led to prolonged prothrombin times, therefore caution should be exercised when Etodolac is administered with Warfarin. Concomitant use of Ciclosporin, Methotrexate, Digoxin, or Lithium with NSAIDs may cause an increase in serum levels of these compounds and associated toxicities. Care should also be taken in patients treated with any of the following drugs as interactions have been reported in some patients: Anti-hypertensives, Mifepristone, other Analgesics, Corticosteroids and Quinolone Antibiotics.

Volume of Distribution

• 390 mL/kg

Volume of distribution is about 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Acetaminophen appears to be widely distributed throughout most body tissues except in fat.

Elimination Route

Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%.

Half Life

Terminal t_1/2, 7.3 ± 4.0 hours. Distribution t_1/2, 0.71 ± 0.50 hours

The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg. After an overdose, the half-life can range from 4 to 8 hours depending on the severity of injury to the liver, as it heavily metabolizes acetaminophen.

Clearance

• Oral cl=49.1 mL/h/kg [Normal healthy adults]
• Oral cl=49.4 mL/h/kg [Healthy males (18-65 years)]
• Oral cl=35.7 mL/h/kg [Healthy females (27-65 years)]
• Oral cl=45.7 mL/h/kg [Eldery (>65 years)]
• Oral cl=58.3 mL/h/kg [Renal impairement (46-73 years)]
• Oral cl=42.0 mL/h/kg [Hepatic impairement (34-60 years)]

Adults: 0.27 L/h/kg following a 15 mg/kg intravenous (IV) dose. Children: 0.34 L/h/kg following a 15 mg/kg intravenous (IV dose).

Elimination Route

It is not known whether etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Etodolac is extensively metabolized in the liver. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces (16% of dose). Approximately 1% of a etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite.

Pregnancy & Breastfeeding use

Pregnancy: There are no adequate and well-controlled studies in pregnant women. It should be use in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether Etodolac is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

Pregnancy Category C. There are no studies of intravenous Paracetamol in pregnant women; however, epidemiological data on oral Paracetamol use in pregnant women show no increased risk of major congenital malformations. Animal reproduction studies have not been conducted with IV Paracetamol and it is not known whether Paracetamol IV can cause fetal harm when administered to a pregnant woman. Paracetamol IV should be given to a pregnant woman only if clearly needed. There are no adequate and well-controlled studies with Paracetamol IV during labor and delivery; therefore, it should be used in such settings only after a careful benefit-risk assessment. While studies with Paracetamol IV have not been conducted, Paracetamol is secreted in human milk in small quantities after oral administration.

Contraindication

Etodolac is contraindicated in patients with known hypersensitivity to Etodolac. Etodolac should not be given to patients who have experienced asthma, urticaria or other allergic-type reactions after taking Aspirin or other NSAIDs.

Paracetamol is contraindicated in patients with known hypersensitivity to its active ingredient or to any of the excipients in the intravenous formulation. Also contraindicated in patients with severe hepatic impairment or severe active liver disease

Special Warning

Pediatric Use: The safety and effectiveness of Paracetamol IV for the treatment of acute pain and fever in pediatric patients ages 2 years and older is supported by evidence from adequate and well-controlled studies of Paracetamol IV in adults.

Geriatric use: No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Patients with Hepatic Impairment: Paracetamol is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease. A reduced total daily dose of Paracetamol may be warranted.

Patients with Renal Impairment: In cases of severe renal impairment (creatinine clearance < 30 ml/min), longer dosing intervals and a reduced total daily dose of Paracetamol may be warranted.

Acute Overdose

Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain which are generally reversible with supportive care.

Storage Condition

Store at a cool and dry place protected from light & moisture. Keep out of reach of children.

Store in a cool & dry place & away from children. For single use only. The product should be used within 6 hours after opening. Do not refrigerate or freeze.

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