Actions of Etolor in details
Similar to other NSAIDs, the anti-inflammatory effects of Etolor result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etolor binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etolor 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.
How should I take Etolor?
For safe and effective use of Etolor, do not take more of it, do not take it more often, and do not take it for a longer time than ordered by your doctor. Taking too much of Etolor may increase the chance of unwanted effects, especially in elderly patients.
When used for severe or continuing arthritis, Etolor must be taken regularly as ordered by your doctor in order for it to help you. Etolor usually begins to work within one week, but in severe cases up to two weeks or even longer may pass before you begin to feel better. Also, several weeks may pass before you feel the full effects of Etolor.
Swallow the extended-release tablet whole. Do not crush, break, or chew it.
Dosing
The dose of Etolor will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Etolor. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For acute pain:
- For oral dosage form (capsules or tablets):
- Adults—200 to 400 milligrams (mg) every 6 to 8 hours. However, the dose usually is not more than 1000 mg per day.
- Children—Use and dose must be determined by your doctor.
- For oral dosage form (capsules or tablets):
- For osteoarthritis and rheumatoid arthritis:
- For oral dosage form (capsules or tablets):
- Adults—300 mg two or three times a day, or 400 or 500 mg two times a day. If you will be taking Etolor for a long time, your doctor may lower your dose to 600 mg once a day. The dose usually is not more than 1000 mg per day.
- Children—Use and dose must be determined by your doctor.
- For oral dosage form (extended-release tablets):
- Adults—400 mg to 1000 mg once a day.
- Children 6 to 16 years of age—Dose is based on body weight and must be determined by your doctor.
- Children below 6 years of age—Use and dose must be determined by your doctor.
- For oral dosage form (capsules or tablets):
Missed Dose
If you miss a dose of Etolor, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Etolor administration
Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.
Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.
It may take up to 2 weeks of using this medicine before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve.
If you take Etolor for a long period of time, your doctor may want to check you on a regular basis to make sure this medication is not causing harmful effects. Do not miss any scheduled visits to your doctor.
This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using Etolor.
Store Etolor at room temperature away from moisture and heat.
Etolor pharmacology
Pharmacodynamics
Etolor Extended-Release Tablets are a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of Etolor Extended-Release Tablets, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin synthetase inhibition.
Pharmacokinetics
AbsorptionEtolor Extended-Release Tablets and Etolor tablets both contain Etolor, but differ in their release characteristics. The systemic availability of Etolor from Etolor Extended-Release Tablets is generally greater than 80%. Etolor does not undergo significant first-pass metabolism following oral administration. After oral administration of Etolor Extended-Release Tablets in doses up to 800 mg once daily, peak concentrations occur approximately 6 hours after dosing and are dose proportional for both total and free Etolor.
Table 1 shows the comparison of Etolor pharmacokinetic parameters after the administration of Etolor tablets and Etolor Extended-Release Tablets.
Table 2 shows the Etolor pharmacokinetic parameters in various populations. The data from patients with renal and hepatic impairment were obtained following administration of (immediate-release) Etolor tablets.
| Mean (CV)%* | ||
|---|---|---|
| Pharmacokinetic Parameters | Etolor Tablets | Etolor Extended-Release Tablets |
| ||
Extent ofOral Absorption (Bioavailability) [F] | ≥ 80% | ≥ 80% |
| Time to Peak Concentration (Tmax), h | 1.4 (61%) | 6.7 (47%) |
Oral Clearance (CL/F), mL/h/kg | 49.1 (33%) | 46.8 (37%) |
| Apparent Volume of Distribution (Vd/F), mL/kg | 393 (29%) | 566 (26%) |
| Terminal Half-Life (t½), h | 6.4 (22%) | 8.4 (30%) |
| Etolor Extended-Release Tablets | Etolor Tablets | |||||||
|---|---|---|---|---|---|---|---|---|
| PK Parameters | Normal Healthy Adults (18 to 44)† (n=116) | Healthy Males (18 to 43) (n=102) | Healthy Females (25 to 44) (n=14) | Elderly (>65 yr) (66 to 88) (n=24) | Hemodialysis‡ (24 to 65) (n=9) | Renal Impairment‡ (46 to 73) (n=10) | Hepatic Impairment‡(34 to 60) (n=9) | |
| Dialysis On | Dialysis Off | |||||||
| NA = not available | ||||||||
| ||||||||
| Tmax, h | 6.7 (47%)* | 6.8 (45%) | 4.5 (56%) | 6.2 (51%) | 1.7 (88%) | 0.9 (67%) | 2.1 (46%) | 1.1 (15%) |
Oral Clearance, mL/h/kg (CL/F) | 46.8 (37%) | 46.8 (37%) | 47.2 (38%) | 51.6 (40%) | NA | NA | 58.3 (19%) | 42.0 (43%) |
| Apparent Volume of Distribution, mL/kg (Vd/F) | 566 (26%) | 580 (26%) | 459 (28%) | 552 (34%) | NA | NA | NA | NA |
| Terminal Half-Life, h | 8.4 (30%) | 8.4 (29%) | 7.6 (45%) | 7.8 (26%) | 5.1 (22%) | 7.5 (34%) | NA | 5.7 (24%) |
Food has no significant effect on the extent of Etolor Extended-Release Tablets absorption, however, food significantly increased Cmax (54%) following a 600 mg dose.
The extent of absorption of Etolor is not affected when Etolor is administered with antacid. Coadministration, with an antacid, decreases the peak concentration reached by about 15 to 20% with no measurable effect on time-to-peak.
Distribution
The mean apparent volume of distribution (Vd/F) of Etolor following administration of Etolor Extended-Release Tablets is 566 mL/kg. Etolor is more than 99% bound to plasma proteins, primarily to albumin, and is independent of Etolor concentration over the dose range studied. It is not known whether Etolor is excreted in human milk. However, based on its physical-chemical properties, excretion into breast milk is expected.
Metabolism
Etolor metabolites do not contribute significantly to the pharmacological activity of Etolor Extended-Release Tablets.
Following administration of immediate-release Etolor, several metabolites have been identified in human plasma and urine. Other metabolites remain to be identified. The metabolites include 6-, 7-, and 8- hydroxylated Etolor and Etolor glucuronide. After a single dose of 14C-Etolor, hydroxylated metabolites accounted for less than 10% of total drug in serum. On chronic dosing, hydroxylated-Etolor metabolites do not accumulate in the plasma of patients with normal renal function. The extent of accumulation of hydroxylated-Etolor metabolites in patients with renal dysfunction has not been studied. The role, if any, of a specific cytochrome P450 system in the metabolism of Etolor is unknown. The hydroxylated-Etolor metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces.
Excretion
The mean oral clearance of Etolor following oral Etolor Extended-Release Tablets dosing is 47 (±17) mL/h/kg. The terminal half-life (t½) of Etolor after Etolor Extended-Release Tablets administration is 8.4 hours compared to 6.4 hours for Etolor tablets. Approximately 1% of an Etolor tablet dose is excreted unchanged in the urine, with 72% of the dose excreted into the urine as parent drug plus metabolites:
| -Etolor, unchanged | 1% |
| -Etolor glucuronide | 13% |
| -hydroxylated metabolites (6-, 7-, and 8-OH) | 5% |
| -hydroxylated metabolite glucuronides | 20% |
| -unidentified metabolites | 33% |
Fecal excretion accounted for 16% of the dose.
Special Populations
Geriatric
In clinical studies, age was not shown to have any effect on half-life or protein binding, and demonstrated no change in expected drug accumulation. No dosage adjustment is generally necessary in the elderly on the basis of pharmacokinetics. The elderly may need dosage adjustment, however, as they may be more sensitive to antiprostaglandin effects than younger patients.
Pediatric
The pharmacokinetics of Etolor Extended-Release Tablets were assessed in an open-label, 12-week clinical trial which included plasma sampling for population pharmacokinetics. Seventy-two (72) patients, 6 to 16 years of age, with juvenile rheumatoid arthritis, received Etolor Extended-Release Tablets in doses of 13.3 to 21.3 mg/kg given as 400 to 1000 mg once daily. The results from a population pharmacokinetic analysis based on the 59 subjects who completed the trial are as follows:
| Parameter | JRA* (Age: 6 to 16)† n = 59 |
|---|---|
| |
Oral Clearance (CL/F), mL/h/kg | 47.8 (38%) |
| Apparent Volume of Distribution (Vd/F), mL/kg | 78.9 (61%) |
| Half-life (t½), h | 12.1 (75%) |
While similar, the pharmacokinetic parameters for children with juvenile rheumatoid arthritis did not directly correlate with adult pharmacokinetic data in rheumatoid arthritis. In the population pharmacokinetic analysis, body weights below 50 kg were found to correlate with CL/F.
Race
Pharmacokinetic differences due to race have not been identified. Clinical studies included patients of many races, all of whom responded in a similar fashion.
Hepatic Insufficiency
The pharmacokinetics of Etolor following administration of Etolor Extended-Release Tablets have not been investigated in subjects with hepatic insufficiency. Following administration of Etolor tablets, the plasma protein binding and disposition of total and free Etolor were unchanged in the presence of compensated hepatic cirrhosis. Although no dosage adjustment is generally required in patients with chronic hepatic diseases, Etolor clearance is dependent on liver function and could be reduced in patients with severe hepatic failure.
Renal Insufficiency
The pharmacokinetics of Etolor following administration of Etolor Extended-Release Tablets have not been investigated in subjects with renal insufficiency. Etolor renal clearance following administration of Etolor tablets was unchanged in the presence of mild-to-moderate renal failure (creatinine clearance, 37 to 88 mL/min). Although renal elimination is a significant pathway of excretion for Etolor metabolites, no dosing adjustment in patients with mild-to-moderate renal dysfunction is generally necessary. Etolor plasma protein binding decreases in patients with severe renal deficiency. Etolor should be used with caution in such patients because, as with other NSAIDs, it may further decrease renal function in some patients. Etolor is not significantly removed from the blood in patients undergoing hemodialysis.
References
- DailyMed. "ETODOLAC: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- EPA DSStox. "Etodolac: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Etolor are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Etolor. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
