entrophn.html

[Guest guest]

http://www.rxmed.com/monographs/entrophn.html

ENTROPHEN®

FrosstASANonsteroidal Anti-inflammatory - Analgesic - Platelet Aggregation

Inhibitor

Pharmacology: ASA has analgesic, antipyretic and anti-inflammatory

properties.

In rheumatic diseases, although the analgesic and antipyretic effects are

useful, the major purpose for which ASA is used is to reduce the intensity

of the inflammatory process. Inhibition of prostaglandin synthesis may be

involved in the anti-inflammatory action of ASA.

ASA also alters platelet aggregation and release reaction by inhibiting

prostaglandin synthesis. Thromboxane A2 is an essential step in platelet

aggregation. ASA prevents Thromboxane A2 formation by acetylation of

platelet cyclooxygenase. This inhibition of prostaglandin synthesis is

irreversible and affects platelet function for the life of the platelet.

The enteric-coating substantially resists disintegration in aqueous fluids

having a pH lower than 3.5 for a period of at least 2 hours and is capable

of disintegrating in aqueous fluids having a pH of at least 5.5 in from 10

to 30 minutes. Thus, enteric-coating effectively inhibits the release of ASA

in the stomach, while allowing the tablet to dissolve in the upper portion

of the small intestine for absorption from the duodenal area.

Clinical experience has shown that enteric-coated ASA diminishes or

eliminates gastric distress during long-term treatment with high doses of

ASA.

Pharmacokinetics: Since Entrophen tablets are enteric-coated, the

pharmacological effects are not immediate. Peak serum salicylate

concentrations are reached 6 to 8 hours after single oral administration.

This means that Entrophen tablets are more useful for chronic administration

as in arthritis, than for providing prompt relief of pain and fever.

The plasma half-life of salicylate concentrations is dose-dependent being 3

to 6 hours at low doses (325 mg to 1.3 g) and 15 to 30 hours at high doses.

Indications: Whenever gastric intolerance to ASA is of concern.

For the relief of signs and symptoms of osteoarthritis, rheumatoid

arthritis, spondylitis, bursitis and other forms of rheumatism,

musculoskeletal disorders; also of rheumatic fever, however, penicillin and

other appropriate therapy should be administered concomitantly. ASA is

generally considered to be the primary therapy for most forms of arthritis.

For reducing the risk of recurrent transient ischemic attacks or stroke in

men who have had transient ischemia of the brain due to fibrin platelet

emboli. At present, there is no evidence that ASA is effective in reducing

transient ischemic attacks in women, or is of benefit in the treatment of

completed strokes in men or women.

Contraindications: Sensitivity to the ingredients, active peptic ulcer,

patients who had a bronchospastic reaction to ASA or nonsteroidal

anti-inflammatory drugs.

Warnings: ASA is one of the most frequent causes of accidental poisoning in

toddlers and infants. ASA should, therefore, be kept well out of the reach

of all children.

Precautions: Salicylates should be administered with caution to patients

with asthma and other allergic conditions, with a history of

gastrointestinal ulcerations, with bleeding tendencies, with significant

anemia or with hypoprothrombinemia.

Salicylates can produce changes in thyroid function tests.

Acute hepatitis has been reported rarely in patients with systemic lupus

erythematosus and juvenile rheumatoid arthritis with plasma salicylate

concentrations above 25 mg/100 mL. Patients have recovered upon cessation of

therapy.

Pregnancy: ASA does not appear to have any teratogenic effects. ASA has been

found to delay parturition in rats. This effect has also been described with

nonsteroidal anti-inflammatory agents which inhibit prostaglandin synthesis.

High doses (3 g daily) of ASA during pregnancy may lengthen the gestation

and parturition time.

Because of possible adverse effects on the neonate and the potential for

increased maternal blood loss, ASA should be avoided during the last 3

months of pregnancy.

Children: Recent studies have suggested that ASA usage may cause the

development of Reye's Syndrome in children and teenagers with acute febrile

illnesses, especially influenza and varicella. Although a direct causal

relationship has not been established, it is recommended that salicylates be

avoided when possible, in children and teenagers with influenza or

varicella.

Drug Interactions: Caution is necessary when ASA and anticoagulants are

prescribed concurrently, as ASA may potentiate the action of anticoagulants.

Salicylates may potentiate sulfonylurea hypoglycemic agents. Large doses of

salicylates may have a hypoglycemic action, and thus, affect the insulin

requirements of diabetics.

Although salicylates in large doses are uricosuric agents, smaller amounts

may depress uric acid clearance, and thus, decrease the uricosuric effects

of probenecid, sulfinpyrazone and phenylbutazone.

Sodium excretion produced by spironolactone may be decreased in the presence

of salicylates.

Salicylates also retard the renal elimination of methotrexate.

Adverse Effects: Gastrointestinal: nausea, vomiting, diarrhea,

gastrointestinal bleeding and/or ulceration.

Ear: tinnitus, vertigo, hearing loss.

Hematologic: leukopenia, thrombocytopenia, purpura.

Dermatologic and Hypersensitivity: urticaria, angioedema, pruritus, various

skin eruptions, asthma and anaphylaxis.

Miscellaneous: acute reversible hepatotoxicity; mental confusion,

drowsiness, sweating and thirst.

Overdose: Symptoms: In mild overdosage, these may include rapid and deep

breathing, nausea, vomiting (leading to alkalosis), hyperpnea, vertigo,

tinnitus, flushing, sweating, thirst and tachycardia. (High blood levels of

ASA lead to acidosis.) Severe cases may show fever, hemorrhage, excitement,

confusion, convulsions or coma and respiratory failure.

Treatment: Treatment is essentially symptomatic and supportive. Administer

water, universal antidote and remove by gastric lavage or emesis. Force

fluids (e.g., salty broth) to replace sodium loss. If the patient is unable

to retain fluids orally, the alkalosis can be treated by hypertonic saline

i.v. If salicylism acidosis is present, sodium bicarbonate i.v. is preferred

because it increases the renal excretion of salicylates. Vitamin K is

indicated if there is evidence of hemorrhage. Hemodialysis has been used

with success.

Respiratory depression may require artificial ventilation with oxygen.

Convulsions may best be treated by the administration of succinylcholine and

artificial ventilation with oxygen. CNS depressant agents should not be

used.

Hyperthermia and dehydration are immediate threats to life and initial

therapy must be directed to their correction and to the maintenance of

adequate renal function. External cooling with cool water or alcohol should

be provided quickly to any child who has a rectal temperature over 40°C.

Dosage: Analgesic/Antipyretic: Patients should be advised not to exceed 4 g

daily. Single doses should not be administered more frequently than every 4

hours.

Adults: Single dose should not exceed 650 mg, to be repeated every 4 to 6

hours; the total daily dosage should not exceed 4 000 mg ASA unless

otherwise advised by a physician, i.e., 12 tablets 325 mg, or 8 tablets 500

mg, or 6 tablets 650 mg, or 4 tablets 975 mg. If the underlying condition

requires continued use of ASA for more than 5 days, a physician should be

consulted.

Children: Only as directed by a physician.

Anti-inflammatory: Because the suppression of inflammation increases with

the dose of salicylate even beyond the point of toxicity, the therapeutic

objective is to employ as large a dose as possible short of toxicity. Most

patients will tolerate blood salicylate levels in the range of 20 to 25 mg%.

The most common reason for failing to obtain a therapeutic response to ASA

is the administration of inadequate doses.

The generally accepted way to achieve effective " anti-inflammatory "

salicylate blood levels of 20 to 25 mg% is to titrate the dosage by starting

with 2.6 to 3.9 g daily, according to the size, age and sex of patient. If

necessary, the dosage is then gradually adjusted by daily increments of 0.65

g. Optimally, salicylate therapy should be monitored by periodic blood

salicylate level determinations. If this is not practical, the appearance of

auditory symptoms in the form of tinnitus or deafness are acceptable as an

indication of the maximum tolerated salicylate dose.

In adults, the median dose at which tinnitus develops is 4.5 g/day, but the

range extends from 2.6 to 6 g/day.

Intermittent administration is ineffective. Patients should be advised not

to vary the dose from day to day depending on the level of pain because that

often fluctuates independently of the intensity of the inflammation. A

continuous regimen of 0.65 g 4 times daily is considered to be minimum

therapy for adults. ASA should be administered 4 times daily. For nighttime

and early morning benefits, the last dose should be given at bedtime.

Once maintenance dose is established, Entrophen 15 Maximum Strength may be

useful to encourage patient compliance.

There is an inverse relation between blood salicylate levels at which

auditory symptoms appear and the age of the patient. In the young adult,

this is usually in the range of 20 to 30 mg%. In children, however, the

level may be much higher, or the effect apparently absent. Because

salicylate toxicity may appear without such warning in children, the usual

practice is to give ASA in a daily dose of 50 to 80 mg/kg of body weight and

to follow blood levels aiming for a concentration of about 30 mg%.

Rheumatic Fever: A total daily dosage of 80 mg/kg of body weight

administered in divided doses to allay the pain, swelling and fever.

Cerebral Ischemic Attacks (Men): The recommended dosage is 1 300 mg/day (650

mg twice a day or 325 mg 4 times a day).

Information for the Patient: See Blue Section - Information for the Patient

" Entrophen " .

Supplied: Regular Strength: Caplets: Each capsule-shaped, yellow,

film-coated caplet, printed ENTROPHEN 325 mg in black on one side, contains:

ASA 325 mg (enteric-coated). Nonmedicinal ingredients: black ferric oxide,

carnauba wax, cellulose acetate phthalate, cornstarch, diethyl phthalate,

guar gum, hydrogenated vegetable oil, hydroxypropyl cellulose, hydroxypropyl

methylcellulose, microcrystalline cellulose, polyvinyl acetate phthalate,

sodium lauryl sulfate, titanium dioxide and yellow ferric oxide. Bottles of

24 (child-resistant package) and 100.

Tablets: Each round, brown, film-coated tablet, printed ENTROPHEN 325 mg in

black on one side, contains: ASA 325 mg (enteric-coated). Nonmedicinal

ingredients: black ferric oxide, cellulose acetate phthalate, cornstarch,

diethyl phthalate, guar gum, hydrogenated vegetable oil, hydroxypropyl

methylcellulose, microcrystalline cellulose, polyvinyl acetate phthalate,

red ferric oxide, sodium lauryl sulfate and sucrose. Bottles of 24

(child-resistant package), 100 and 1 000 (for dispensing use only).

Extra Strength: Tablets: Each oval, pink, film-coated tablet, printed

ENTROPHEN 500 mg in black on one side, contains: ASA 500 mg

(enteric-coated). Nonmedicinal ingredients: allura red aluminum lake, black

ferric oxide, carnauba wax, cellulose acetate phthalate, cornstarch, diethyl

phthalate, guar gum, hydrogenated vegetable oil, hydroxypropyl

methylcellulose, microcrystalline cellulose, sodium lauryl sulfate, sucrose

and titanium dioxide. Bottles of 24 (child-resistant package) and 100.

10 Super Extra Strength: Caplets: Each capsule-shaped orange, film-coated

caplet, printed ENTROPHEN 650 mg in black on one side, contains: ASA 650 mg

(enteric-coated). Nonmedicinal ingredients: black ferric oxide, carnauba

wax, cellulose acetate phthalate, cornstarch, diethyl phthalate, guar gum,

hydrogenated vegetable oil, hydroxypropyl cellulose, hydroxypropyl

methylcellulose, microcrystalline cellulose, sodium lauryl sulfate, sunset

yellow aluminum lake and titanium dioxide. Bottles of 50 (child-resistant

package) and 100.

Tablets: Each oval, orange, film-coated tablet, printed ENTROPHEN 650 mg in

black on one side, contains: ASA 650 mg (enteric-coated). Nonmedicinal

ingredients: black ferric oxide, carnauba wax, cellulose acetate phthalate,

cornstarch, diethyl phthalate, guar gum, hydrogenated vegetable oil,

hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline

cellulose, polyvinyl acetate phthalate, sodium lauryl sulfate, sunset yellow

aluminum lake and titanium dioxide. Bottles of 50 (child-resistant package),

100 and 1 000 (for dispensing use only).

15 Maximum Strength: Tablets: Each oval, pale yellow, film-coated tablet,

printed ENTROPHEN 975 mg in black on one side, contains: ASA 975 mg

(enteric-coated). Nonmedicinal ingredients: black ferric oxide, carnauba

wax, cellulose acetate phthalate, cornstarch, diethyl phthalate, guar gum,

hydrogenated vegetable oil, hydroxypropyl cellulose, hydroxypropyl

methylcellulose, microcrystalline cellulose, polyvinyl acetate phthalate,

sodium lauryl sulfate, titanium dioxide and yellow ferric oxide. Bottles of

50 (child-resistant package), 100 and 500 (for dispensing use only).

Store at 15 to 30°C. Protect from moisture.