CYTOPAN Tablet

For acute and chronic treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute musculoskeletal disorders.

The misoprostol component is indicated for the prevention of NSAIDs-induced gastric and duodenal ulcers.

Dosage and Administration

Osteoarthritis:

The recommended dosage for maximal GI mucosal protection is CYTOPAN 50 tablets t.i.d. For patients who experience intolerance, CYTOPAN 75 tablets b.i.d. can be used, but are less effective in preventing ulcers.

Rheumatoid Arthritis:

The recommended dosage is CYTOPAN 50 tablets t.i.d. or q.i.d. For patients who experience intolerance, CYTOPAN 75 tablets b.i.d. can be used, but are less effective in preventing ulcers.

Ankylosing Spondylitis:

The recommended dosage is CYTOPAN 50 tablets t.i.d. or q.i.d.

Acute Musculoskeletal Disorders

The recommended dosage for maximal GI mucosal protection is CYTOPAN 50 tablets b.i.d. or t.i.d.

Special Dosing Considerations:

CYTOPAN 50 & CYTOPAN 75 contains misoprostol, which provides protection against gastric and duodenal ulcers. For gastric ulcer prevention, the 200mcg q.i.d. and t.i.d. regimens are therapeutically equivalent, but more protective than the b.i.d. regimen.

For duodenal ulcer prevention, the q.i.d. regimen is more protective than the t.i.d. or b.i.d. regimens. However, the q.i.d. regimen is less well tolerated than the t.i.d. regimen and the b.i.d. regimen may be better tolerated than t.i.d. in some patients.

Note: The total dose of misoprostol should not exceed 800mcg/day, and no more than 200mcg of misoprostol should be administered at any one time. Doses of diclofenac sodium higher than 150mg/day in osteoarthritis or higher than 225mg/day in rheumatoid arthritis are not recommended.

- In patients with hypersensitivity to diclofenac sodium or to misoprostol or other prostaglandins.

- In pregnant women, because its misoprostol component can cause abortion.

- Should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.

- is not recommended for use in patients having advanced kidney disease.

- is not recommended in combination with aspirin and magnesium containing antacids.

- is not recommended for use in patients with active liver disease

- is contraindicated in lactating patients.

The most common adverse reactions encountered with NSAIDs are gastrointestinal, of which peptic ulcer, with or without bleeding, is the most severe. The following adverse reactions occurred:

Gastrointestinal: abdomen enlarged, esophageal ulceration, gall bladder disorder, glossitis, hematemesis, hiccup and melena.

CNS/Psychiatric: anorexia, anxiety, concentration impaired, depression, hypoesthesia, dry mouth, speech disorder and vertigo.

Dermatologic: angioedema, erythema multiforme, sweating increased and urticaria.

Cardiovascular: palpitation and syncope.

Special Senses: earache, eye pain, taste loss, taste abnormalities, tinnitus and vision abnormal.

Hematologic: leukopenia and thrombocytopenia.

Hepatic: bilirubinemia, abnormal hepatic function LDH increased, and alkaline phosphatase increased.

Metabolic: BUN increased and glycosuria.

Respiratory: hyperventilation and sputum increased.

Gynecological: menstrual disorder, intermenstrual bleeding, dysmenorrhea, leucorrhea, and vaginal bleeding.

Body as a Whole: hot flushes, malaise, rigors.

Urinary: dysuria abnormal urine, hematuria and cystitis.

See the package insert about the details below:

Digoxin

Antihypertensive agents

Warfarin

Oral hypoglycemics

Methotrexate and Cyclosporine

Lithium

Diuretics

Contraindicated

Because of the abortifacient property of misoprostol CYTOPAN 50 & CYTOPAN75 are contraindicated for use by pregnant women. Misoprostol may cause miscarriage if given to pregnant women at any time during pregnancy. Miscarriages caused by misoprostol may be incomplete, which could lead to dangerous bleeding, hospitalization, surgery, infertility, or maternal or fetal death. Patients must be advised of the abortifacient property and warned not to give the drug to others.

Special note for women: See “Pregnancy and Lactation”.

Gastrointestinal effects - risk of GI ulceration, bleeding and perforation

Serious GI toxicity, such as inflammation, bleeding, ulceration and perforation of the stomach, small intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Minor upper GI problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy.

Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms. Patients should be informed about the signs and/or symptoms and the steps to take if they occur.

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or GI bleeding.

Precautions

General: Diclofenac sodium + misoprostol combination cannot be used to substitute for corticosteroids or to treat for corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

(See the package insert about the details below.)

Renal effects

Haematologic effects

Fluid retention and edema

Pre-existing asthma

Geriatric use

Diclofenac Sodium

The mechanism of action is not completely understood but may be related to prostaglandin synthetase inhibition.

Misoprostol

It inhibits basal and nocturnal gastric acid secretion through a direct action on the parietal cell. Misoprostol also exerts a mucosal protectant effect that may contribute to its effectiveness in treating ulcers.