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Introduction
Misoclo is a combination product containing Diclofenac sodium, a
nonsteroidal anti-inflammatory drug (NSAID) with analgesic
properties, and Misoprostol, a gastrointestinal (GI) mucosal
protective synthetic prostaglandin E1 analogue.
Composition
Each tablet consists of an enteric-coated core containing 50 mg
Diclofenac sodium surrounded by an outer mantle containing 200 mcg
misoprostol. Diclofenac sodium is sparingly soluble in water. Its
chemical formula and name are: C14H10Cl2NO2Na [M.W. = 318.14]
2-[(2,6-dichlorophenyl) amino] benzene acetic acid, monosodium salt.
Misoprostol is a water-soluble, viscous liquid that contains
approximately equal amounts of two diastereomers. Its chemical
formula and name are:
C22H38O5 [M.W. = 382.54] (±) methyl 11a,
16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate.
Pharmacodynamics
Misoprostol is a synthetic prostaglandin E1 analog with gastric anti
secretory and (in animals) mucosal protective properties. NSAIDs
inhibit prostaglandin synthesis. A deficiency of prostaglandins
within the gastric and duodenal mucosa may lead to diminishing
bicarbonate and mucus secretion and may contribute to the mucosal
damage caused by NSAIDs. Misoprostol can increase bicarbonate and
mucus production, but in humans this has been shown at doses 200 mcg
and above that are also anti secretory. It is therefore not possible
to tell whether the ability of misoprostol to prevent gastric and
duodenal ulcers is the result of its anti secretory effect, its
mucosal protective effect, or both. Misoprostol produces a moderate
decrease in pepsin concentration during basal conditions, but not
during histamine stimulation. It has no significant effect on
fasting or postprandial gastrin nor intrinsic factor output. Orally
administered misoprostol is rapidly and extensively absorbed, and it
undergoes rapid metabolism to its biologically active metabolite,
misoprostol acid.
Indications
Misoclo is indicated for treatment of the signs and symptoms of
osteoarthritis or rheumatoid arthritis in patients at high risk of
developing NSAID-induced gastric and duodenal ulcers and their
complications.
Dosage and Administration
Misoclo is administered as Misoclo 50 (50 mg diclofenac sodium/200
mcg misoprostol).
Osteoarthritis: The recommended
dosage for maximal GI mucosal protection is Misoclo 50 tid. For
patients who experience intolerance, Misoclo 50 bid can be used, but
are less effective in preventing ulcers.
Rheumatoid Arthritis: The
recommended dosage is Misoclo 50 tid or qid. For patients who
experience intolerance, Misoclo 50 bid can be used, but are less
effective in preventing ulcers.
Advanced renal disease: In
patients with advanced kidney disease, treatment with Misoclo is not
recommended. If NSAID therapy must be initiated however, close
monitoring of the patient's kidney function is advisable.
Hepatic effects: Elevations of
one or more liver enzyme is seen in clinical trials, post marketing
surveillance has found rare cases of severe hepatic reactions,
including liver necrosis, jaundice, and fulminant fatal hepatitis
with and without jaundice.
Contraindications
Misoclo is contraindicated in patients with hypersensitivity to
diclofenac or to misoprostol or other prostaglandins. Misoclo should
not be given to patients who have experienced asthma, urticaria, or
other allergic-type reactions after taking aspirin or other NSAIDs.
Severe, rarely fatal, anaphylactic-like reactions to diclofenac
sodium have been reported. |
Side Effects
4
Belly pain, heartburn, cramps, gas, nausea,
4
Small frequent meals, frequent mouth care, sucking hard candy may
help.
4
Diarrhea. Take with meals. Use antacids without magnesium.
Precautions
Misoclo contains misoprostol. Because of its abortifacient property,
misoprostol is 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.
Use in Pregnancy & Lactation
Misoclo is not recommended for use by pregnant & nursing mothers.
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. As with any NSAID, the
elderly are likely to tolerate adverse events less well than younger
patients.
Drug Interactions
4Aspirin:
Concomitant administration of Misoclo and aspirin is not
recommended.
4
Digoxin: Elevated digoxin levels have been reported in patients
receiving digoxin and diclofenac sodium. Patients receiving digoxin
and Misoclo should be monitored for possible digoxin toxicity.
4
Antihypertensive agents: NSAIDs can inhibit the activity of
antihypertensives, including ACE inhibitors. Thus, caution should be
taken when administering Misoclo with such agents.
4
Warfarin: The effects of warfarin and NSAIDs on GI bleeding are
synergistic
4
Oral hypoglycemics: Diclofenac sodium does not alter glucose
metabolism in healthy people nor does it alter the effects of oral
hypoglycemic agents.
4
Methotrexate and cyclosporine: Ingestion of Misoclo may increase
serum concentrations of methotrexate and increase cyclosporine
nephrotoxicity.
4
Lithium: When NSAIDs and lithium are administered concurrently,
subjects should be observed carefully for signs of lithium toxicity.
4
Antacids: Antacids reduce the bioavailability of misoprostol acid.
Antacids may also delay absorption of diclofenac sodium.
4
Diuretics: The diclofenac sodium component of Misoclo, like other
NSAIDs, can inhibit the activity of diuretics.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies to evaluate the potential for
carcinogenesis and animal studies to evaluate the effects on
fertility have been performed with each component of Misoclo given
alone. Misoclo itself (diclofenac sodium and misoprostol
combinations in 250:1 ratio) was not genotoxic in the Ames test, the
Chinese hamster ovary cell (CHO/HGPRT) forward mutation test, the
rat lymphocyte chromosome aberration test or the mouse micronucleus
test.
Overdose
The toxic dose of Misoclo has not been determined.
Diclofenac sodium : Clinical signs that may suggest diclofenac
sodium overdose include GI complaints, confusion, drowsiness or
general hypotonia.
Misoprostol: The toxic dose of misoprostol in humans has not been
determined.
How Supplied
Each box contains 2 Blister strips of 10 enteric-coated tablets.
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