DRUGS & SUPPLEMENTS
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Cyclo-Meff (Dicyclomine Hydrochloride) is an antispasmodic and anticholinergic (antimuscarinic) agent. Cyclo-Meff (Dicyclomine Hydrochloride) occurs as a fine, white, crystalline, practically odorless powder with a bitter taste. It is soluble in water, freely soluble in alcohol and chloroform, and very slightly soluble in ether.
Chemically, it is [Bicyclohexyl]-1-carboxylic acid, 2-(diethyl-amino) ethyl ester, hydrochloride with the following structural formula:
Each capsule, for oral administration, contains 10 mg of Cyclo-Meff (Dicyclomine Hydrochloride).
Each tablet, for oral administration, contains 20 mg of Cyclo-Meff (Dicyclomine Hydrochloride).
This product contains the following inactive ingredients: colloidal silicon dioxide (tablets only), corn starch (tablets only), D&C red #28 (capsules only), FD&C blue #1 (capsules only), FD&C blue #1 lake (tablets only), FD&C red #40 (capsules only), gelatin (capsules only), hypromellose (tablets only), lactose monohydrate (tablets only), magnesium stearate (capsules only), pregelatinized starch, silicon dioxide (capsules only), sodium lauryl sulfate (capsules only), sodium starch glycolate (tablets only), and stearic acid (tablets only).
Dicyclomine relieves smooth muscle spasm of the gastrointestinal tract. Animal studies indicate that this action is achieved via a dual mechanism: (1) a specific anticholinergic effect (antimuscarinic) at the acetylcholine- receptor sites with approximately 1/8 the milligram potency of atropine (in vitro, guinea pig ileum); and (2) a direct effect upon smooth muscle (musculotropic) as evidenced by dicyclomine's antagonism of bradykinin- and histamine-induced spasms of the isolated guinea pig ileum. Atropine did not affect responses to these two agonists. In vivo studies in cats and dogs showed dicyclomine to be equally potent against acetylcholine (ACh)- or barium chloride (BaCI2)- induced intestinal spasm while atropine was at least 200 times more potent against effects of ACh than BaCI2. Tests for mydriatic effects in mice showed that dicyclomine was approximately 1/500 as potent as atropine; antisialogogue tests in rabbits showed dicyclomine to be 1/300 as potent as atropine.
In man, dicyclomine is rapidly absorbed after oral administration, reaching peak values within 60-90 minutes. The principal route of elimination is via the urine (79.5% of the dose). Excretion also occurs in the feces, but to a lesser extent (8.4%). Mean half-life of plasma elimination in one study was determined to be approximately 1.8 hours when plasma concentrations were measured for 9 hours after a single dose. In subsequent studies, plasma concentrations were followed for up to 24 hours after a single dose, showing a secondary phase of elimination with a somewhat longer half-life. Mean volume of distribution for a 20 mg oral dose is approximately 3.65 L/kg suggesting extensive distribution in tissues.
In controlled clinical trials involving over 100 patients who received drug, 82% of patients treated for functional bowel/irritable bowel syndrome with Cyclo-Meff (Dicyclomine Hydrochloride) at initial doses of 160 mg daily (40 mg q.i.d.) demonstrated a favorable clinical response compared with 55% treated with placebo (p<.05). In these trials, most of the side effects were typically anticholinergic in nature and were reported by 61% of the patients.
|(40 mg q.i.d.)||Placebo|
Nine percent (9%) of patients were discontinued from the drug because of one or more of these side effects (compared with 2% in the placebo group). In 41% of the patients with side effects, side effects disappeared or were tolerated at the 160 mg daily dose without reduction. A dose reduction from 160 mg daily to an average daily dose of 90 mg was required in 46% of the patients with side effects who then continued to experience a favorable clinical response; their side effects either disappeared or were tolerated.
For the treatment of functional bowel/irritable bowel syndrome.
Obstructive disease of the gastrointestinal tract
Severe ulcerative colitis
Unstable cardiovascular status in acute hemorrhage
Evidence of prior hypersensitivity to Cyclo-Meff (Dicyclomine Hydrochloride) or other ingredients of these formulations
Infants less than 6 months of age
In the presence of a high environmental temperature, heat prostration can occur with drug use (fever and heat stroke due to decreased sweating). If symptoms occur, the drug should be discontinued and supportive measures instituted.
Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance, treatment with this drug would be inappropriate and possibly harmful.
Dicyclomine may produce drowsiness or blurred vision. The patient should be warned not to engage in activities requiring mental alertness, such as operating a motor vehicle or other machinery or performing hazardous work while taking this drug.
Psychosis has been reported in sensitive individuals given anticholinergic drugs. CNS signs and symptoms include confusion, disorientation, short-term memory loss, hallucinations, dysarthria, ataxia, coma, euphoria, decreased anxiety, fatigue, insomnia, agitation and mannerisms, and inappropriate affect. These CNS signs and symptoms usually resolve within 12 to 24 hours after discontinuation of the drug.
There are reports that administration of dicyclomine syrup to infants has been followed by serious respiratory symptoms (dyspnea, shortness of breath, breathlessness, respiratory collapse, apnea, asphyxia), seizures, syncope, pulse rate fluctuations, muscular hypotonia, and coma. Death has been reported. No causal relationship between these effects observed in infants and dicyclomine administration has been established. DICYCLOMINE IS CONTRAINDICATED IN INFANTS LESS THAN 6 MONTHS OF AGE AND IN NURSING MOTHERS..
Safety and efficacy of Cyclo-Meff (Dicyclomine Hydrochloride) in pediatric patients have not been established.
Use with caution in patients with:
Hepatic or renal disease
Ulcerative colitis-large doses may suppress intestinal motility to the point of producing a paralytic ileus and the use of this drug may precipitate or aggravate the serious complication of toxic megacolon
Coronary heart disease
Congestive heart failure
Known or suspected prostatic hypertrophy.
Investigate any tachycardia before administration of Cyclo-Meff (Dicyclomine Hydrochloride), since it may increase the heart rate.
With overdosage, a curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).
Dicyclomine may produce drowsiness or blurred vision. The patient should be warned not to engage in activities requiring mental alertness, such as operating a motor vehicle or other machinery or to perform hazardous work while taking this drug.
Dicyclomine is contraindicated in infants less than 6 months of age and in nursing mothers..
In the presence of a high environmental temperature, heat prostration can occur with drug use (fever and heat stroke due to decreased sweating).
If symptoms occur, the drug should be discontinued and a physician contacted.
The following agents may increase certain actions or side effects of anticholinergic drugs: amantadine, antiarrhythmic agents of Class I, antihistamines, antipsychotic agents (e.g., phenothiazines), benzodiazepines, MAO inhibitors, narcotic analgesics (e.g., meperidine), nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants, and other drugs having anticholinergic activity.
Anticholinergics antagonize the effects of antiglaucoma agents. Anticholinergic drugs in the presence of increased intraocular pressure may be hazardous when taken concurrently with agents such as corticosteroids.
Anticholinergic agents may affect gastrointestinal absorption of various drugs, such as slowly dissolving dosage forms of digoxin; increased serum digoxin concentrations may result. Anticholinergic drugs may antagonize the effects of the drugs that alter gastrointestinal motility, such as metoclopramide. Because antacids may interfere with the absorption of anticholinergic agents, simultaneous use of these drugs should be avoided.
The inhibiting effects of anticholinergic drugs on gastric hydrochloric acid secretion are antagonized by agents used to treat achlorhydria and those used to test gastric secretion.
There are no known human data on long-term potential for carcinogenicity or mutagenicity.
Long-term studies in animals to determine carcinogenic potential are not known to have been conducted.
In studies in rats at doses of up to 100 mg/kg/day, dicyclomine produced no deleterious effects on breeding, conception, or parturition.
Pregnancy Category B.
Reproduction studies have been performed in rats and rabbits at doses up to 33 times the maximum recommended human dose based on 160 mg/day and have revealed no evidence of impaired fertility or harm to the fetus due to dicyclomine. Epidemiologic studies in pregnant women with products containing Cyclo-Meff (Dicyclomine Hydrochloride) (at doses up to 40 mg/day) have not shown that dicyclomine increases the risk of fetal abnormalities if administered during the first trimester of pregnancy. There are, however, no adequate and well-controlled studies in pregnant women at the recommended doses (80-160 mg/day). Because animal reproduction studies are not always predictive of human response, dicyclomine as indicated for functional bowel/irritable bowel syndrome should be used during pregnancy only if clearly needed.
Since dicyclomine has been reported to be excreted in human milk, Cyclo-Meff (Dicyclomine Hydrochloride) IS CONTRAINDICATED IN NURSING MOTHERS..
DICYCLOMINE IS CONTRAINDICATED IN INFANTS LESS THAN 6 MONTHS OF AGE.
Safety and effectiveness in pediatric patients have not been established.
Controlled clinical trials have provided frequency information for reported adverse effects of Cyclo-Meff (Dicyclomine Hydrochloride) listed in a decreasing order of frequency.
Not all of the following adverse reactions have been reported with Cyclo-Meff (Dicyclomine Hydrochloride). Adverse reactions are included here that have been reported for pharmacologically similar drugs with anticholinergic/antispasmodic action.
Gastrointestinal: dry mouth, nausea, vomiting, constipation, bloated feeling, abdominal pain, taste loss, anorexia
Central Nervous System: dizziness, light-headedness, tingling, headache, drowsiness, weakness, nervousness, numbness, mental confusion and/or excitement (especially in elderly persons), dyskinesia, lethargy, syncope, speech disturbance, insomnia
Ophthalmologic: blurred vision, diplopia, mydriasis, cycloplegia, increased ocular tension
Dermatological/Allergic: rash, urticaria, itching, and other dermal manifestations; severe allergic reaction or drug idiosyncrasies including anaphylaxis
Genitourinary: urinary hesitancy, urinary retention
Cardiovascular: tachycardia, palpitations
Respiratory: Dyspnea, apnea, asphyxia
Other: decreased sweating, nasal stuffiness or congestion, sneezing, throat congestion, impotence, suppression of lactation
Abuse of and/or dependence on dicyclomine for anticholinergic effects have been rarely reported.
The signs and symptoms of overdosage are headache; nausea; vomiting; blurred vision; dilated pupils; hot, dry skin; dizziness; dryness of the mouth; difficulty in swallowing; and CNS stimulation. A curare-like action may occur.
A 37-year-old female reported numbness on the left side, cold fingertips, blurred vision, abdominal and flank pain, decreased appetite, dry mouth, and nervousness following ingestion of 320 mg daily (four 20 mg tablets QID) for four days. These events resolved after discontinuing the dicyclomine.
The acute oral LD50 of the drug is 625 mg/kg in mice.
Minimum Human Lethal Dose/Maximum Human Dose Recorded
The amount of drug in a single dose that is ordinarily associated with symptoms of overdosage or that is Iikely to be life threatening, has not been defined. The maximum human oral dose recorded was 600 mg by mouth in a 10-month-old child and approximately 1500 mg in an adult, each of whom survived.
In three of the infants who died following administration of Cyclo-Meff (Dicyclomine Hydrochloride), the blood concentrations of drug were 200, 220, and 505 ng/mL, respectively.
It is not known if dicyclomine is dialyzable.
Treatment should consist of gastric lavage, emetics, and activated charcoal. Sedatives (e.g., short-acting barbiturates, benzodiazepines) may be used for management of overt signs of excitement. If indicated, an appropriate parenteral cholinergic agent may be used as an antidote.
DOSAGE MUST BE ADJUSTED TO INDIVIDUAL PATIENT NEEDS.
The only oral dose clearly shown to be effective is 160 mg per day (in 4 equally divided doses). Since this dose is associated with a significant incidence of side effects, it is prudent to begin with 80 mg per day (in 4 equally divided doses). Depending upon the patient's response during the first week of therapy, the dose should be increased to 160 mg per day unless side effects limit dosage escalation.
If efficacy is not achieved within 2 weeks or side effects require doses below 80 mg per day, the drug should be discontinued. Documented safety data are not available for doses above 80 mg daily for periods longer than 2 weeks.
The intramuscular dosage form is to be used temporarily when the patient cannot take oral medication. Intramuscular injection is about twice as bioavailable as oral dosage forms; consequently, the recommended intramuscular dose is 80 mg daily (in 4 equally divided doses).
Oral Cyclo-Meff (Dicyclomine Hydrochloride) should be started as soon as possible and the intramuscular form should not be used for periods longer than 1 or 2 days.
Cyclo-Meff Capsules USP and Cyclo-Meff (Dicyclomine Hydrochloride) Tablets USP are supplied as follows:
10 mg capsules: Clear Dark Blue cap/Clear Dark Blue body hard gelatin capsules, imprinted with white ink WATSON over 794 on cap and 10 mg on the body, in bottles of 100 and 1000.
20 mg tablets: Blue, round, unscored, flat-faced, beveled-edge tablets, debossed WATSON and 795 on the periphery on one side and plain on the other side, in bottles of 100 and 1000.
Store at controlled room temperature 15°-30°C (59°-86°F).
Dispense in a well-closed container as defined in USP/NF.
Watson Laboratories, Inc.
Corona, CA 92880 USA
Patheon Pharmaceuticals Inc.
Cincinnati, OH 45215 USA
Carefully consider the potential benefits and risks of Cyclo-Meff (Mefenamic Acid) and other treatment options before deciding to use Cyclo-Meff (Mefenamic Acid). Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation ).
Cyclo-Meff (Mefenamic Acid) is indicated:
Cyclo-Meff (Mefenamic Acid) is contraindicated in the following patients:
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as Cyclo-Meff (Mefenamic Acid), increases the risk of serious gastrointestinal (GI) events (see WARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation ).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS).
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.
Avoid the use of Cyclo-Meff in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Cyclo-Meff (Mefenamic Acid) is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
NSAIDs, including Cyclo-Meff (Mefenamic Acid), cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.
Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy, concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors ; smoking, use of alcohol, older age, and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.
Elevations of ALT or AST have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported.
Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with NSAIDs including Cyclo-Meff (Mefenamic Acid).
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Cyclo-Meff (Mefenamic Acid) immediately, and perform a clinical evaluation of the patient.
NSAIDs, including Cyclo-Meff (Mefenamic Acid), can lead to new onset of hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazides diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs (see PRECAUTIONS; Drug Interactions ).
Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.
The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of Cyclo-Meff may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) (see PRECAUTIONS; Drug Interactions ).
Avoid the use of Cyclo-Meff (Mefenamic Acid) in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Cyclo-Meff (Mefenamic Acid) is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of Cyclo-Meff in patients with advanced renal disease. The renal effects of Cyclo-Meff (Mefenamic Acid) may hasten the progression of renal dysfunction in patients with pre-existing renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating Cyclo-Meff (Mefenamic Acid). Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of Cyclo-Meff (Mefenamic Acid) (see PRECAUTIONS; Drug Interactions ). Avoid the use of Cyclo-Meff (Mefenamic Acid) in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If Cyclo-Meff (Mefenamic Acid) is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
Cyclo-Meff has been associated with anaphylactic reactions in patients with and without known hypersensitivity to Cyclo-Meff (Mefenamic Acid) and in patients with aspirin-sensitive asthma (see CONTRAINDICATIONS , WARNINGS; Exacerbation of Asthma Related to Aspirin Sensitivity).
Seek emergency help if anaphylactic reaction occurs.
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Cyclo-Meff (Mefenamic Acid) is contraindicated in patients with this form of aspirin sensitivity (see CONTRAINDICATIONS ). When Cyclo-Meff (Mefenamic Acid) is used in patients with pre-existing asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
NSAIDs, including Cyclo-Meff, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions and to discontinue the use of Cyclo-Meff (Mefenamic Acid) at the first appearance of skin rash or any other sign of hypersensitivity. Cyclo-Meff (Mefenamic Acid) is contraindicated in patients with previous serious skin reactions to NSAIDs (see CONTRAINDICATIONS ).
Cyclo-Meff (Mefenamic Acid) may cause premature closure of the ductus arteriosus. Avoid use of NSAIDs, including Cyclo-Meff (Mefenamic Acid), in pregnant women starting at 30 weeks of gestation (third trimester) (see PRECAUTIONS; Pregnancy ).
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with Cyclo-Meff (Mefenamic Acid) has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including Cyclo-Meff (Mefenamic Acid), may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding .
Cyclo-Meff cannot be expected to substitute for corticosteroids or to treat 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.
Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed. Inform patients, families and their caregivers of the following information before initiating therapy with Cyclo-Meff (Mefenamic Acid) and periodically during the course of ongoing therapy.
Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately.
Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their healthcare provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding (see WARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation).
Inform patients of the warning signs and symptoms of hepatotoxicity. If these occur, instruct patients to stop Cyclo-Meff (Mefenamic Acid) and seek immediate medical therapy (see WARNINGS; Hepatotoxicity ).
Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see WARNINGS; Heart Failure and Edema ).
Inform patients of the signs of an anaphylactic reaction. Instruct patients to seek immediate emergency help if these occur (see CONTRAINDICATIONS, WARNINGS; Anaphylactic Reactions ).
Advise patients to stop Cyclo-Meff (Mefenamic Acid) immediately if they develop any type of rash and contact their healthcare provider as soon as possible (see WARNINGS; Serious Skin Reactions ).
Advise females of reproductive potential who desire pregnancy that NSAIDs, including Cyclo-Meff, may be associated with a reversible delay in ovulation. .
Inform pregnant women to avoid use of Cyclo-Meff (Mefenamic Acid) and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closure of the fetal ductus arteriosus (see WARNINGS; Premature Closure of Fetal Ductus Arteriosus ).
Inform patients that the concomitant use of Cyclo-Meff with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy (see WARNINGS; Gastrointestinal Bleeding, Ulceration and Perforation, PRECAUTIONS; Drug Interactions ). Alert patients that NSAIDs may be present in "over the counter" medications for treatment of colds, fever, or insomnia.
Inform patients not to use low-dose aspirin concomitantly with Cyclo-Meff (Mefenamic Acid) until they talk to their healthcare provider .
The pharmacological activity of Cyclo-Meff in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile checked periodically (see WARNINGS; Gastrointestinal Bleeding, Ulceration and Perforation, and Hepatotoxicity ).
|Drugs That Interfere with Hemostasis|
|Clinical Impact:|| |
|Intervention:||Monitor patients with concomitant use of Cyclo-Meff (Mefenamic Acid) with anticoagulants (e.g.,warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding (see WARNINGS; Hematologic Toxicity).|
|Clinical Impact:||Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone .|
|Intervention:||Concomitant use of Cyclo-Meff (Mefenamic Acid) and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding (see WARNINGS; Hematologic Toxicity). |
Cyclo-Meff (Mefenamic Acid) is not a substitute for low dose aspirin for cardiovascular protection.
|ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers|
|Clinical Impact:|| |
|Clinical Impact:||Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.|
|Intervention||During concomitant use of Cyclo-Meff (Mefenamic Acid) with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects .|
|Clinical Impact:||The concomitant use of Cyclo-Meff (Mefenamic Acid) with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.|
|Intervention:||During concomitant use of Cyclo-Meff (Mefenamic Acid) and digoxin, monitor serum digoxin levels.|
|Clinical Impact:||NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.|
|Intervention:||During concomitant use of Cyclo-Meff (Mefenamic Acid) and lithium, monitor patients for signs of lithium toxicity.|
|Clinical Impact:||Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).|
|Intervention:||During concomitant use of Cyclo-Meff (Mefenamic Acid) and methotrexate, monitor patients for methotrexate toxicity.|
|Clinical Impact:||Concomitant use of Cyclo-Meff (Mefenamic Acid) and cyclosporine may increase cyclosporine's nephrotoxicity.|
|Intervention:||During concomitant use of Cyclo-Meff (Mefenamic Acid) and cyclosporine, monitor patients for signs of worsening renal function.|
|NSAIDs and Salicylates|
|Clinical Impact:||Concomitant use of Cyclo-Meff (Mefenamic Acid) with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy .|
|Intervention:||The concomitant use of Cyclo-Meff (Mefenamic Acid) with other NSAIDs or salicylates is not recommended.|
|Clinical Impact:||Concomitant use of Cyclo-Meff (Mefenamic Acid) and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity.|
|Intervention:||During concomitant use of Cyclo-Meff (Mefenamic Acid) and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. |
NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed.
In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.
|Clinical Impact:||In a single dose study (n=6), ingestion of an antacid containing 1.7-gram of magnesium hydroxide with 500-mg of Cyclo-Meff (Mefenamic Acid) increased the Cmax and AUC of Cyclo-Meff (Mefenamic Acid) by 125% and 36%, respectively.|
|Intervention:||Concomitant use of Cyclo-Meff (Mefenamic Acid) and antacids is not generally recommended because of possible increased adverse events.|
Cyclo-Meff (Mefenamic Acid) may prolong prothrombin time. Therefore, when the drug is administered to patients receiving oral anticoagulant drugs, frequent monitoring of prothrombin time is necessary.
A false-positive reaction for urinary bile, using the diazo tablet test, may result after Cyclo-Meff (Mefenamic Acid) administration. If biliuria is suspected, other diagnostic procedures, such as the Harrison spot test, should be performed.
Long-term studies in animals to evaluate the carcinogenic potential of Cyclo-Meff have not been conducted.
Studies to evaluate the mutagenic potential of Cyclo-Meff (Mefenamic Acid) have not been completed.
Dietary administration of Cyclo-Meff to male rats 61 days- and to female rats 15 days- prior to mating through to Gestation Day (GD) 21 at a dose of 155 mg/kg/day (equivalent to the Maximum Recommended Human Dose [MRHD] of 1500 mg/day on a mg/m2 basis) resulted in decreased corpora lutea.
In another study, rats administered up to 10-times a human dose of 250 mg showed decreased fertility.
Use of NSAIDs, including Cyclo-Meff, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Cyclo-Meff (Mefenamic Acid), in pregnant women starting at 30 weeks of gestation (third trimester) .
There are no adequate and well-controlled studies of Cyclo-Meff (Mefenamic Acid) in pregnant women.
Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies in rats and rabbits when dosed throughout gestation, there were no evidence of developmental effects at a dose of Cyclo-Meff (Mefenamic Acid) 1.6-times and 0.6-times the maximum recommended human dose (MRHD), respectively. Dietary administration of Cyclo-Meff (Mefenamic Acid) at a dose 1.2-times the MRHD from gestation day (GD) 15 to weaning or at a dose equivalent to the MRHD from 15 days prior to mating through to weaning resulted in greater incidences of perinatal death . Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as Cyclo-Meff (Mefenamic Acid), resulted in increased pre- and post-implantation loss.
Pregnant rats administered 249 mg/kg of Cyclo-Meff (1.6-times the MRHD of 1500 mg/day on a mg/m2 basis) from GD 6 to GD 15 did not result in any clear adverse developmental effects.
Pregnant rabbits given 50 mg/kg of Cyclo-Meff (Mefenamic Acid) (0.6-times the MRHD on a mg/m2 basis) from GD 6 to GD 18 did not result in any clear treatment-related adverse developmental effects. However, incidences of resorption were greater in treated compared to control animals. This dose was associated with some evidence of maternal toxicity with 4 of 18 rabbits exhibiting diarrhea and weight loss.
Dietary administration of Cyclo-Meff (Mefenamic Acid) at a dose of 181 mg/kg (1.2-times the MRHD on a mg/m2 basis) to pregnant rats from GD 15 to weaning resulted in an increased incidence of perinatal death. Treated dams were associated with decreased weight gain and delayed parturition. In another study, dietary administration of Cyclo-Meff (Mefenamic Acid) at a dose of 155 mg/kg (equivalent to the MRHD of 1500 mg/day on a mg/m2 basis) to females 15 days prior to mating through to weaning resulted in smaller average litter sizes and higher incidence of perinatal death.
In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, decreased pup survival occurred and increased the incidence of stillbirth. The effects of Cyclo-Meff (Mefenamic Acid) on labor and delivery in pregnant women are unknown.
Trace amounts of Cyclo-Meff may be present in breast milk and transmitted to the nursing infant. Because of the potential for serious adverse reactions in nursing infants from Cyclo-Meff (Mefenamic Acid), 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.
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Cyclo-Meff may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin in mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including Cyclo-Meff (Mefenamic Acid), in women who have difficulties conceiving or who are undergoing investigation of infertility.
Safety and effectiveness in pediatric patients below the age of 14 have not been established.
Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects .
Clinical studies of Cyclo-Meff (Mefenamic Acid) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. As with any NSAID, caution should be exercised in treating the elderly (65 years and older).
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (See CLINICAL PHARMACOLOGY, ADVERSE REACTIONS ).
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In patients taking Cyclo-Meff (Mefenamic Acid) or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are:
Gastrointestinal experiences including - abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting, abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, tinnitus
Additional adverse experiences reported occasionally and listed here by body system include:
Body as a whole - fever, infection, sepsis
Cardiovascular system - congestive heart failure, hypertension, tachycardia, syncope
Digestive system - dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice
Hemic and lymphatic system - ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia
Metabolic and nutritional - weight changes
Nervous system - anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness; insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo
Respiratory system - asthma, dyspnea
Skin and appendages - alopecia, photosensitivity, pruritus, sweat
Special senses - blurred vision
Urogenital system - cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure
Other adverse reactions, which occur rarely are:
Body as a whole - anaphylactoid reactions, appetite changes, death
Cardiovascular system - arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis
Digestive system - eructation, liver failure, pancreatitis
Hemic and lymphatic system - agranulocytosis, hemolytic anemia, aplastic anemia, lymph-adenopathy, pancytopenia
Metabolic and nutritional - hyperglycemia
Nervous system - convulsions, coma, hallucinations, meningitis
Respiratory - respiratory depression, pneumonia
Skin and appendages - angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria
Special senses - conjunctivitis, hearing impairment
Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression and coma have occurred, but were rare .
Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdose (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
For additional information about overdosage treatment, contact a poison control center (1-800-222-1222).
Carefully consider the potential benefits and risks of Cyclo-Meff (Mefenamic Acid) and other treatment options before deciding to use Cyclo-Meff (Mefenamic Acid). Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation ).
After observing the response to initial therapy with Cyclo-Meff (Mefenamic Acid), the dose and frequency should be adjusted to suit an individual patient's needs.
For the relief of acute pain in adults and adolescents ≥14 years of age, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours as needed, usually not to exceed one week.
For the treatment of primary dysmenorrhea, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours, given orally, starting with the onset of bleeding and associated symptoms. Clinical studies indicate that effective treatment can be initiated with the start of menses and should not be necessary for more than 2 to 3 days.
Cyclo-Meff (mefenamic acid) is available as 250 mg blue-banded, ivory capsules, imprinted with " FHPC 400" and "PONSTEL®".
|Bottles of 30||NDC 59630-400-30|
Dispense in a tight container as defined in the USP.
Store at room temperature 20° to 25°C (68°to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
Florham Park, NJ 07932
Halo Pharmaceutical Inc.
Whippany, NJ 07981
For inquires call 1-800-849-9707
|This Medication Guide has been approved by the U.S. Food and Drug Administration. |
|Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDS)|
| What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)? |
NSAID can cause serious side effects, including:
Do not take NSAIDs right before or after a heart surgery called a "coronary artery bypass graft (CABG)". Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.
The risk of getting an ulcer or bleeding increases with:
| || |
| NSAID should only be used: |
| What are NSAIDs? |
NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.
| Who should not take NSAIDs? |
Do not take NSAIDs:
| Before taking NSAIDs, tell our healthcare provider about all of your medical conditions, including if you: |
Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins, or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.
| What are the possible side effects of NSAIDs? |
NSAIDs can cause serious side effects, including:
See "What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?
Get emergency help right away if you get any of the following symptoms:
| || |
|Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:|
| || |
| If you take too much of your NSAID, call your healthcare provider or get medical help right away. |
These are not all of the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
| Other information about NSAIDs |
| General information about the safe and effective use of NSAIDs |
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them.
If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.
|Manufactured for: SHIONOGI INC., Florham Park, NJ 07932 |
Manufactured by: HALO PHARMACEUTICAL INC., Whippany, NJ 07981
For more information, call 1-800-849-9707
Cyclo-Meff (Mefenamic Acid)®
(Mefenamic Acid Capsules, USP)
PHARMACIST: PLEASE DISPENSE
WITH MEDICATION GUIDE
Depending on the reaction of the Cyclo-Meff after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Cyclo-Meff not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Cyclo-Meff addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology