MEFAMIN D
The active ingredient of MEFAMIN D is Mefenamic Acid 250 Mg Dicyclomine Hydrochloride 10 mg. Mefenamic Acid is a non-steroidal anti-inflammatory drug (NSAID) which works by blocking the release of certain chemical messengers that cause abdominal pain and inflammation (swelling). Dicyclomine is an anticholinergic which works by relaxing the muscles in the stomach and gut (intestine). It stops sudden muscle contractions (spasms), thereby relieving cramps, pain, bloating, and discomfort. Together, they relieve menstrual cramps and colicky pain.
PRESENTATION:
Each Uncoated Tablet Contains Mefenamic Acid 250 mg, Dicyclomine Hydrochloride 10 mg.
Pack Size: 20*10 Blister
CLINICAL PARTICULARS
Therapeutic Indications
Mefenamic acid is a non-steroidal anti-inflammatory agent with analgesic properties, and a demonstrable antipyretic effect. It has been shown to inhibit prostaglandin activity.
Indications
Posology and Method of Administration
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
Do not exceed the stated dose.
Posology
Adults
1 -2 Tablet three times daily.
In menorrhagia to be administered on the first day of excessive bleeding and continued according to the judgment of the physician.
In dysmenorrhea to be administered at the onset of menstrual pain and continued according to the judgment of the physician.
Treatment is generally required till the time dysmenorrhea symptoms persist i.e., 3 to 5 days during the menses. Therapy should not be given for longer than 7 days at a time.
Elderly (over 65 years)
Elderly patients with normal renal function may be given the same dose as recommended for adults. Dicyclomine hydrochloride should be used with caution in elderly who may be more susceptible to its adverse effects. The elderly patients have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal (GI) bleeding and perforation which may be fatal. Thus, as like other NSAIDs, caution should be exercised while use of mefenamic acid in elderly population (> 65 years). Mefenamic acid is known to be substantially excreted by the kidney, and the risk of toxic reactions to it 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.
MEFAMIN D should be used with caution in elderly patients suffering from dehydration and renal disease. Non-oliguric renal failure and proctocolitis have been reported mainly in elderly patients who have not discontinued mefenamic acid after the development of diarrhea.
Pediatrics population
This formulation is not intended for use in children as there is no feasibility of dosage adjustments. Both, mefenamic acid and Dicyclomine are not recommended in infants less than 6 months of age. It is advised that children under 12 years of age should use pediatrics formulations of these drugs.
Method of Administration
For Oral Administration
MEFAMIN D Tablet should be taken preferably with or after food.
CONTRAINDICATIONS
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Mefenamic Acid
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. Patients on prolonged therapy should be kept under regular surveillance with particular attention to liver dysfunction, rash, blood dyscrasias or development of diarrhea. Appearance of any of these symptoms should be regarded as an indication to stop therapy immediately.
Use with concomitant NSAIDs including cyclooxygenase 2 specific inhibitors. Prolonged use of any type of painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained, and treatment should be discontinued. The diagnosis of 'Medication Overuse Headache' should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.
Precaution should be taken in patients suffering from dehydration and renal disease, particularly the elderly.
Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Respiratory Disorders: Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Cardiovascular, Renal and Hepatic Impairment: The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3).
Cardiovascular And Cerebrovascular Effects: Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and edema have been reported in association with NSAID therapy.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for mefenamic acid.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with mefenamic acid after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, and smoking).
As NSAIDs can interfere with platelet function, they should be used in caution in patients with intracranial hemorrhage and bleeding diathesis.
Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events. Smoking and alcohol use are added risk factors.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with hemorrhage or perforation, Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for patients at risk of GI bleeding such as the elderly, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk. Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of gastro toxicity or bleeding such as corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin. When GI bleeding or ulceration occurs in patients receiving mefenamic acid the treatment should be withdrawn.
SLE and mixed connective tissue disease: In patients with systemic lupus erythematous (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
Skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with use of NSAIDs. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Mefenamic acid should be stopped at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Female fertility: The use of mefenamic acid may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of mefenamic acid should be considered.
In dysmenorrhea and menorrhagia lack of response should alert the physician to investigate other causes.
Epilepsy: Caution should be exercised when treating patients suffering from epilepsy.
In patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates, mefenamic acid should be administered with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.
Alcohol: Concomitant consumption of alcohol with mefenamic acid may increase gastrointestinal bleeding, ulceration and perforation.
Dicyclomine Hydrochloride
Cardiovascular Conditions: Dicyclomine hydrochloride needs to be used with caution in conditions characterized by tachyarrhythmia such as thyrotoxicosis, congestive heart failure, and in cardiac surgery, where they may further accelerate the heart rate. Investigate any tachycardia before administration of Dicyclomine hydrochloride. Care is required in patients with coronary heart disease, as ischemia and infarction may be worsened, and in patients with hypertension.
Peripheral and Central Nervous System: The peripheral effects of Dicyclomine hydrochloride are a consequence of their inhibitory effect on muscarinic receptors of the autonomic nervous system. They include dryness of the mouth with difficulty in swallowing and talking, thirst, reduced bronchial secretions, dilatation of the pupils (mydriasis) with loss of accommodation (cycloplegia) and photophobia, flushing and dryness of the skin, transient bradycardia followed by tachycardia, with palpitations and arrhythmias, and difficulty in micturition, as well as reduction in the tone and motility of the gastrointestinal tract leading to constipation.
In the presence of high environmental temperature, heat prostration can occur with drug use (fever and heat stroke due to decreased sweating). It should also be used cautiously in patients with fever. If symptoms occur, the drug should be discontinued and supportive measures instituted. Because of the inhibitory effect on muscarinic receptors within the autonomic nervous system, caution should be taken in patients with autonomic neuropathy.
Central nervous system (CNS) signs and symptoms include confusional state, disorientation, amnesia, hallucinations, dysarthria, ataxia, coma, euphoria, fatigue, insomnia, agitation and mannerisms, and inappropriate affect. Psychosis and delirium have been reported in sensitive individuals (such as elderly patients and/or in patients with mental illness) given anticholinergic drugs. These CNS signs and symptoms usually resolve within 12 to 24 hours after discontinuation of the drug.
Myasthenia Gravis: With over dosage, a curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis). It should not be given to patients with myasthenia gravis except to reduce adverse muscarinic effects of an anticholinesterase.
Intestinal Obstruction: 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. Rarely, development of Ogilvie's syndrome (colonic pseudo-obstruction) has been reported. Ogilvie's syndrome is a clinical disorder with signs, symptoms, and radiographic appearance of an acute large bowel obstruction, but with no evidence of distal colonic obstruction.
Toxic Dilatation of Intestine (Mega colon): Toxic dilatation of intestine and intestinal perforation is possible when anticholinergic agents are administered in patients with Salmonella dysentery.
Ulcerative Colitis: Caution should be taken in patients with 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 mega colon. Dicyclomine is contraindicated in patients with severe ulcerative colitis.
Prostatic Hypertrophy: Dicyclomine should be used with caution in patients with known or suspected prostatic enlargement, in whom prostatic enlargement may lead to urinary retention.
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION
Concurrent therapy with other plasma protein binding drugs may necessitate a modification in dosage.
Anti-Coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4). Concurrent administration of mefenamic acid with oral anti-coagulant drugs requires careful prothrombin time monitoring. It is considered unsafe to take NSAIDs in combination with warfarin or heparin unless under direct medical supervision.
Lithium: A reduction in renal lithium clearance and elevation of plasma lithium levels. Patients should be observed carefully for signs of lithium toxicity.
The following interactions have been reported with NSAIDs but have not necessarily been associated with MEFAMIN D Tablets:
Other Analgesics Including Cyclooxygenase-2 Selective Inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects.
Antidepressants: Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Antihypertensive And Diuretics: A reduction in antihypertensive and diuretic effect has been observed. Diuretics can increase the nephrotoxicity of NSAIDs.
ACE Inhibitors and Angiotensin-II-Receptor Antagonists: A reduction in antihypertensive effect and an increased risk of renal impairment especially in elderly patients. Patients should be adequately hydrated, and the renal function assessed in the beginning and during concomitant therapy.
Aminoglycosides: Reduction in renal function in susceptible individuals, decreased elimination of aminoglycoside and increased plasma concentrations.
Anti-platelet agents: Increased risk of gastrointestinal ulceration or bleeding.
Acetylsalicylic Acid: Experimental data implies that mefenamic acid interferes with the anti-platelet effect of low-dose aspirin when given concomitantly, and thus may interfere with aspirin's prophylactic treatment of cardiovascular disease. However, the limitations of this experimental data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular mefenamic acid use.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.
Cyclosporine: The risk of nephrotoxicity of cyclosporine may be increased with NSAIDs.
Corticosteroids: Concomitant use may increase the risk of gastrointestinal ulceration or bleeding.
Oral hypoglycemic agents: Inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycemia.
Methotrexate: Elimination of the drug can be reduced, resulting in increased plasma levels.
Mifepristone: NSAIDs should not be taken for 8-12 days after mifepristone administration, NSAIDs can reduce the effects of mifepristone.
Probenecid: Reduction in metabolism and elimination of NSAIDs and metabolites.
Quinolone antibiotics: Animal data indicates that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDS are given with tacrolimus.
Zidovudine: Increased risk of hematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and hematoma in HIV (+) hemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Abacavir: Dicyclomine may decrease the excretion rate of Abacavir which could result in a higher serum level.
Acarbose: Acarbose may decrease the excretion rate of Dicyclomine which could result in a higher serum level.
Aceclofenac: Aceclofenac may decrease the excretion rate of Dicyclomine which could result in a higher serum level.
Acemetacin: Acemetacin may decrease the excretion rate of Dicyclomine which could result in a higher serum level.
Acetaminophen: Acetaminophen may decrease the excretion rate of Dicyclomine which could result in a higher serum level.
Acetazolamide: Acetazolamide may increase the central nervous system depressant (CNS depressant) activities of Dicyclomine.
Acetophenazine: Acetophenazine may increase the central nervous system depressant (CNS depressant) activities of Dicyclomine.
Acetylsalicylic Acid: Acetylsalicylic acid may decrease the excretion rate of Dicyclomine which could result in a higher serum level.
Aclidinium: The risk or severity of adverse effects can be increased when Dicyclomine is combined with Aclidinium.
Acrivastine: Dicyclomine may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Alcohol: Alcohol may increase drowsiness caused by Dicyclomine.
Drink plenty of fluids: Dicyclomine may reduce sweating, increasing the risk of overheating in warm weather or during exercise.
FERTILITY, PREGNANCY AND LACTATION
Pregnancy
Mefenamic Acid: Pregnancy Category C; Dicyclomine: Pregnancy Category B. For this combination product, there are no adequate and well controlled studies available in pregnant women. Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the fetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labor may be delayed, and the duration increased with an increased bleeding tendency in both mother and child. NSAIDs should not be used during the first two trimesters of pregnancy or labor unless the potential benefit to the patient outweighs the potential risk to the fetus.
Epidemiological studies in pregnant women with products containing Dicyclomine hydrochloride (at doses up to 40 mg/day) have not shown that Dicyclomine hydrochloride increases the risk of fetal abnormalities if administered during the first trimester of pregnancy. Reproduction studies have been performed in rats and rabbits at doses of up to 100 times the maximum recommended dose (based on 60 mg/day for an adult person) and have revealed no evidence of impaired fertility or harm to the fetus due to Dicyclomine. Since the risk of teratogenicity cannot be excluded with absolute certainty for any product, the drug should be used during pregnancy only if clearly needed.
Breast-Feeding
Trace amounts of mefenamic acid may be present in breast milk and transmitted to the nursing infant. Therefore, mefenamic acid should not be taken by nursing mothers. Dicyclomine has been reported to be excreted in human milk. Use of Dicyclomine is contraindicated in nursing mothers. Because of the potential for serious adverse reactions in nursing infants, MEFAMIN D Tablets are contraindicated for use in lactation. If drug therapy is essential to mother, breastfeeding must be discontinued during treatment period.
Fertility
The use of mefenamic acid may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of mefenamic acid should be considered (see section 4.4).
Effects on Ability to Drive and Use Machines
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
UNDESIRABLE EFFECTS
Mefenamic Acid
The most frequently reported side effects associated with mefenamic acid involve the gastrointestinal tract.
Diarrhea occasionally occurs following the use of mefenamic acid. Although this may occur soon after starting treatment, it may also occur after several months of continuous use. The diarrhea has been investigated in some patients who have continued this drug in spite of its continued presence. These patients were found to have associated proctocolitis. If diarrhea does develop the drug should be withdrawn immediately and this patient should not receive mefenamic acid again.
Frequencies Are Not Known For The Following Adverse Reactions:
Blood and the Lymphatic System Disorders
Hemolytic anemia*, anemia, hypoplasia bone marrow, hematocrit decreased, thrombocytopenic purpura, temporary lowering of the white blood cell count (leukopenia) with a risk of infection, sepsis, and disseminated intravascular coagulation.
Agranulocytosis, aplastic anemia, eosinophilia, neutropenia, pancytopenia, thrombocytopenia.
*reversible when mefenamic acid is stopped
Immune System Disorders
Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of
(a) Non-specific allergic reactions and anaphylaxis
(b) Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm, or dyspnea
(c) Assorted skin disorders including rashes of various types, pruritus, urticaria, purpura, angioedema, and more rarely exfoliative or bullous dermatoses (including epidermal necrolysis and erythema multiform).
Metabolism and Nutrition Disorders
Glucose intolerance in diabetic patients, hyponatraemia.
Psychiatric Disorders
Confusion, depression, hallucinations, nervousness.
Nervous System Disorders
Optic neuritis, headaches, paresthesia, dizziness, drowsiness, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematous, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation.
Blurred vision, convulsions, insomnia.
Eye Disorders
Eye irritation, reversible loss of color vision, visual disturbances.
Ear and Labyrinth Disorders
Ear pain, tinnitus, vertigo.
Cardiac / Vascular Disorders
Edema, hypertension and cardiac failure have been reported in association with NSAID treatment.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke),Palpitations, Hypotension.
Respiratory, Thoracic and Mediastinal Disorders
Asthma, dyspnea.
Gastrointestinal Disorders
The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed.
Elderly or debilitated patients seem to tolerate gastrointestinal ulceration or bleeding less well than other individuals and most spontaneous reports of fatal GI events are in this population.
Anorexia, colitis, enterocolitis, gastric ulceration with or without hemorrhage, pancreatitis, steatorrhea.
Hepato-Bilary Disorders
Borderline elevations of one or more liver function tests, cholestasis jaundice. Mild hepatotoxicity, hepatitis, hepatorenal syndrome.
Skin and Subcutaneous Tissue Disorders
Angioedema, laryngeal edema, erythema multiform, face edema, bullous reactions including Lyell's syndrome (toxic epidermal necrolysis) and Stevens-Johnson syndrome, perspiration, rash, photosensitivity reaction, pruritus and urticaria.
Renal and Urinary Disorders
Allergic glomerulonephritis, acute interstitial nephritis, dysuria, hematuria, nephrotic syndrome, non-oliguric renal failure (particularly in dehydration), proteinuria, renal failure including renal papillary necrosis.
General Disorders
Fatigue, malaise, multi-organ failure, pyrexia.
Investigations
A positive reaction in certain tests for bile in the urine of patients receiving Mefenamic acid has been demonstrated to be due to the presence of the drug and its metabolites and not to the presence of bile.
Dicyclomine Hydrochloride
Most adverse reactions reported in clinical trials conducted with Dicyclomine were typically anticholinergic in nature such as dry mouth, dizziness, blurred vision, nausea, light-headedness, drowsiness, weakness, and nervousness.
Other adverse reactions reported with Dicyclomine and pharmacologically similar drugs, e.g., other anti-cholinergic and antispasmodics were:
Gastrointestinal: Vomiting, constipation, bloated feeling, abdominal pain, taste loss, anorexia may occur.
Central Nervous System: Tingling, headache, numbness, mental confusion and/or excitement (especially in elderly persons), dyskinesia, lethargy, syncope, speech disturbance, insomnia have been reported.
Ophthalmologic: Diplopia, mydriasis, cycloplegia, increased ocular tension.
Dermatologic/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.
OVERDOSE
Mefenamic Acid
It is important that the recommended dose is not exceeded, and the regime adhered to since some reports have involved daily dosages under 3g.
Symptoms
Symptoms include headache, nausea, vomiting Epigastric pain, gastrointestinal bleeding, rarely diarrhea, disorientation, excitation, coma, drowsiness, tinnitus, fainting, occasionally and convulsions [Mefenamic acid has a tendency to induce tonic-clonic (grand mal) convulsions in overdose. In cases of significant poisoning acute renal failure and liver damage are possible.
Management
Patients should be treated symptomatically as required. Within one hour of ingestion of a potentially toxic amount activated charcoal should be considered. Alternatively, in adults gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose. Good urine output should be ensured. Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient's clinical condition. Hemodialysis is of little value since Mefenamic acid and its metabolites are firmly bound to plasma proteins.
Dicyclomine Hydrochloride
Symptoms: Symptoms of Dicyclomine overdose 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 (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).
Treatment: Treatment should consist of gastric lavage, emetics, and activated charcoal. It is not known whether Dicyclomine is dialyzable. Sedatives (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.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamics Properties
Mefenamic Acid
Mefenamic acid belongs to the NSAID category which exhibit anti-inflammatory, analgesic, and antipyretic activities. The mechanism of action of Mefenamic acid is related to prostaglandin inhibition. Prostaglandins are implicated in a number of disease processes including inflammation, modulation of the pain response, dysmenorrhea, menorrhagia, and pyrexia. Like all other NSAIDs, Mefenamic acid inhibits the enzyme cyclooxygenase (COX) which is responsible for formation of prostaglandins. This results in a reduction in the rate of prostaglandin synthesis and reduced prostaglandin levels. Additionally, Mefenamic acid also blocks the prostaglandin receptors to prevent the effects of preformed prostaglandins. i.e., it inhibits binding of PGE2 to its receptors. Mefenamic acid therefore inhibits both, the synthesis and response to prostaglandins. Mefenamic acid has analgesic and antipyretic properties acting by both central and peripheral mechanisms. This dual site, double blockade mode of action of Mefenamic acid is important in its clinical efficacy.
Dicyclomine Hydrochloride
Dicyclomine is an anti-spasmodic and anti-muscarinic agent. Dicyclomine relieves smooth muscle spasm of the GI, biliary and ureteric tracts. This action of Dicyclomine is achieved via a dual mechanism:
Pharmacokinetic Properties
Mefenamic Acid
Mefenamic acid is rapidly absorbed after oral administration. Peak plasma levels are attained in
2 to 4 hours. More than 90% of Mefenamic acid is bound to plasma proteins, mainly albumin.
Mefenamic acid is metabolized by cytochrome P450 enzyme [CYP2C9] to 3-hydroxymethyl Mefenamic acid. Approximately 52% of a Mefenamic acid dose is excreted into the urine and up to 20% of the dose is excreted by fecal route. The elimination half-life of Mefenamic acid is approximately 2 hours. Because both renal and hepatic excretions are significant pathways of elimination, dosage adjustments in patients with renal or hepatic dysfunction may be necessary.
Dicyclomine Hydrochloride
Dicyclomine is rapidly absorbed after oral administration, reaching peak values within 60 to 90 minutes. Mean volume of distribution following a 20 mg oral dose is approximately 3.65 l/kg, suggesting extensive distribution in tissues. The metabolism of Dicyclomine was not studied. The principal route of excretion 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.
Special Precautions for Storage
Store in the original package. Store protected from light and moisture at a temperature not exceeding 30°C. Keep out of reach of children.