PYXFENAC PLUS Aceclofenac 100 mg & Paracetamol 500 mg Tablets
Composition :
Each film coated tablet contains :
Aceclofenac BP…………..100 mg
Paracetamol BP………….500 mg
Excipients………………….Q.S.
Colour : Sunset Yellow FCF & Titanium Dioxide BP
DESCRIPTION:
PYXFENAC PLUS Tablets contain a fixed does combination of aceclofenac which is a non-steroidal drug with anti-inflammatory, analgesic and antipyretic effects and paracetamol which has analgesic and antipyretic properties and weak anti-inflammatory activity. Aceclofenac is chemically designated as 2-(2,6-Dichloroan alino) phenylacetoxyacetic acid. It has a structural formula of C16F11,CL2N0, and a molecular, weight of 354.2. On the other hand, the chemical name for paracetamol is N-acetyl-p-aminophenol and it is also known as acetaminophen Paracetamol has a has a structural. 1 formula of C81-19NO2 and its molecular weight 151.2.
PHARMACODYNAMICS:
The mode of action of aceclofenac is largely based on the inhibition of prostaglandin synthesis. Aceclofenac has bean shown fo have potent anti-inflammatory, analgesic, and antipyretic properties. On the other hand paracetamol produces analgesia by elevation of the pain threshold and antipyresis through action on the hypothaiamic heat-regulation centre.
In cases of acute pain, the use of two analgesics with different mechanisms of action i.e. aceciofenac acting on the inflamed tissues peripherally and paracetamol acting centrally has been shown to be synergistic The combination of aceclofenac and paracetamol provides rapid and strong initial analgesia because of simultaneous onset of analgesic action of both the drugs and a more prolonged analgesic effect due to the long lasting action of aceclofenac. Fixed dose combination of aceclofenac and paracetamol also improves patient compliance and tolerability.
PHARMACOKINETICS:
After oral administration, Aceclofenac is rapidly absorbed and the bioavailability is almost 100%. Peak plasma concentrations (Cmax) of approximately 8.25 mcg/ml are reached within 2 hours (Tmax) following ingestion. Aceclofenac is highly protein-bound (>99.7%). Aceclofenac penetrates into the synovial fluid, where the concentrations reach approximately 60% of those in plasma. The volume of distribution is approximately 30L. Aceclofenac is metabolized into active metabolites in hepatocytes and microsomes. The mean plasma elimination half-life is 4 -4.3 hours. Aceclofenac circulates mainly as unchanged drug. 4’hydroxyaceclofenac is the main metabolite of aceclofenac. It is also metabolized to a number of other metabolites including 5′. hydroxyaceclofenac, diclofenac, and 4′-hydroxydiclofenac and 5′- hydroxydiclofenac, Approximately two-thirds of the administered dose is excreted via the urine, mainly as hydroxy metabolites.
On the other hand, paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 1 0 to 60 minutes after oral administration. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk.
Plasma protein binding is negiigible at usual therapeutic concentrations but increases with increasing concentrations. The elimination half-life of paracetamol varies from about 1 to 3 hours. Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol A minor hydroxylated metabolite (N-acetyl-pbenzoquinoneimine) which is usually produced in Very small amounts by mixed-function oxidases in the liver and kidney and which is usually detoxified by conjugation with glutathione may accumulate following paracetamol overdosage and cause tissue damage.
INDICATIONS:
PYXFENAC PLUS is indicated for acute painful condition in adults only.
CONTRAINDICATIONS:
PYXFENAC PLUS is contraindicated in the following situations:
- Patients previously sensitive to aceclofenac or paracetamol or to to any of the excipients of the product.
- Patients in whom substances with a similar action (e.g. aspirin, or other NSAIDs), precipitate attacks of asthma, bronchospasm, acute rhinitis or urticaria or patients hypersensitive to these drugs.
- Patients with active or suspected peptic or duodenal ulcer or history of recurrent peptic or duodenal ulcer or who have gastrointestinal bleeding or other active bleedings or bleeding disorders.
- Patients with severe heart failure or severely impaired hepatic or renal function
- Pregnancy and lactation.
- For self-medication of pain for longer than 10 days unless directed by a physician, since pain of such intensity and duration may indicate a pathologic condition requiring medical evaluation and supervised treatment.
- For self-medication of marked fever (greater than 3950C), fever persisting longer than 3 days, or recurrent fever, unless directed by a physician, since such fevers may indicate serious illness requiring prompt medical evaluation
PRECAUTIONS AND WARNINGS:
Aceclofenac should be administered with caution and under close medical surveillance to patients suffering from gastro-intestinal disease and to those with a history of peptic ulceration, cerebrovascular bleeding, ulcerative colitis, Crohn’s disease, SLE, porphyria, haematopoietic- or coagulation disorders.
Caution should be exerciser in patients with mild to moderate impairment of hepatic, renal or cardiac function as well as in patients with other conditions predisposing to fluid retention. In these patients, 1he use of NSAIDs may result in deterioration of renal function and fluid retention Caution is also required in patients with diuretic treatment or otherwise at risk of hypovolemia.
Caution should be exercised in the treatment of elderly patients, who are generally more prone to adverse reactions. The consequences, e.g. gastrointestinal bleeding and/or perforation, are often more serious and may occur without warning symptoms or previous history, at any time during treatment. Elderly patients are more likely to be suffering from impaired renal, cardiovascular or hepatic function.
Patients who experience dizziness or other central nervous system disturbances while taking NSAI Ds should refrain from driving or operating machinery.
All patients who are receiving long-term treatment with NSAID should be monitored as a precautionary measure (e.g renal hepatic function and blood counts).
Paracetamol should be given with care to patients with impaired kidney or liver function. It should also be given with care to patients with alcohol dependence and to patients taking other drugs that affect the liver.
DRUG INTERACTIONS:
Lithium and methotrexate:
Aceclofenac, like many other NSAIDs, may increase the plasma concentrations of lithium and methotrexate by inhibiting their tubular secretion and renal clearance.
Diuretics:
Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics. When concomitant administration with potassium sparing diuretics is employed, serum potassium should be monitored.
Anticoagulants:
Like other NSAIDs, aceclofenac may enhance the activity of anticoagulants. Close monitoring of patients on combined anticoagulantand aceclofenac therapy should be undertaken.
Antidiabetic agents:
There are reports from marketing experiences of changes in the effects of insulin or of hypoglycemic agents in the presence of NSAIDs. The likelihood of such an interaction is probably low with most commonly used NSAIDs but increased glucose monitoring for a short period of time is indicated.
Digoxin:
Caution should be exercised if aceclofenac, like other NSAIDs, is administered concomitantly with digoxin due to an increased risk of digoxin toxicity.
Other NSAIDs and corticosteroids:
Concomitant therapy with aspirin, other NSAIDs and corticosteroids may increase the frequency of side effects.
Cyclosporine:
Cyclosporine nephrotoxicity may be increased by the effect of NSAIDs on renal prostaglandins.
Quinolone antimicrobials:
Convulsions may occur due to interaction between quinolones and NSAIDs. Therefore, caution should be exercised when considering the use of quinolone in patients who are already receiving a NSAID.
The risk of paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes. The absorption of paracetamol may be accelerated by drugs such as metoclopramide. Excretion may be affected anq plasma concentrations altered when administered with probenecid. Cholestyramine reduces the absorption of paracetamol if given within one hour of paracetamol administration.
USAGE IN PREGNANCY, LACTATION AND CHILDREN:
There is no information on the use of aceclofenac during pregnancy. The regular use of NSAI Ds during the last trimester of pregnancy may increase uterine tone and contraction. NSAID use may also result in premature closure of the fetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of the newborn, delay onset and increase duration of labour. It is not known whether aceclofenac is excreted in human milk. Therefore, aceclofenac should not be given during pregnancy and lactation unless potential benefits to the mother out weigh the possible risks to the fetus. There are no clinical data on the use of aceclofenac in children.
ADVERSE EFFECTS:
The majority of side effects reported with aceclofenac therapy are gastrointestinal (dyspepsia. abdominal pain, nausea and diarrhoea). Most frequent are dyspepsia (7.5%) and abdominal pain (6.2%). Other reported side effects include the following:
General:
Dizziness
Gastrointestinal system disorders:
Flatulence, gastritis, constipation, vomiting, ulcerative stomatitis
Liver and biliary:
Increased hepatic enzymes Skin and appendages: Pruritus, rash, dermatitis Metabolic and nutritional: Urea increased, serum creatinine increased side-effects of paracetamol are rare and usually mild, although haematological reactions including thrombocytopenia, leucopenia, pancytopenia, neutropenia, and agramllocytosis have been reported. Skin rashes, and other hypersensitivity reactions occur occasionally.
OVERDOSE:
There are no human data available on the consequences of aceclofenac overdosage. The symptoms could be nausea, vomiting, stomach pain, dizziness, somnolence afld headache. Overdosage with paracetamol results in pallor, nausea, vomiting, anorexia and abdominal pain. It can result in severe liver damage and sometimes acute renal tubular necrosis. Treatment: Prompt treatment is essential in the management of paracetamol overdosage, this includes gastric iavage and treatment with acetylcysteine or methionine given intravenously or orally. Supportive and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastrointestinal irritation and respiratory depression.
DOSAGE &ADMINISTRATION:
Tablets are supplied for oral administration and should be swalio ed whole with a sufficient quantity of liquid. They can be taken with food.
Adults:
The maximum recommended dose is one tablet twice daily, taken as one tablet in the morning and evening.
Elderly:
Generally, no dose reduction is necessary, however, consider the precautions as mentioned above.
Children:
The safety and efficacy of the drug in children and adolescents has not been established. Hepatic insufficiency PYXFENAC PLUS Tablets should not be used in patients with hepatic insufficiency due to the increased risk of hepatotoxicity in such patients.
Renal insufficiency:
PYXFENAC PLUS Tablets should be used with extreme caution in patients with renal insuffciency due to the Increased risk of toxicity in such patients.
Dosage :
As directed by the physician.
Storage :
Store below 30°C. Protect from light and moisture. Keep the medicine out of reach of children.
Presentation:
20 Tablets
Marketed by:
PYXUS PHARMACEUTICALS PVT. LTD.
