Www.alembicpharmaceuticals.com



COMPOSITIONEach tablet containsParacetamol……………………………500 mgChlorpheniramine Maleate……………….2 mgPhenylephrine HCl………………………..10 mgExcipients……q.s.INDICATIONS AND USAGESymptomatic relief of common cold associated with nasal congestion, headache, mild pain, rhinorrhea and sneezing.Relief of nasal and sinus congestion. Relief of allergic symptoms of the nose or sinus due to upper respiratory tract allergies. Adjunct with antibacterials in sinusitis and otitis media associated with nasal congestion.DOSAGE AND ADMINISTRATIONAdults and children 12 years of age and older: one tablet thrice daily (every 8 hours).CONTRA-INDICATIONSContraindicated in documented hypersensitivity; asthma attacks, narrow-angle glaucoma, symptomatic prostate hypertrophy, bladder-neck obstruction, and stenosing peptic ulcer; known G-6-PD deficiencyChlorpheniramine may cause significant confusional symptoms; Use of MAO inhibitor within 14 daysParacetamol hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; contained in many OTC products and combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum doseWARNINGS & PRECAUTIONSCaution in elderly patients, hyperthyroidism, myocardial disease, bradycardia, partial heart block or severe arteriosclerosis when administering phenylephrine.Caution in asthma, bladder neck obstruction, cardiovascular disease, COPD, GI obstruction, glaucoma, hepatic impairment, hyperthyroidism, increased intraocular pressure, malnutrition, renal impairment, elderly patients, and patients taking CNS depressants.Caution in severe hypovolemia if taking paracetamol productsParacetamol: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rashIt is advisable not to drive or operate machinery when on treatment with wikoryl 10.SPECIAL POPULATIONSUse in special population: 1. Pediatric: Wikoryl 10 tablet should be used with caution in children and generally avoided in those less than 12 years of age. 2. Geriatric: Elderly population may be at greater risk for the side-effects. 3. Liver impairment: Use with caution. 4. Renal failure: Use with caution. 5. Pregnancy and lactation: US Food and Drug Administration (FDA) has specified Chlorpheniramine maleate as a pregnancy category B drug which indicates that animal and human studies have failed to demonstrate a risk to the fetus in any trimester. Paracetamol has been specified as a pregnancy category C drug which indicates that animal studies show an adverse effect on the fetus but there are no teratogenic studies of Paracetamol in pregnant women. Wikoryl 10 is recommended to be taken during pregnancy only under doctor's recommendationCLINICAL PHARMACOLOGYMechanism of actionAntihistaminic activity of chlorpheniramine relieves the symptoms of sneezing and runny nose by help dry up secretions and also have a sedative action. In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine H1-receptors, resulting in nasal pruritus, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine maleate binds to the histamine H1 receptor. This block the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamineParacetamol has both analgesic and anti-pyretic activity, which is believed to be mediated through inhibition of the cyclooxygenase (COX) pathway within the central nervous system. Although this mechanism is shared with the non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol does not have significant anti-inflammatory activity nor does it inhibit production of pro-clotting thromboxanes. Additional pathways such as the serotonergic descending pain pathways may be involved in the anti-nociceptive effect of paracetamol.Phenylephrine is a potent alpha1-adrenoceptor agonist. Its action on the peripheral alpha 1 receptors induces vasoconstriction, which in the nasal mucosa, reduces oedema and nasal swelling. PHARMACOKINETICSPhenylephrine hydrochloride and ParacetamolPhenylephrine has low oral bioavailability owing to irregular absorption and first-pass metabolism by monoamine oxidase in the gut and liver. When injected subcutaneously or intramuscularly it takes 10 to 15 minutes to act; subcutaneous and intramuscular injections are effective for up to about 1 hour and up to about 2 hours, respectively. Intravenous injections are effective for about 20 minutes. Systemic absorption follows topical application.Gastric emptying changes could affect paracetamol absorption. However, phenylephrine has no effect on gastric emptying (rat animal model). Additionally, no risk for transport protein interactions in the absorption site is expected as phenylephrine is not an evident substrate of transport proteins. After oral dosing, phenylephrine is rapidly absorbed in the GIT being highly conjugated by sulphation and glucuronidation during first pass. The majority of this phenylephrine metabolism takes place within the enterocytes.The minor hepatic metabolism occurs via MAO. The final systemic availability of active parent is ~1%. At therapeutic oral doses of 12.2 mg phenylephrine hydrochloride (parent) levels are systemically very low (<1 ng/mL) after first pass. In contrast, paracetamol metabolism is hepatic during and after first pass with bioavailability >75%. Competition for the sulphation/ glucuronidation path ways with paracetamol is not an issue as the phenylephrine is metabolized by enterocytes and paracetamol in the liver. The differentiation between metabolisms in enterocytes (phenylephrine) vs. the liver (paracetamol) mitigates the risk of shunting to the P450 (NAPQI) pathway for paracetamol. On the other hand, paracetamol is not known to saturate the pre-systemic sulphation or glucuronidation paths (being highly bioavailable) thus an effect of increased phenylephrine levels when concomitant paracetamol at therapeutic doses is also ruled out. At therapeutic doses, paracetamol protein binding is low (<5-24%). No clinically significant interactions based on plasma protein binding displacement have been identified to date. If displacement of bound paracetamol occurred by phenylephrine with concomitant increase of free paracetamol, as the drug’s elimination is not rate limited then paracetamol would eliminate faster and also compensate by distributing further and equilibrium would be re-established. Therefore, no interaction effects are foreseeable at drug distribution. Chlorpheniramine maleate It is absorbed relatively slowly from the gastrointestinal tract, with peak plasma concentrations occurring about 2.5 to 6 hours after oral administration. Chlorpheniramine appears to undergo considerable first-pass metabolism. Bioavailability is low, values of 25 to 50% having been reported. About 70% of chlorpheniramine in the circulation is bound to plasma proteins. There is wide inter-individual variation in the pharmacokinetics of chlorpheniramine; half-life values ranging from 2 to 43 hours have been reported. Chlorpheniramine is widely distributed in the body and enters the CNS. DRUG INTERACTIONSPhenylephrine:The co-administration of Monoamine Oxidase Inhibitors (MAOIs) or tricyclicantidepressants and an indirect or mixed-acting sympathomimetic may resultin a hypertensive crisis and hence such concomitant use is best avoided.Additionally sympathomimetics may reduce the efficacy of beta-blocking andanti-hypertensive drugs.Paracetamol:Anticoagulant drugs (warfarin) - dosage may require reduction if paracetamoland anticoagulants are taken for a prolonged period of timeParacetamol absorption is increased by substances that increase gastricemptying, e.g. metoclopramideParacetamol absorption is decreased by substances that decrease gastricemptying, e.g. antidepressants with anticholinergic properties, and narcoticanalgesicsParacetamol may increase chloramphenicol concentrationsThe risk of paracetamol toxicity may be increased in patients receiving otherhepatotoxic drugs or drugs that induce liver microsomal enzymes such asalcohol and anticonvulsant agentsParacetamol excretion may be affected when given with probenecidColestyramine reduces the absorption of paracetamol if given within 1 hour.Regular use of paracetamol possibly reduces metabolism of Zidovudine(increased risk of neutropenia).Adverse reactions – Wikoryl 10 tablt is well tolerated. Side effects are mild and often transient.WIKORYL 10 tablet is generally well tolerated and adverse events are rare.Hypersensitive individuals may display ephedrine-like reactions such as tachycardia,palpitations, headache, dizziness and nausea. Use of sympathomimetics has been associatedwith fear, anxiety, restlessness, tremor, weakness, dysuria, insomnia, hallucinations andconvulsions. Chlorpheniramine in WIKORYL 10 Tablet may cause sedation. ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download