1.
Composition
Paracetamol 125mg
Mefenamic acid 50mg
2. Dosage form and strength
Centamol Plus suspension is available bottle of 60ml with a measuring cup.
3. Clinical particulars
3.1 Therapeutic indication
Centamol Plus suspension is licensed for treatment of pain and fever in children.
3.2 Posology and method of administration
The usual recommended oral dose of Centamol Plus in children is as under:
• 6 months-2 years age: 1 table spoonful three times a day.
• 2-5 years age: 1- 2 table spoonful three times a day.
3.3 Contraindication
The use of Centamol Plus suspension is contraindicated in patients with:
• Hypersensitivity to any of the ingredients of the formulation.
• Patients with severe hepatic dysfunction
3.4 Special warnings and precautions for use
• In case a hypersensitivity reaction occurs which is rare, Centamol Plus suspension
should be discontinued.
• Centamol Plus suspension contains Paracetamol and therefore should not be
used in conjunction with other Paracetamol containing products.
• Centamol Plus suspension should be used with caution in patients with renal or
hepatic dysfunction, diabetes mellitus, hyperthyroidism, cardiovascular
problems, epilepsy and closed angle glaucoma.
• Chronic heavy alcohol abusers may be at increased risk of liver toxicity from
excessive paracetamol use, although reports of this event are rare. These reports
usually involve cases of severe chronic alcoholics and dosages of paracetamol
that most often exceed recommended doses. Chronic alcoholics should not
exceed 2 g/day of paracetamol.
3.5 Drug interactions
Paracetamol
• Anticoagulant drugs (warfarin) - dosage may require reduction if paracetamol
and anticoagulants are taken for a prolonged period of time
• Paracetamol absorption is increased by substances that increase gastric
emptying, e.g. metoclopramide
• Paracetamol absorption is decreased by substances that decrease gastric
emptying, e.g. propantheline, antidepressants with anticholinergic properties,
and narcotic analgesics
• Paracetamol may increase chloramphenicol concentrations
• The risk of paracetamol toxicity may be increased in patients receiving other
potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes
such as alcohol and anticonvulsant agents
• Paracetamol excretion may be affected and plasma concentrations altered when
given with probenecid
• Cholestyramine reduces the absorption of paracetamol if given within 1 hour.
• Antivirals: Regular use of paracetamol possibly reduces metabolism of
Zidovudine (increased risk of neutropenia).
Mefenamic Acid
• Mefenamic Acid enhances activity of oral anticoagulants but rarely significant.
• Increased cyclosporine, lithium toxicity and convulsions reported with
ciprofloxacin.
• Absorption is increased by Magnesium Hydroxide antacids.
3.6 Use in special population
Pediatric: Centamol Plus suspension is safe in children.
Geriatric: Elderly population may be at greater risk for the side-effects.
Liver impairment: Use with caution.
Renal failure: Use with caution.
Pregnancy and lactation: Centamol Plus suspension is not recommended for
Women who are in their late stages of pregnancy. Since Mefenamic acid is
distributed into breast milk, use in lactating mothers should be avoided.
3.7 Effects on ability to drive and use machine
Patients should be cautioned against engaging in activities requiring complete mental
alertness, and motor coordination such as operating machinery until their response to
Centamol Plus Suspension is known.
3.8 Undesirable effects
The most commonly reported adverse effects are feeling or being sick, hypersensitivity
reactions, skin rashes, diarrhoea, nausea.
3.9 Overdose
There is limited experience of overdose with Centamol plus Suspension. Initiate general
symptomatic and supportive measures in all cases of overdosages where necessary.
4. Pharmacological properties
4.1 Mechanism of action
Paracetamol act primarily in the CNS, increasing the pain threshold by inhibiting both
isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin
(PG) synthesis. The antipyretic properties of acetaminophen are likely due to direct effects
on the heat-regulating centres of the hypothalamus resulting in peripheral vasodilation,
sweating and hence heat dissipation.
Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting
the action of prostaglandin synthetase. As these receptors have a role as a major mediator
of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the
symptoms of pain are temporarily reduced.
4.2 Pharmacodynamic properties
Paracetamol is a widely used analgesic and antipyretic drug that is used for the relief of
fever, headaches, and other minor aches and pains. It is a major ingredient in numerous
cold and flu medications and many prescription analgesics. It is extremely safe in standard
doses, but because of its wide availability, deliberate or accidental overdoses are not
uncommon. Paracetamol, unlike other common analgesics such as aspirin and ibuprofen,
has no anti-inflammatory properties or effects on platelet function, and it is not a member
of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. At
therapeutic doses Paracetamol does not irritate the lining of the stomach nor affect blood
coagulation, kidney function, or the fetal ductus arteriosus (as NSAIDs can). Like NSAIDs and
unlike opioid analgesics, Paracetamol does not cause euphoria or alter mood in any way.
Paracetamol and NSAIDs have the benefit of being completely free of problems with
addiction, dependence, tolerance and withdrawal. Paracetamol is used on its own or in
combination with pseudoephedrine, dextromethorphan, chlorpheniramine,
diphenhydramine, doxylamine, codeine, hydrocodone, or oxycodone.
Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of
nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and
antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin
synthetase.
4.3 Pharmacokinetic properties
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma
concentrations occurring about 10 to 60 minutes after oral doses. Paracetamol is distributed
into most body tissues. It crosses the placenta and is present in breast milk. Plasma-protein
binding is negligible 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 mainly in the liver and excreted in the urine mainly as the
glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol. A
minor hydroxylated metabolite (Nacetyl-p-benzoquinoneimine), is usually produced in very
small amounts by cytochrome P450 isoenzymes (mainly CYP2E1 and CYP3A4) in the liver
and kidney. It is usually detoxified by conjugation with glutathione but may accumulate
after paracetamol over dosage and cause tissue damage.
Mefenamic acid is absorbed from the gastrointestinal tract. Peak plasma concentrations
occur about 2 to 4 hours after ingestion. The plasma elimination half-life is reported to be
about 2 to 4 hours. Mefenamic acid is more than 90% bound to plasma proteins. It is
distributed into breast milk. Mefenamic acid is metabolised by the cytochrome P450
isoenzyme CYP2C9 to 3-hydroxymethyl Mefenamic acid, which may then be oxidised to 3-
carboxymefenamic acid. Over 50% of a dose may be recovered in the urine, as unchanged
drug or, mainly, as conjugates of Mefenamic acid and its metabolites.
5. Nonclinical properties
5.1 Animal Toxicology or Pharmacology
Not required.
6. Description
Already mentioned and covered in the above points.
7. Pharmaceutical particulars
7.1 Incompatibilities
There are no known incompatibilities.
7.2 Shelf-life
24 months.
7.3 Storage and handling instructions
Store below 25°C. Protect from light
