SQUARE PHARMACEUTICALS LTD.
PARACETAMOL + TRAMADOL HYDROCHLORIDE
This is indicated for the short-term (five days or less) management of acute pain.
Non-steroidal Anti-inflammatory Drugs (NSAIDs)
Tramadol, a centrally-acting analgesic, exists as a racemic mixture of the trans isomer, with important differences in binding, activity, and metabolism associated with the two enantiomers. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to 8-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to 8-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in 8-opioid binding. Opiate antagonist naloxone only partially antagonized tramadol-induced analgesia. Paracetamol (Acetaminophen) is thought to 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. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. While aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site, studies have found that acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. 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.
For the management of pain, the recommended dose is 1 or 2 tablets every 4 to 6 hours as needed for pain relief up to a maximum of 8 tablets per day. The dosing interval should not be less than six hours. This is not recommended in patients under 18 years of age.
Hypersensitivity to Tramadol Hydrochloride, paracetamol or to any of the excipients of the medicinal product. Acute intoxication with alcohol, hypnotic drugs, centrally-acting analgesics, opioids or psychotropic drugs. Should not be administered to patients who are receiving monoamine oxidase inhibitors or within two weeks of their withdrawal. Severe hepatic impairment. Epilepsy not controlled by treatment.
The most commonly reported undesirable effects during the clinical trials performed with the Paracetamol/ Tramadol Hydrochloride combination were nausea, dizziness and somnolence.
Since it is a fixed combination of active ingredients including Tramadol Hydrochloride, it should not be used during pregnancy & lactation
Should be used with caution in opioid dependent patients, or in patients with cranial trauma, in patients prone to convulsive disorder, biliary tract disorders, in a state of shock, in an altered state of consciousness for unknown reasons, with problems affecting the respiratory center or the respiratory function, or with an increased intracranial pressure. Paracetamol in overdosage may cause hepatic toxicity in some patients. At therapeutic doses, Tramadol Hydrochloride has the potential to cause withdrawal symptoms. Rarely, cases of dependence and abuse have been reported.
Store in cool & dry place, away from children.