RiteMED Tramadol HCl + Paracetamol

Tramadol hydrochloride, paracetamol.

Yellow coloured, elongated, biconvex film-coated tablet scored on one side.
Each film-coated tablet contains: Tramadol Hydrochloride, BP 37.5 mg, Paracetamol, BP 325 mg.

Opioid Analgesics/Non-Opioid Analgesics/Antipyretic.
Pharmacology: Tramadol hydrochloride: It is a centrally acting analgesic. It is a non selective pure agonist at μ, δ, and κ opioid receptors with a higher affinity for the μ receptor. Other mechanisms which may contribute to its analgesic effect are inhibition of neuronal reuptake of noradrenaline and enhancement of serotonin release.
Paracetamol: The mechanism of analgesic action has not been fully determined.
Paracetamol may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent, through a peripheral action by blocking pain-impulse generation.
The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation.
Paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat-regulation center to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.
Pharmacodynamics: Analgesics: Tramadol is an opioid analgesic that acts on the central nervous system. Tramadol is pure non selective agonists of the μ, δ, and κ opioid receptors with a higher affinity for the µ receptors. Other mechanisms which contribute to its analgesic effect are inhibition of neuronal reuptake of noradrenaline and enhancement of serotonin release. Tramadol has an antitussive effect. Unlike morphine, a broad range of analgesic doses of Tramadol has no respiratory depressant effect. Similarly, the gastrointestinal motility is not modified. The cardiovascular effects are generally slight. The potency of Tramadol is considered to be one-tenth to one-sixth that of morphine.
Mechanism of Action: The precise mechanism of the analgesic properties of Paracetamol is unknown and may involve central and peripheral effects.
Tramadol hydrochloride/Paracetamol is positioned as a step II analgesic in the WHO pain ladder and should be utilised accordingly by the physician.
Pharmacokinetics: Tramadol is readily absorbed after oral doses but is subject to some first-pass metabolism. Mean absolute bioavailability is about 70 to 75% after oral use and 100% after intramuscular injection.
Plasma protein binding is about 20%. Tramadol is metabolised by N- and O-demethylation via the cytochrome P450 isoenzymes CYP3A4 and CYP2D6 and glucuronidation or sulfation in the liver. The metabolite O-desmethyltramadol is pharmacologically active. Tramadol is excreted mainly in the urine, predominantly as metabolites. Tramadol is widely distributed, crosses the placenta, and appears in small amounts in breast milk. The elimination half-life is about 6 hours.
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 (N-acetyl-p-benzoquinone imine), 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 overdosage and cause tissue damage.

Indicated for the symptomatic treatment of moderate to severe pain.
Paracetamol is used for mild to moderate pain and for fever.
Tramadol is used for moderate to severe pain.

Adults: An initial dose of two tablets is recommended.
Additional doses can be taken as needed, not exceeding 8 tablets per day.
The dosing interval should not be less than six hours.
Children: The effective and safe use has not been established in children below the age of 12 years.
Treatment is therefore not recommended in this population.
Or as prescribed by the physician.

Tramadol hydrochloride/Paracetamol is a fixed combination of active ingredients. In case of overdose, the symptoms may include the signs and symptoms of toxicity of Tramadol or Paracetamol or of both these active ingredients.
Symptoms of Overdose from Tramadol: In principle, on intoxication with tramadol, symptoms similar to those of other centrally acting analgesics (opioids) are to be expected. These include in particular, miosis, vomiting, cardiovascular collapse, consciousness disorders up to coma, convulsions and respiratory depression up to respiratory arrest.
Symptoms of Overdose from Paracetamol: An overdose is of particular concern in young children. Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain.
Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Liver damage is possible in adults who have taken 7.5-10 g or more of Paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.
Emergency treatment: Transfer immediately to a specialised unit.
Maintain respiratory and circulatory functions.
Prior to starting treatment, a blood sample should be taken as soon as possible after overdose in order to measure the plasma concentration of Paracetamol and Tramadol and in order to perform hepatic tests.
Perform hepatic tests at the start (of overdose) and repeat every 24 hours. An increase in hepatic enzymes (ASAT, ALAT) is usually observed, which normalizes after one or two weeks.
Empty the stomach by causing the patient to vomit (when the patient is conscious) by irritation or gastric lavage.
Supportive measures such as maintaining the patency of the airway and maintaining cardiovascular function should be instituted; naloxone should be used to reverse respiratory depression; fits can be controlled with diazepam.
Tramadol is minimally eliminated from the serum by haemodialysis or haemofiltration. Therefore, treatment of acute intoxication with Tramadol hydrochloride/Paracetamol with haemodialysis or haemofiltration alone is not suitable for detoxification.
Immediate treatment is essential in the management of Paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any adult or adolescent who had ingested around 7.5 g or more of Paracetamol in the preceding 4 hours or any child who has ingested ≥150 mg/kg of Paracetamol in the preceding 4 hours should undergo gastric lavage. Paracetamol concentrations in blood should be measured later than 4 hours after overdose in order to be able to assess the risk of developing liver damage (via the Paracetamol overdose nomogram). Administration of oral methionine or intravenous N-acetylcysteine (NAC) which may have a beneficial effect up to at least 48 hours after the overdose, may be required. Administration of intravenous N-acetylcysteine (NAC) is most beneficial when initiated within 8 hours of overdose ingestion. However, NAC should still be given if the time to presentation is greater than 8 hours after overdose and continued for a full course of therapy. NAC treatment should be started immediately when massive overdose is suspected. General supportive measures must be available.
Irrespective of the reported quantity of Paracetamol ingested, the antidote for Paracetamol, NAC, should be administered orally or intravenously, as quickly as possible, if possible, within 8 hours following the overdose.

Hypersensitivity to the active substance or to any of the excipients.

The maximum dose of 8 tablets of Tramadol hydrochloride/Paracetamol should not be exceeded in adults and adolescents 12 years and older. In order to avoid inadvertent overdose, patients should be advised not to exceed the recommended dose and not to use any other Paracetamol (including over-the-counter) or Tramadol hydrochloride containing products concurrently without the advice of a physician.
In severe renal impairment (creatinine clearance <10 mL/min), Tramadol hydrochloride/Paracetamol is not recommended.
In patients with severe hepatic impairment, Tramadol hydrochloride/Paracetamol should not be used. The hazards of Paracetamol overdose are greater in patients with non-cirrhotic alcoholic liver disease. In moderate cases, prolongation of dosage interval should be carefully considered.
In severe respiratory impairment, Tramadol hydrochloride/Paracetamol is not recommended.
Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, Tramadol cannot suppress morphine withdrawal symptoms.
Convulsions have been reported in Tramadol-treated patients susceptible to seizures or taking other medications that lower the seizure threshold, especially selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local anaesthesia. Epileptic patients controlled by a treatment or patients susceptible to seizures should be treated with Tramadol hydrochloride/Paracetamol only if there are compelling circumstances. Convulsions have been reported in patients receiving Tramadol at the recommended dose levels. The risk may be increased when doses of Tramadol exceed the recommended upper dose limit.

Tramadol should be used with caution in patients with renal or hepatic impairment and should be avoided if renal impairment is severe. Removal by haemodialysis is reported to be minimal at 7%.
Tramadol should be used with care in patients with a history of epilepsy or those susceptible to seizures.
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.

Pregnancy: It should not be used during pregnancy.
Lactation: It is a fixed combination of active ingredients including Tramadol. It should not be ingested during breast feeding. Tramadol and its metabolites are found in small amounts in human breast milk. An infant could ingest about 0.1% of the dose given to the mother.

Tramadol may produce fewer typical opioid adverse effects such as respiratory depression and constipation. In addition to hypotension, hypertension has occasionally occurred.
Adverse effects of Paracetamol are rare and usually mild, although haematological reactions including thrombocytopenia, leucopenia, pancytopenia, neutropenia, and agranulocytosis have been reported. Skin rashes and other hypersensitivity reactions occur occasionally.

Carbamazepine is reported to diminish the analgesic activity of Tramadol by reducing serum concentrations. The risk of seizures is increased if Tramadol is used with other drugs that have the potential to lower the seizure threshold. Tramadol inhibits reuptake of noradrenaline and serotonin and enhances serotonin release and there is the possibility that it may interact with other drugs that enhance monoaminergic neurotransmission including lithium, tricyclic antidepressants, and SSRIs; it should not be given to patients receiving MAOIs or within 14 days of their discontinuation. Metabolism of Tramadol is mediated by the cytochrome P450 isoenzyme CYP2D6. Use with specific inhibitors of this enzyme, such as quinidine, may increase concentrations of Tramadol and lower concentrations of its active metabolite but the clinical consequences of this effect are unclear.
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 and plasma concentrations altered when given with probenecid. Colestyramine reduces the absorption of Paracetamol if given within 1 hour of Paracetamol.

Store at temperatures not exceeding 30°C.

Analgesics (Opioid)

N02AJ13 - tramadol and paracetamol ; Belongs to the class of opioids in combination with other non-opioid analgesics. Used to relieve pain.

Rx