Lotram Plus

Each film-coated tablet contains: Paracetamol BP 325 mg, Tramadol Hydrochloride BP 37.5 mg.

Analgesic.
Pharmacology: Tramadol Hydrochloride: Tramadol Hydrochloride is a centrally acting analgesic. It is a non selective pure agonist at mu, delta and kappa opioid receptors with a higher affinity for the receptor. Other mechanisms which may contribute to its analgesic effect are inhibition of neuronial 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 sensitize 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.
Pharmacokinetics: Tramadol: 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 breastmilk. The elimination half-life is about 6 hours.
Paracetamol: 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-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 overdosage and cause tissue damage.

Indicated for the symptomatic treatment of moderate to severe pain.

Adult and children > 16 years of age: An initial dose of two tablets is recommended.
Maximum single dose: 1-2 tablets every 4-6 hours as needed for each pain relief up to a maximum of 8 tablets a day.
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.

Hypersensitivity to the active substances or to any of the excipients. It is also contraindicated in cases of acute intoxication with alcohol, hypnotics, narcotics, centrally-acting analgesics, opioids or psychotic drugs.

Seizures: Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing report indicate that seizure risk is increased with doses of tramadol above the recommended range. Concomitant use of tramadol increases the seizure risk in patients taking Selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), tricyclic antidepressants (TCAs), and other tricyclic compounds (eg, cyclobenzaprine, promethazine, etc.), or opioids.
Administration of tramadol may enhance the seizure risk in patients taking MAO inhibitors, neuroleptics or other drugs that reduce the seizure threshold.
Risk of convulsions may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (eg. head trauma, metabolic disorders, alcohol and drug withdrawal, Central Nervous System (CNS) infections). In tramadol overdose, naloxone administration may increase the risk of seizure.
Anaphylactoid reactions: Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive Paracetamol + Tramadol.
Respiratory Depression: Administer the drug cautiously in patients at risk for respiratory depression. When large doses of tramadol are administered with anesthetic medications or alcohol, respiratory depression may result. Treat such cases as an overdose. If naloxone is to be administered, use cautiously because it may precipitate seizures.
Use with CNS Depressants: It should be used with caution and in reduced dosages when administered to patients receiving CNS depressants eg, alcohol, opioids, anesthetic agents, phenothiazines, tranquilizers or sedative hypnotics.
Increased intracranial pressure or head trauma: It should be used with caution in patients with increased intracranial pressure or head injury.
Use in Opioid-Dependent Patients: It should not be used in opioid-dependent patients. Tramadol has been shown to re-initiate physical dependence in some patients that have been previously dependent on other opioids.
Used with Alcohol: Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive paracetamol use.
Withdrawal: Withdrawal symptoms may occur if the product is discontinued abruptly. Panic attacks, severe anxiety, hallucinations, paresthesia, tinnitus and unusual CNS symptoms have also been rarely reported with abrupt discontinuation of Tramadol HCl. Clinical experience suggests that withdrawal symptoms may be relieved by tapering the medication.
Use with MAO Inhibitors and Serotonin Reuptake Inhibitors: Use the Paracetamol + Tramadol HCl with great caution in patients taking monoamine oxidase inhibitors. Concomitant use of tramadol with MAO inhibitors or SSRIs increase the risk of adverse events, including seizure and serotonin syndrome.
Use in Renal Disease: It has not been studied in patients with impaired renal function. In patients with creatinine clearances of <30 mL/min, it is recommended that the dosing interval be increased not to exceed 2 tablets every 12 hrs.
Use in Hepatic Disease: The use of the product in patients with severe hepatic impairment is not recommended.
General: The recommended dose should not be exceeded. It should not be co-administered with other tramadol or paracetamol-containing products.
Effects on the Ability to Drive or Operate Machinery: It may impair mental and physical abilities required for the performance of potentially hazardous tasks eg, driving a car or operating machinery.

Tramadol has been shown to cross the placenta. There are no adequate and well-controlled studies in pregnant women. Safe use in pregnancy has not been established.
It is not recommended for nursing mothers because its safety in infants and newborns has not been studied.

The most frequently reported events were in the central nervous system and gastrointestinal system.
The most common report events were nausea, dizziness and somnolence.
In addition, the following effects have been frequently observed, through the frequency is generally lower: Body as a Whole: Asthenia, fatigue, hot flushes.
Central and Peripheral Nervous System: Headache, tremor.
Gastrointestinal System: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, dry mouth, vomiting.
Psychiatric Disorders: Anorexia, anxiety, confusion, euphoria, insomnia, nervousness.
Skin and Appendages: Pruritus, rash, increased sweating.
Uncommon reported clinically significant adverse experiences with at least a possible causal link to tramadol + paracetamol include: Body as a Whole: Chest pain, rigors, syncope, withdrawal syndrome.
Cardiovascular Disorders: Hypertension, aggravated hypertension, hypotension.
Central and Peripheral Nervous System: Ataxia, convulsions, hypertonia, migraine, aggravated migraine, involuntarily muscle contractions, paresthesia, stupor, vertigo.
Gastrointestinal System: Dysphagia, melena, tongue edema.
Hearing and Vestibular Disorders: Tinnitus.
Heart Rate and Rhythm Disorders: Arrythmia, palpitation, tachycardia.
Liver and Biliary System: Liver test abnormalities.
Metabolic and Nutritional Disorders: Decreased weight.
Psychiatric Disorder: Amnesia, depersonalization, depression, drug abuse, emotional lability, hallucination, impotence, bad dreams, abnormal thinking.
Red Blood Cell Disorders: Anemia.
Respiratory System: Dyspnea.
Urinary System: Albuminuria, micturition disorder, oliguria, urinary retention.
Vision Disorders: Abnormal vision.
Other Clinically Significant Adverse Experiences Previously Reported in Clinical Trials or Post-Marketing Reports With Tramadol HCl: Other events which have been reported with the use of tramadol products include: Orthostatic hypotension, hypotension, allergic reactions (including anaphylaxis and urticaria, Stevens-Johnson syndrome/TENS), cognitive dysfunction, suicidal tendency and hepatitis.
Reported laboratory abnormalities include elevated creatinine. Serotonin syndrome (whose symptoms may include fever, excitation, shivering and agitation) has been reported with tramadol when used concomitantly with other serotonergic agents, SSRIs and MAO inhibitors. Post-marketing surveillance of tramadol has revealed rare alterations of warfarin effect, including elevation of prothrombin times.
Other Clinically Significant Adverse Experiences Previously Reported in Clinical Trials or Post-Marketing Reports with Paracetamol: Allergic reactions (primarily skin rash) or report of hypersensitivity secondary to paracetamol are rare and generally controlled by discontinuation.

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