Lornoxicam + Paracetamol + Tramadol

Usage

This combination medication is prescribed for the short-term management of moderate to severe acute pain, where the combined analgesic effects of the three components are warranted. It is not intended for chronic pain management. Due to the presence of tramadol, it’s typically reserved for cases where other pain management strategies have proven insufficient.

Pharmacological Classification: Analgesic (combining NSAID, non-opioid analgesic, and opioid analgesic mechanisms)

Mechanism of Action: This combination targets pain through multiple pathways:

• Lornoxicam: A non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, primarily COX-2, reducing prostaglandin synthesis, which are key mediators of inflammation and pain.
• Paracetamol (Acetaminophen): Acts centrally, likely inhibiting COX enzymes in the central nervous system and possibly affecting endocannabinoid pathways, thus influencing pain and fever perception.
• Tramadol: A weak opioid agonist that binds to mu-opioid receptors in the brain and spinal cord, modulating pain transmission. It also inhibits serotonin and norepinephrine reuptake, which contributes to its analgesic effect.

Alternate Names

There are no officially recognized alternate names for this specific combination. However, paracetamol is also known as acetaminophen internationally. Some brand names for this combination include Tramazac-Co and Tramoltra. Individually, each drug might be marketed under various brand names depending on the manufacturer and region.

How It Works

Pharmacodynamics: The combination exerts its analgesic effect through the synergistic action of its three components. Lornoxicam addresses the inflammatory component of pain, while paracetamol and tramadol act centrally to reduce pain perception. Tramadol’s weak opioid activity provides additional pain relief for more severe cases.

Pharmacokinetics:

• Absorption: All three drugs are well-absorbed orally.
• Metabolism: Lornoxicam is primarily metabolized in the liver by CYP2C9. Paracetamol is primarily metabolized in the liver, with a small fraction undergoing CYP2E1-mediated metabolism to a hepatotoxic metabolite. Tramadol is metabolized in the liver, primarily by CYP2D6, to its active metabolite, O-desmethyltramadol (M1).
• Elimination: Lornoxicam and its metabolites are primarily excreted in urine and feces. Paracetamol is primarily excreted in the urine as glucuronide and sulfate conjugates. Tramadol and its metabolites are primarily excreted in the urine.

Mode of Action: As described above, the combination works at the cellular and molecular level by inhibiting COX enzymes (lornoxicam and paracetamol), modulating opioid receptors (tramadol), and influencing neurotransmitter reuptake (tramadol).

Dosage

Standard Dosage:

Adults: A common formulation contains lornoxicam 8 mg, paracetamol 325 mg, and tramadol 37.5 mg. The initial dose is typically one to two tablets every six to eight hours as needed, not exceeding eight tablets per day. Alternatively, a higher strength tablet with tramadol 75mg and paracetamol 650mg is available, with a maximum dose of four tablets daily. The specific dosage and intervals should be determined based on the intensity of pain.

Children: This combination is generally not recommended for children under 12 years old.

Special Cases:

• Elderly Patients (Over 75): Due to potential age-related decline in renal and hepatic function, start with a lower dose or increase the dosage interval, and closely monitor.
• Patients with Renal Impairment: Moderate impairment (Creatinine clearance 10-30ml/min) may require an increased dosing interval. Severe impairment may necessitate avoiding this combination.
• Patients with Hepatic Dysfunction: Use with caution. Dose adjustments may be necessary based on the severity of impairment. Avoid in severe hepatic impairment.
• Patients with Comorbid Conditions: Careful consideration should be given to patients with conditions such as asthma, bleeding disorders, peptic ulcers, seizures, and respiratory depression.

Clinical Use Cases

Dosage recommendations for specific medical settings would be determined on a case-by-case basis, considering the patient’s overall condition, the severity of pain, and other factors. As this is a combination containing an opioid (Tramadol), its usage in procedures like intubation, surgical recovery or intensive care needs careful consideration.

Dosage Adjustments

Dose modifications are necessary based on individual patient factors including renal/hepatic function, age, and concomitant medications.

Side Effects

Common Side Effects: Nausea, vomiting, dizziness, constipation, drowsiness, headache, dry mouth.

Rare but Serious Side Effects: Allergic reactions (rash, itching, swelling), seizures, respiratory depression, serotonin syndrome (with concomitant serotonergic drugs), hepatotoxicity (especially with paracetamol overdose).

Long-Term Effects: Tolerance, dependence, opioid use disorder (with chronic tramadol use).

Adverse Drug Reactions (ADR): Severe allergic reactions (anaphylaxis), Stevens-Johnson syndrome, liver failure, adrenal insufficiency.

Contraindications

• Hypersensitivity to any component of the combination.
• Acute alcohol intoxication.
• Concurrent use of MAO inhibitors.
• Severe hepatic impairment.
• Uncontrolled epilepsy.
• Severe respiratory depression.

Drug Interactions

• Other opioid analgesics, sedatives (benzodiazepines), antidepressants (SSRIs, tricyclics), alcohol: Increased risk of CNS depression, respiratory depression, serotonin syndrome.
• Anticoagulants, antiplatelets: Increased risk of bleeding.
• CYP2D6 inhibitors/inducers: May alter tramadol metabolism.
• CYP2C9 inhibitors/inducers: May alter lornoxicam metabolism.

Pregnancy and Breastfeeding

Use of this combination should be avoided during pregnancy, especially the third trimester, and breastfeeding, unless the potential benefits outweigh the risks. Tramadol can cause neonatal withdrawal syndrome if used near term.

Drug Profile Summary

• Mechanism of Action: Combined analgesic action via COX inhibition (lornoxicam, paracetamol), opioid receptor modulation, and monoamine reuptake inhibition (tramadol).
• Side Effects: Nausea, vomiting, dizziness, constipation, drowsiness, respiratory depression, seizures, serotonin syndrome.
• Contraindications: Hypersensitivity, acute alcohol intoxication, concurrent MAOI use, severe hepatic/respiratory impairment, uncontrolled epilepsy.
• Drug Interactions: Opioids, sedatives, antidepressants, anticoagulants, CYP2D6/2C9 inhibitors/inducers.
• Pregnancy & Breastfeeding: Avoid.
• Dosage: Varies depending on the formulation. Adult doses are typically administered every 6-8 hours.
• Monitoring Parameters: Pain scores, respiratory rate, blood pressure, liver function tests (especially with prolonged use), signs of opioid withdrawal (with chronic tramadol use).

Popular Combinations

While this combination itself combines three different analgesic mechanisms, it is not commonly combined with additional drugs due to increased risk of adverse effects.

Precautions

As stated earlier, caution is advised in elderly patients, patients with renal or hepatic dysfunction, and those with comorbid conditions. Monitor for side effects, including respiratory depression and serotonin syndrome. Assess for signs of opioid withdrawal with chronic tramadol use. Avoid alcohol and other CNS depressants. Caution patients about operating machinery or driving while taking this medication.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Lornoxicam + Paracetamol + Tramadol?

A: Dosing varies by formulation. A common regimen involves one to two tablets (lornoxicam 8mg/paracetamol 325mg/tramadol 37.5mg) every 6-8 hours as needed, not exceeding 8 tablets/day. Alternatively, a higher strength formulation (tramadol 75mg/paracetamol 650mg) is available, with a maximum of 4 tablets/day.

Q2: Can this combination be used for chronic pain?

A: No, this combination is intended for short-term management of acute pain. Long-term use of tramadol can lead to tolerance, dependence, and opioid use disorder.

Q3: What are the key contraindications for this medication?

A: Contraindications include hypersensitivity to any component, acute alcohol intoxication, concomitant MAOI use, severe hepatic or respiratory impairment, and uncontrolled epilepsy.

Q4: Are there any specific drug interactions I should be aware of?

A: Yes, this combination can interact with other opioids, sedatives, antidepressants, anticoagulants, and medications that affect CYP2D6 and CYP2C9 enzymes. Alcohol should also be avoided.

Q5: Can this medication be used during pregnancy or breastfeeding?

A: It should generally be avoided during pregnancy, especially the third trimester, and breastfeeding due to potential risks to the fetus or neonate.

Q6: What are the common side effects patients might experience?

A: Common side effects include nausea, vomiting, dizziness, constipation, drowsiness, headache, and dry mouth.

Q7: What are the signs of tramadol overdose?

A: Signs of tramadol overdose include pinpoint pupils, respiratory depression, loss of consciousness, and seizures.

Q8: What monitoring parameters are important for patients on this medication?

A: Monitor pain scores, respiratory rate, blood pressure, and liver function (especially with prolonged use). Assess for signs of opioid withdrawal with chronic tramadol use.

Q9: How should I manage a patient experiencing respiratory depression due to tramadol?

A: Administer naloxone as needed, provide respiratory support, and contact emergency medical services immediately.

Q10: Can I prescribe this to a patient with a history of seizures?

A: Tramadol can lower the seizure threshold. Use with extreme caution or avoid in patients with a history of seizures.