Xcel Max

Approved Indications:

• Moderate to moderately severe acute pain in adults where treatment with a combination analgesic is appropriate.
• Postoperative pain management (e.g., dental, musculoskeletal, minor surgery).
• Chronic pain where opioid use is warranted but a full opioid is not indicated.
• Pain in osteoarthritis or musculoskeletal conditions when monotherapy is insufficient.

Off-Label/Clinically Accepted Uses:

• Neuropathic pain (in select patients as adjunct therapy).
• Cancer-related pain in palliative settings (used as part of multimodal analgesia).

Adults (≥18 years):

• Typical dose: 1–2 tablets (each tablet contains 37.5 mg Tramadol HCl + 325 mg Paracetamol) every 4–6 hours as needed.
• Maximum dose: 8 tablets per day (equivalent to 300 mg Tramadol and 2600 mg Paracetamol).
• Duration: For short-term use only, generally ≤5 days.

Elderly (≥65 years):

• Start at the lower end of dosing range.
• Monitor closely for sedation and respiratory depression.
• Avoid or use cautiously in severe hepatic/renal dysfunction.

Pediatric use:

• Not recommended in individuals under 18 years due to the opioid component (Tramadol) and risk of respiratory depression.

Renal Impairment:

• Moderate (CrCl 30–59 mL/min): Extend dosing interval to 6–8 hours.
• Severe (CrCl <30 mL/min): Not recommended.

Hepatic Impairment:

• Mild to moderate: Use with caution.
• Severe: Contraindicated due to increased risk of Paracetamol hepatotoxicity.

Route of Administration: Oral, with or without food. Tablets must be swallowed whole, not crushed or chewed.

Paracetamol + Tramadol Hydrochloride combines two distinct analgesic mechanisms. Tramadol is a synthetic opioid that binds to μ-opioid receptors and also inhibits reuptake of serotonin and norepinephrine, enhancing descending inhibitory pain pathways in the CNS. Paracetamol (acetaminophen) is a non-opioid analgesic and antipyretic that acts mainly in the central nervous system by inhibiting prostaglandin synthesis via COX-3 modulation. Together, they produce synergistic analgesia while minimizing the opioid dose and reducing side effect burden.

Tramadol:

• Absorption: Rapid and nearly complete; peak plasma levels ~2 hours post-dose.
• Bioavailability: ~75%
• Metabolism: Hepatic via CYP2D6 and CYP3A4 to active metabolite O-desmethyltramadol.
• Half-life: Parent ~6 hours; active metabolite ~7.5 hours.
• Excretion: Mainly renal (~90%).

Paracetamol:

• Absorption: Rapid; peak plasma levels in 30–60 minutes.
• Bioavailability: ~63–89%
• Metabolism: Hepatic via glucuronidation and sulfation pathways.
• Half-life: 2–3 hours.
• Excretion: Primarily renal, as conjugated metabolites.

• Pregnancy:
• Tramadol: FDA Pregnancy Category C. Avoid use, especially in the third trimester, due to risk of neonatal opioid withdrawal and respiratory depression.
• Paracetamol: Generally considered safe during pregnancy at therapeutic doses.
• Lactation:
• Tramadol: Excreted in breast milk in low concentrations; avoid due to potential sedation or respiratory depression in the infant.
• Paracetamol: Excreted in minimal amounts; generally considered safe.
• Recommendation: Avoid use of this combination while breastfeeding.

• Analgesic Combination
• Tramadol: Centrally acting synthetic opioid analgesic.
• Paracetamol: Non-opioid analgesic and antipyretic.

• Hypersensitivity to Tramadol, Paracetamol, or any formulation excipients.
• Severe hepatic impairment or active liver disease.
• Severe renal impairment (CrCl <30 mL/min).
• Acute intoxication with alcohol, hypnotics, opioids, or psychotropic drugs.
• Concomitant use with MAO inhibitors or within 14 days of stopping them.
• Patients with uncontrolled epilepsy.
• Pediatric patients under 12 years; post-tonsillectomy/adenoidectomy in under 18 years.

• Addiction and abuse potential: Tramadol is an opioid with potential for misuse, especially with prolonged use.
• Respiratory depression: Risk increased in elderly, debilitated patients, and those with respiratory conditions.
• Hepatotoxicity: Especially at high or prolonged paracetamol doses; avoid alcohol use.
• Serotonin Syndrome: Possible when used with serotonergic drugs (e.g., SSRIs, MAOIs).
• Seizure risk: Tramadol lowers seizure threshold; avoid in epilepsy or head trauma.
• Renal/Hepatic impairment: Use only if benefits outweigh risks, with strict monitoring.

Common:

• CNS: Dizziness, headache, drowsiness, fatigue.
• GI: Nausea, vomiting, constipation, dry mouth.
• General: Sweating, flushing.

Less Common:

• Anxiety, insomnia, tremor, blurred vision.

Serious/Rare:

• Seizures, respiratory depression, serotonin syndrome, anaphylaxis, liver failure (paracetamol overdose), Stevens-Johnson Syndrome, toxic epidermal necrolysis.

• MAO inhibitors: Contraindicated—may cause severe serotonin toxicity.
• SSRIs, SNRIs, tricyclic antidepressants: Increased risk of serotonin syndrome.
• CYP2D6 and CYP3A4 inhibitors (e.g., fluoxetine, erythromycin): May elevate tramadol levels, increasing toxicity.
• CYP inducers (e.g., carbamazepine): May reduce tramadol efficacy.
• Warfarin: Prolonged paracetamol use may potentiate INR.
• Alcohol: Increases risk of hepatotoxicity and CNS depression.

• FDA & EMA warning (2022–2023): Strengthened labeling regarding risk of respiratory depression in pediatric use and serotonin syndrome with serotonergic drugs.
• Dosage limits revised: To ensure maximum daily dose of paracetamol does not exceed 3000–4000 mg.
• WHO guidance: Recommends combination use only for acute moderate pain and with strict limits on duration and monitoring.

• Temperature: Store below 25°C (77°F).
• Humidity: Keep in a dry environment; avoid exposure to moisture.
• Light Protection: Store in original packaging.
• Handling: Do not crush or chew tablets. Keep out of reach of children.
• Reconstitution/Refrigeration: Not applicable.