Tapenta

• Approved Indications:
• Management of moderate to severe acute pain in adults when opioid analgesia is appropriate.
• Management of moderate to severe chronic pain, including neuropathic pain associated with diabetic peripheral neuropathy (DPN).
• Treatment of severe chronic pain requiring continuous, long-term opioid treatment where alternative therapies are inadequate.
• Off-label Uses:
• Postoperative pain management.
• Cancer-related pain.
• Other neuropathic pain conditions resistant to conventional treatment.

• Adults:
• Immediate-release tablets: Initial dose 50 mg every 4 to 6 hours as needed; maximum daily dose 600 mg.
• Extended-release tablets: Start with 50 mg twice daily; titrate based on pain control and tolerance; maximum 500 mg daily.
• Elderly:
• Begin at the lowest dose; monitor closely due to increased sensitivity.
• Pediatrics:
• Safety and efficacy not established; not recommended.
• Renal Impairment:
• Use caution in moderate to severe impairment; dose reduction may be necessary; avoid in end-stage renal disease.
• Hepatic Impairment:
• Avoid in severe impairment; use lower doses cautiously in mild/moderate cases.
• Route: Oral administration only.
• Instructions: Swallow tablets whole with water; do not crush or chew extended-release tablets.
• Duration: Tailor duration individually; reassess regularly.

Tapentadol hydrochloride provides analgesia through dual mechanisms: it acts as a mu-opioid receptor agonist, inhibiting ascending pain signals in the central nervous system, and simultaneously inhibits norepinephrine reuptake, enhancing descending inhibitory pathways in the spinal cord. This combination results in effective pain relief with a potentially lower incidence of opioid-related side effects compared to traditional opioids.

• Absorption: Rapid oral absorption with peak plasma levels in 1.25 hours (immediate-release) and 3-6 hours (extended-release). Bioavailability approximately 32%.
• Distribution: Volume of distribution ~342 liters; low plasma protein binding (~20%).
• Metabolism: Mainly metabolized via phase 2 glucuronidation (UGT1A9 and UGT2B7); minor involvement of CYP enzymes (CYP2C9, CYP2C19, CYP2D6).
• Elimination: Half-life approximately 4 hours (immediate-release) and 5-6 hours (extended-release). Excreted mostly as metabolites via urine (>99%), with less than 1% unchanged drug.

• Pregnancy: FDA Category C. Animal studies indicate possible risks; no adequate human data. Use only if benefits justify risks.
• Lactation: Tapentadol is excreted in breast milk. Breastfeeding is not recommended during treatment due to potential opioid effects on the infant.
• Note: Limited human data; exercise caution.

• Opioid analgesic
• Dual mechanism analgesic (mu-opioid receptor agonist and norepinephrine reuptake inhibitor)

• Hypersensitivity to tapentadol or formulation components
• Severe respiratory depression
• Acute or severe bronchial asthma without respiratory support
• Paralytic ileus or gastrointestinal obstruction
• Concomitant or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs)

• Risk of life-threatening respiratory depression, especially in opioid-naïve or respiratory compromised patients.
• Potential for abuse, addiction, and misuse leading to overdose and death.
• Avoid abrupt discontinuation; taper dose gradually to prevent withdrawal.
• Use with caution in patients with increased intracranial pressure or head trauma.
• Orthostatic hypotension risk; monitor blood pressure.
• Risk of serotonin syndrome with serotonergic drugs.
• Monitor for adrenal insufficiency and androgen deficiency during prolonged therapy.
• Increased seizure risk in predisposed patients.
• Concurrent CNS depressants and alcohol may enhance sedation and respiratory depression.

·         Common: Dizziness, somnolence, headache, nausea, vomiting, constipation, dry mouth, fatigue.

·         Serious/Rare: Respiratory depression, seizures, serotonin syndrome, anaphylaxis, hepatic dysfunction, pancreatitis.

·         Side effects generally dose-related and often occur early in treatment.

• CYP450 enzymes: Minor involvement; strong CYP3A4 or CYP2C9 inhibitors/inducers may alter levels slightly.
• CNS depressants (e.g., benzodiazepines, alcohol) increase sedation and respiratory depression risk.
• Serotonergic drugs (SSRIs, SNRIs, triptans) increase serotonin syndrome risk.
• Drugs affecting norepinephrine reuptake may enhance effects.
• Avoid alcohol to reduce enhanced CNS depression.

• Emphasis on opioid stewardship, patient risk assessment, and monitoring.
• Highlighted serotonin syndrome risk with serotonergic agents.
• Updated labeling on abuse potential and necessity for risk mitigation.
• Multimodal pain management strategies include tapentadol for mixed pain types.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Do not freeze.
• Keep container tightly closed and out of reach of children.