Tapentadol (Palexia) is a centrally acting orally available opioid medicine that is used to treat moderate to severe pain that does not respond to non-opioid analgesics.

Indications of Tapentadol (Palexia):

• Neuropathic pain associated with diabetic peripheral neuropathy:

  • Extended-release: It is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy severe enough to require daily, around-the-clock, long-term opioid treatment, and for which alternative treatment options are inadequate.

Note: Due to a high risk for addiction and safety concerns compared to modest pain reduction, tapentadol ER is not usually recommended as first- or second-line therapy.

• Pain management:

  • Immediate release:

    • It is useful in the management of acute pain severe enough to require an opioid analgesic and not responding to alternative treatments in adults.

  • Extended-release:

    • It is required for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment, and is unresponsive to alternative therapy.

  • Limitations of use:

    • In patients where alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain, tapentadol is indicated. Tapentadol ER is not indicated as an as-needed analgesic.

Tapentadol (Palexia) dose in adults:

Note:

• Doses vary according to pain severity with respect to the patient’s previous experience with similar opioid analgesics.
• Immediate-release opioid or nonopioid drugs can be given for rescue relief of breakthrough pain and during dosage adjustments in patients using extended-release tapentadol.

Opioid tolerance is defined as:

• Patients already taking at least morphine 60 mg orally daily, oxymorphone 25 mg orally daily, transdermal fentanyl 25 mcg per hour, oxycodone 30 mg orally daily, hydromorphone 8 mg orally daily, hydrocodone 60 mg orally daily or an equivalent dose of another opioid for at least 1 week.

Tapentadol (Palexia) dose in the treatment of neuropathic pain associated with diabetic peripheral neuropathy:

• Extended-release:

  • Opioid naive (the first opioid analgesic/patients who are opioid intolerant):

    • Initial: 50 mg per oral every 12 hours.

  • Conversion from other opioids to tapentadol ER:

    • Initial: 50 mg per oral every 12 hours

  • Conversion from tapentadol immediate release to ER:

    • Convert using the same total daily dose but divide into 2 equal doses and administer every 12 hours.

  • Conversion from methadone to tapentadol ER:

  • Methadone has a long half-life and can accumulate in the plasma.
  • Converting methadone to another opioid needs close monitoring.
  • The ratio between methadone and other opioid agonists varies widely according to previous dose exposure.

  • Dosage titration:

    • Titrate in increments of 50 mg no more frequently than b.i.d daily every 3 days to an effective dose.
    • therapeutic range: 100 to 250 mg every 12 hours.

Tapentadol (Palexia) Dose in Pain management:

• Immediate-release tablets and solution:

  • Day 1:

    • 50 to 100 mg (2.5 to 5 mL) per oral every 4 to 6 hours as needed;
    • may administer a second dose ≥1 hour after the initial dose (maximum dose on the first day: 700 mg/day).

  • Day 2 and subsequent dosing:

    • 50 to 100 mg (2.5 to 5 mL) every 4 to 6 hours as needed (maximum: 600 mg/day).

  • Conversion from tapentadol immediate release to ER:

    • Convert using the same total daily dose but divide into 2 equal doses and given every 12 hours.

  • Extended-release:

    • Opioid naive (as the first opioid analgesic/patients who are opioid intolerant):

      • Initial: 50 mg per oral every 12 hours.

    • Conversion from other opioids to tapentadol ER:

      • Initial: 50 mg per oral every 12 hours.

    • Conversion from tapentadol immediate release to ER:

      • Convert using the same total daily dose but divide into 2 equal doses and administer every 12 hours.

    • Conversion from methadone to extended-release tapentadol:

      • Methadone has a long half-life and can accumulate in the plasma.
      • Converting methadone to another opioid required close monitoring.
      • The ratio between methadone and other opioid agonists varies widely according to previous dose exposure.

    • Dosage titration:

      • Titrate in increments of 50 mg no more frequently than b.i.d daily every 3 days to an effective dose.
      • therapeutic range: 100 to 250 mg every 12 hours.

    • Discontinuation of therapy:

      • The drug should be slowly tapered when discontinuing chronic opioid therapy.
      • An optimal universal tapering schedule for all patients has not been established.
      • Proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days).
      • In order to reduce withdrawal effects, tapering schedules should be individualized taking into account patient-specific goals and concerns as well as the pharmacokinetics of the opioid being tapered.
      • In the case of long term opioids, slower tapering may be appropriate in patients especially in the final stage of tapering, whereas patients with severe adverse events need more rapid tapering.
      • Signs/symptoms of withdrawal should be carefully observed.
      • In the case of withdrawal symptoms, the slow taper should be done. Alterations may include increasing the interval between dose reductions, decreasing the amount of daily dose reduction, holding the taper and restarting when the patient is ready, and/or combination of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms.
      • Non-opioid analgesics as needed for pain management can be given during the taper, while withdrawal symptoms are managed with nonopioid adjunctive treatments.

Tapentadol (Palexia) use in Children:

• Data in this regard is limited.
• One study evaluated Tapentadol oral solution as a single dose of 1 mg/kg in children aged 6 to <18 years.
• The drug was well-tolerated and produced similar serum concentrations as the administration of 50–100 mg tapentadol immediate-release tablets in adults [Ref].

Pregnancy Risk Category: C

[US Boxed Warning]

• Studies on animal reproduction revealed negative outcomes.
• Opioids can cross the placenta.
• Tapentadol can cause fatal neonatal withdrawal syndrome in newborns if it is continued in pregnancy.
• These symptoms can include fever, temperature instability, gastrointestinal problems with diarrhea, vomiting and poor feeding/weight gain), as well as neurologic features such high-pitched crying, hyperactivity or increased muscle tone, abnormal sleep patterns, excessive wakefulness, increased wakefulness, increased irritability, seizure/tremor, yawning, and seizure.
• Opioid-dependent mothers may give birth to infants who are also dependent.
• Pregnancy patients should be aware of the dangers associated with prolonged opioid therapy.
• Maternal use can lead to birth defects, preterm deliveries, and poor fetal growth.
• Monitor newborns for signs of respiratory depression or psycho-physiologic effects from opioid therapy during labor.
• Alternate agents are recommended for pains that include labor, immediate postpartum, and chronic noncancer pains in pregnant women, or during pregnancy.

Tapentadol use during breastfeeding:

• Tapentadol may be excreted in breastmilk, but only limited data is available.
• Breastfeeding women should not use opioid analgesics for pain after giving birth.
• Breastfeeding mothers should use the lowest effective dose for the shortest time in order to minimize adverse reactions in their infants.
• A single, occasional dose of opioid analgesics might be suitable for breastfeeding.
• If a mother is breastfeeding, she should monitor her infants for signs such as drowsiness or sedation.
• The newborn can experience withdrawal syndrome if they stop breastfeeding or discontinue maternal therapy.
• The manufacturer suggests that the mother decide whether to discontinue breastfeeding or if the drug should be used. This decision will depend on the importance to the mother of the drug's side effects.

Tapentadol (Palexia) Dose adjustment in renal disease:

• Creatinine clearance ≥30 mL/minute:

  • No dosage adjustment is necessary.

• Creatinine clearance <30 mL/minute:

  • It should not be used.

Tapentadol (Palexia) dose adjustment in liver disease:

• Mild impairment (Child-Pugh class A):

  • No dosage adjustment is necessary.

• Moderate impairment (Child-Pugh class B):

  • Immediate-release:

    • Initial: 50 mg every 8 hours or longer.
    • maximum: 150 mg/24 hours.
    • Further treatment for the maintenance of analgesia may be achieved by either shortening or lengthening the dosing interval.

  • Extended-release:

    • Initial: 50 mg every 24 hours or longer.
    • maximum: 100 mg/day.

• Severe impairment (Child-Pugh class C):

  • Use not recommended.

Immediate-release Tapentadol (Palexia):

Common Side effects:

• Central nervous system:

  • Dizziness
  • Drowsiness

• Gastrointestinal:

  • Nausea
  • Vomiting

Rare Side Effects of Tapentadol (Palexia):

• Central Nervous System:

  • Fatigue
  • Insomnia
  • Abnormal Dreams
  • Anxiety
  • Confusion
  • Lethargy

• Dermatologic:

  • Pruritus
  • Hyperhidrosis
  • Skin Rash

• Endocrine & Metabolic:

  • Hot Flash

• Gastrointestinal:

  • Constipation
  • Xerostomia
  • Decreased Appetite
  • Dyspepsia

• Genitourinary:

  • Urinary Tract Infection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Tremor

• Respiratory:

  • Nasopharyngitis
  • Upper Respiratory Tract Infection

Extended-Release Tapentadol (Palexia):

Common Side Effects:

• Central Nervous System:

  • Dizziness
  • Headache
  • Drowsiness

• Gastrointestinal:

  • Nausea
  • Constipation
  • Vomiting

Rare Side Effects of Tapentadol (Palexia):

• Cardiovascular:

  • Hypotension

• Central Nervous System:

  • Fatigue
  • Anxiety
  • Insomnia
  • Irritability
  • Lethargy
  • Abnormal Dreams
  • Vertigo
  • Chills
  • Depression
  • Hypoesthesia
  • Lack Of Concentration
  • Nervousness
  • Sedation
  • Withdrawal Syndrome

• Dermatologic:

  • Pruritus
  • Hyperhidrosis
  • Skin Rash

• Endocrine & Metabolic:

  • Hot Flash

• Gastrointestinal:

  • Diarrhea
  • Xerostomia
  • Decreased Appetite
  • Dyspepsia
  • Abdominal Distress

• Genitourinary:

  • Erectile Dysfunction

• Neuromuscular & Skeletal:

  • Tremor
  • Weakness

• Ophthalmic:

  • Blurred Vision

• Respiratory:

  • Dyspnea

Contraindications to Tapentadol (Palexia):

• Hypersensitivity to tapentadol and any other component of the formulation (eg anaphylaxis or angioedema).
• GI obstruction, including paralytic ileus
• Hypercapnia or severe asthma in an environment that does not provide adequate facilities for resuscitation
• Grave respiratory depression
• Use within 2 weeks of MAO inhibitors
• Pregnancy, breastfeeding, use during labor or delivery
• COPD, cor Pulmonale, Acute Respiratory Depression
• Acute appendicitis and pancreatitis
• Severe hepatic impairment (Child Puugh class C).
• Severe renal impairment (CrCl >30 mL/minute).
• Irregular GI, including strictures or ileus
• Acute alcoholism, delirium tremens
• Severe CNS depression, seizure disorders
• An increase in intracranial pressure, or a head injury
• You can manage mild, intermittent or short-term pain with an alternative medication
• Extended-release tablets for the management of perioperative pain

Warnings and precautions

• CNS depression:

  • Tapentadol may cause CNS depression that can lead to impairment of physical and mental abilities. It is important to warn patients not to drive or operate machinery.

• Hypotension

  • It can lead to orthostatic hypotension or syncope. Therefore, monitoring is necessary after dose adjustment.
  • Hypovolemia, acute MI and drugs that can exaggerate hypotensive effects (e.g. phenothiazines, general anesthetics) increase the risk.
  • Patients with circulatory shock should not use this product.

• Respiratory depression [US Boxed Warning]

  • Opioids can cause serious respiratory depression. Therefore, it is important to monitor your dose during initiation and escalation.
  • Extended-release tablets may be broken down, chewed, or dissolved by crushing. This can lead to rapid release and possibly fatal side effects.
  • Carbon dioxide retention due to opioid-induced respiratory depression can increase the sedating effects.

• Serotonin syndrome:

  • Tapentadol combined therapy with serotonergic agents (eg SSRIs and SNRIs), or agents that impair serotonin metabolism (eg MAO inhibitors to treat psychiatric conditions, other MAO inhibitors [ie linezolid, intravenous methyleneblue]) can result in fatal serotonin syndrome.
  • It comes with:
    • agitation, hallucinations and delirium.
    • neuromuscular changes (eg, tremor, rigidity, myoclonus);
    • GI symptoms (eg, nausea, vomiting, diarrhea);
    • and/or seizures.
  • These symptoms should always be monitored.
  • If you notice any symptoms or signs, it is important to stop immediately.

• Conditions abdominales:

  • Patients with acute abdominal conditions may not be diagnosed or treated appropriately.

• Adrenocortical Insufficiency

  • Long-term therapy can be used to treat secondary hypogonadism, which can lead to infertility, sexual dysfunction, and mood disorders.
  • Patients with adrenal insufficiency (including Addison disease) should not use it.

• Insufficiency of the biliary tract:

  • It can cause spasms of the sphincter Oddi. Patients with acute pancreatitis or biliary dysfunction should be cautious when using it.

• CNS depression/coma:

  • CO retention can cause impaired consciousness and intracranial effects.

• Delirium tremens:

  • Patients with delirium-tremens should be taken with caution

• Head trauma

  • It can increase the ICP. Patients with intracranial lesion or a head injury should exercise extreme caution.

• Hepatic impairment

  • In severe hepatic impairment, it is not recommended.
  • Patients with mild hepatic impairment may require dose adjustment.

• Mental health conditions

  • It is important to use it with caution in patients suffering from depression, anxiety disorders, or post-traumatic stress disorder.

• Obesity:

  • Patients who are severely obese should be taken with caution

• Prostatic hyperplasia/urinary restriction:

  • Patients with prostatic hyperplasia or urinary stricture should be cautious.

• Psychosis:

  • Patients with toxic psychosis should be treated with caution.

• Renal impairment

  • In severe renal impairment, it is not recommended.
  • Patients with mild or moderate renal impairment should be cautious.

• Respiratory disease

  • With COPD, cor Pulmonale, decreased respiration reserve, hypoxia and hypercarbia, the risk of developing respiratory depression is significantly higher. Therefore, strict monitoring is required when starting or even administering therapeutic doses.
  • These patients should prefer nonopioid analgesics.

• Seizures:

  • It can cause seizures to worsen, so patients who have had seizures in the past or are at risk of developing seizures should not use it.

• Sleep-disordered breathing

  • With severe or moderately disturbed sleep, it should not be used.
  • You should use it with extreme caution, as there are risk factors for sleep-disordered or obese breathing.

• Thyroid dysfunction:

  • Patients with thyroid dysfunction should be cautious.

Monitoring parameters:

• BP, pulse
• Respiratory and mental status
• bowel function
• Relief of symptoms
• signs/symptoms of misuse, abuse, or addiction
• signs or symptoms of hypogonadism or hypoadrenalism

Alternate recommendations:

Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder):

• Benefits or risks of opioid therapy should be observed within 1 month of starting treatment and with dose increase, then every 3 monthly during therapy or more frequently in patients at increased risk of overdose or opioid use disorder.
• Urine drug testing is needed before starting treatment and re-checking should be done at least yearly.
• Clinicians should review state prescription drug monitoring program data before starting and periodically during therapy (frequency ranging from every prescription to every 3 months).

How to administer Tapentadol (Palexia)?

• It should be orally given without regard to meals.

ER tablets:

• Tablets should be swallowed as a whole without splitting, crushing, breaking, chewing, cutting, or dissolving.
• One tablet at a time with sufficient water should be taken to ensure complete swallowing immediately after placing it in the mouth.

Oral solution:

• The enclosed calibrated oral syringe should be used to ensure accurate dose measurement and administration.

Mechanism of action of Tapentadol (Palexia):

• Tapentadol inhibits ascending pain pathways through binding to mopiate receptors within the CNS, thereby changing the perception and response to pain.
• It causes an increase in pain pathways modification by blocking the reuptake norepinephrine.

Absorption: Rapid and complete.

Protein binding: 20%

Metabolism:

• Extensive metabolism, including the first-pass metabolism; metabolized primarily via phase 2 glucuronidation to glucuronides (major metabolite: tapentadol-O-glucuronide). minimal phase 1 oxidative metabolism; also metabolized to a lesser degree by CYP2C9, CYP2C19, and CYP2D6; all metabolites pharmacologically inactive.

Bioavailability: 32%

Half-life elimination:

• Immediate release: 4 hours.
• Long-acting formulations: 5-6 hours.

Time to peak plasma concentrations:

• Immediate-release: 1.25 hours.
• Long-acting formulations: 3-6 hours.

Excretion: Urine (99%: 70% conjugated metabolites; 3% unchanged drug)

International Brands of Tapentadol:

• Nucynta
• Nucynta ER
• Cynta
• Dol-Proxyvon
• Laraprex
• Lopenta
• Medtadol
• Nucynta SR
• Nucytadol
• Paincure
• Palexia
• Palexia Depot
• Palexia IR
• Palexia PR
• Palexia Retard
• Palexia SR
• Palexias
• Tapcynta
• Tapenta
• Vorth-TP
• Yantil
• Yantil Retard
• {alexia SR

Tapentadol Brand Names in Pakistan:

Tydel