At a glance......
- 1 Mechanism of Action of Tapentadol
- 2 Indications of Tapentadol
- 3 Therapeutic Uses of Tapentadol
- 4 Contra-Indications of Tapentadol
- 5 Dosage of Tapentadol
- 6 Side effects of Tapentadol
- 7 Drug Interactions of Tapentadol
- 8 Pregnancy & Lactation of Tapentadol
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Tapentadol is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration and lasts for 4–6 hours.
It is similar to tramadol in its dual mechanism of action; namely, its ability to activate the mu opioid receptor and inhibit the reuptake of norepinephrine. Unlike tramadol, it has only weak effects on the reuptake of serotonin and is a significantly more potent opioid with no known active metabolites. Tapentadol is not a pro-drug and therefore does not rely on metabolism to produce its therapeutic effects; this makes it a useful moderate-potency analgesic option for patients who do not respond adequately to more commonly used opioids due to genetic disposition poor metabolizers of , as well as providing a more consistent dosage-response range among the patient population.
Mechanism of Action of Tapentadol
Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central mu-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurons of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in a dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbinereversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and a2-adrenoceptors seen at spinal levels but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain.
Tapentadol acts on the opioid receptors through its major active metabolite desmetapentadol, which has as much as 700-fold higher affinity for the MOR relative to tapentadol. Moreover, tapentadol itself has been found to possess no efficacy in activating the MOR in functional activity assays, whereas desme tapentadol activates the receptor with high intrinsic activity ( equal to that of morphine). As such, desme tapentadol is exclusively responsible for the opioid effects of tapentadol. Both tapentadol and desme tapentadol have pronounced selectivity for the MOR over the DOR and KOR in terms of binding affinity. Tramadol has been found to possess the following actions
- Agonist of the μ-opioid receptor (MOR) and to a far lesser extent of the δ-opioid receptor (DOR) and κ-opioid receptor (KOR)
- Serotonin reuptake inhibitor (SRI) and norepinephrine reuptake inhibitor (NRI); hence, an SNRI
- Serotonin 5-HT2C receptor antagonist
- M1 and M3 muscarinic acetylcholine receptor antagonist
- α7 nicotinic acetylcholine receptor antagonist
- NMDA receptor antagonist (very weak)
- TRPA1 inhibitor
Indications of Tapentadol
- Cervical spondylosis
- Radiating pain due to nerve compression
- Demyelinating nerve pain
- Low back pain
- Chest pain
- Ankylosing spondylitis
- Acute pain due to trauma
- Accidental pain due to road traffic accident
- Acute abdominal pain due to gastritis/appendicitis
- Pain due to specially musculoskeletal system
- Muscles stiffness in nerve diseases
- Morning stiffness
- Multiple joint pain
- Muscles stiffness in spinal cord
- Pain caused by nonarticular rheumatism
- Periarthritis ofscapulohumerals
- The immediate-release formulation of tapentadol is indicated for the relief of moderate to severe acute pain. The long-acting formulation serves as a continuous, around-the-clock analgesic that is indicated for the relief of moderate to severe chronic pain or neuropathic pain associated with diabetic peripheral neuropathy.
Therapeutic Uses of Tapentadol
- Nucynta (tapentadol) is indicated for the relief of moderate to severe acute pain in patients 18 years of age or older.
- Tapentadol is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate; neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Usage
- Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve Nucynta ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Nucynta ER is not indicated as an as-needed (prn) analgesic.
- Tapentadol is a combined mu-opioid receptor agonist and noradrenaline reuptake inhibitor
- This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care.
- The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use.
- CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee.
- It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death.
Contra-Indications of Tapentadol
Tapentadol is contraindicated in those with hypersensitivity,
- Allergy to tapentadol or any other ingredients in the medicine;
- Allergy to medicines called opioid antagonists (e.g. codeine, morphine);
- Consumed alcoholor taken another drug which affects your brain. These include:
- Some painkillers, including opioid pain killers;
- Hypnotic drugs;
- Psychotropic drugs;
- Used monoamine oxidase inhibitors (MAOIs) such as phenelzine or tranylcypromine in the past 14 days;
- History of peptic ulcer disease,
- Gastrointestinal bleeding,
- Alcohol intolerance,
- Renal impairment,
- Angioedema, and asthma
- Acute intoxication with alcohol,
- Psychotropic medicinal products,
- Heart failure,
- Coagulation disorders,
- Renal impairment,
- Hepatic impairment.
Dosage of Tapentadol
Strenghts: 50 mg, 75 mg, or 100 mg
- 50 mg, 75 mg, or 100 mg orally every 4 to 6 hours depending upon pain intensity, with or without food.
- On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability. Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are, therefore, not recommended.
- Initial: 50 mg twice daily (recommended interval: 12 hours); titrate in increments of 50 mg no more frequently than twice daily every 3 days to the effective dose (therapeutic range: 100 to 250 mg twice daily) (maximum dose: 500 mg/day)
- Initial: 50 mg titrated to an effective dose; titrate in increments of 50 mg no more frequently than twice daily every 3 days (therapeutic range: 100 to 250 mg twice daily) (maximum dose: 500 mg/day). Note: No adequate data on converting patients from other opioids to tapentadol extended release.
- Conversion from immediate release to extended release: Convert using same total daily dose but divide into two equal doses and administer twice daily (recommended interval: 12 hours) (maximum dose: 500 mg/day).
Side effects of Tapentadol
The most common
- Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting or abdominal pain.
- Drowsiness and lightheadedness
- Nausea and vomiting
- joint pain
- Nausea and vomiting
- Severe stomach ache
- Severe diarrhea
- Vaginal thrush
- Skin rash
- Chest pain
- Diarrhea or loose stools
- Difficulty with breathing
- Muscle pain
- Abdominal or stomach pain,
- Chills or fever
- Joint or back pain
- Muscle aching or cramping
- Muscle pains or stiffness
- Chest pressure or squeezing pain in the chest
- Excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- Loss of muscle coordination
- Sleepiness or unusual drowsiness
- Clumsiness or unsteadiness
- change in vision
- abnormal or fast heart rate
- weight loss
- chest pain or tightness
- a cough
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- extra heartbeats
- a headache
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
Drug Interactions of Tapentadol
Tapentadol may interact with following drugs, supplements & may change the efficacy of drugs
- anti-emetic medications (serotonin antagonists; e.g., granisetron, ondansetron)
- antihistamines (e.g,. cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- aminoglycoside antibiotics (e.g., amikacin, gentamicin, tobramycin)
- angiotensin-converting enzyme inhibitors (ACEIs; e.g., captopril, enalapril, ramipril)
- angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
- beta-adrenergic blockers (e.g., metoprolol, atenolol)
- barbiturates (e.g., butalbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, )
- 5-ASA medications (e.g. sulfasalazine)
- other non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, ketorolac, naproxen)
- Omega-3 fatty acids
- quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine,fluoxetine, paroxetine, sertraline)
- serotonin/norepinephrine reuptake inhibitors (SNRIs; e.gduloxetine, )
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
Pregnancy & Lactation of Tapentadol
FDA Pregnancy Category C
This medication should not be used during pregnancy, prior to or during labour. If you become pregnant while taking this medication, contact your doctor immediately.
It is not known if tapentadol passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.