Pentazocin

Pentazocin is an Opioid Partial agonist-antagonist belonging to the analgesic class.

Pentazocin is an analgesic used to treat moderate to severe pain.

Pentazocin is absorbed well from the gastrointestinal tract. Time taken to reach peak plasma concentration is approximately 1-3 hours. Pentazocin is primarily Metabolized in the liver via oxidative and glucuronide conjugation pathways; undergoes extensive first-pass metabolism. Mainly excreted Via urine (small amounts as unchanged drug).

Pentazocin shows side effects like Feeling very tired, lightheadedness, drowsiness, mood changes, headache, upset stomach, constipation, stomach pain, rash, difficulty urinating.

Pentazocin is available in the form of Oral tablet and Injectable solution.

Pentazocin is available in India, US, China, Japan, Poland, Netherland, Canada, France, Italy, Germany, and Australia.

Pentazocin is an Analgesic belonging to the class Opioid agonist-antagonist.

Pentazocin is agonist of kappa opiate receptors and partial agonist of mu opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces analgesia, respiratory depression, and sedation similar to opioids.

The effect of Pentazocin can be observed within 15 to 30 minutes of an oral, subcutaneous, or intramuscular dose and within 2 to 3 minutes of an intravenous dose.

The effect of Pentazocin lasts for an average duration of 3 hours.

Pentazocin is available in the form of Oral tablet and Injectable solution.

Pentazocin Injectable solution is given via subcutaneous, intramuscular, and intravenous route.

Pentazocin is a potent analgesic drug used in the treatment of moderate to severe pain for which alternative treatments are inadequate. Pentazocin is also used as a pre-anesthetic or preoperative medication and as a supplement to surgical anesthesia. Pentazocin should be used with extreme caution due to the increased risk of addiction.

Pentazocin is an Opioid agonist-antagonist belonging to the analgesic class.

Pentazocin is agonist of kappa opiate receptors and partial agonist of mu opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces analgesia, respiratory depression, and sedation like opioids.

Pentazocin is approved for use in the following clinical indications

• Pentazocin is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
• Pentazocin may also be used for preoperative or preanesthetic medication and as a supplement to surgical anesthesia.

• Anesthesia, pain management

IM, Subcutaneous Dose: 30 mg every 3 to 4 hours; do not exceed 60 mg/dose (maximum: 360 mg/day).

IV Dose: 30 mg every 3 to 4 hours; do not exceed 30 mg/dose (maximum: 360 mg/day).

• Labor pain

IM Dose: 30 mg once.

IV Dose: 20 mg every 2 to 3 hours as needed (maximum total dose: 60 mg).

• Pain management

Oral Dose

Initial: 50 mg every 4 hours; titrate per response and tolerability to 50 to 100 mg every 3 to 4 hours. Maximum dose: 600 mg/day.

Pentazocin is available in various strengths as 30 mg/mL.

Pentazocin is available in the form of Oral tablet and Injectable solution.

Pentazocin is contraindicated in patients with

• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus.
• Hypersensitivity to pentazocine (e.g., anaphylaxis).

• Cardiovascular effects
• May increase systemic and pulmonary arterial pressure and systemic vascular resistance; use with caution in patients who may not tolerate these alterations in hemodynamics (eg, acute myocardial infarction [MI]).
• CNS depression
• May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension
• May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.
• Injection-site reactions

Severe sclerosis of the skin, subcutaneous tissues, and underlying muscle has occurred at the injection-site following multiple injections; avoid SUBQ use unless absolutely necessary; rotate sites of injection.

• Respiratory depression

Fatal respiratory depression may occur. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately in the event of a known or suspected overdose.

• Abdominal conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency

Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis.

• Biliary tract impairment

Use with caution in patients with biliary tract dysfunction or acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

• CNS depression/coma

Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO2 retention.

• Delirium Tremors

Use with caution in patients with delirium Tremors.

• Head trauma

Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment

Use with caution in patients with hepatic impairment.

• Mental health conditions

Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, posttraumatic stress disorder) due to potential increased risk for opioid use disorder and overdose; more frequent monitoring is recommended.

• Obesity

Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture

Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis

Use with caution in patients with toxic psychosis.

• Renal impairment
• Use with caution in patients with renal impairment.
• Respiratory disease

Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Seizures

Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.

• Sleep-related disorders

Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and CNS depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing.

• Thyroid dysfunction

Use with caution in patients with thyroid dysfunction.

• Alcohol

Patients should not consume alcoholic beverages or use prescription or non prescription products containing alcohol while taking pentazocine.

• Benzodiazepines or other CNS depressants

Concomitant use may result in respiratory depression and sedation, which may be fatal. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.

Alcohol should not be consumed while receiving this medicine since it may increase the risk of drowsiness, lightheadedness, impairment in thinking and judgment, etc.

This medicine is not recommended for use in pregnant women unless necessary. All the risks and benefits should be considered before taking this medicine.

This medicine is not recommended for use in breastfeeding women.

• Common

Circulatory depression, facial edema, flushing, hypertension, hypotension, increased peripheral vascular resistance, shock, syncope, tachycardia, Central nervous system depression, chills, confusion, disorientation, dizziness, drowsiness, drug dependence (physical and psychological), euphoria, excitement, hallucination, headache, insomnia, irritability, malaise, nightmares, paresthesia, sedation, Dermatitis, diaphoresis, erythema multiforme, pruritus, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, Abdominal distress, anorexia, constipation, diarrhea, dysgeusia, nausea, vomiting, xerostomia, Urinary retention, Agranulocytosis (rare), decreased white blood cell count, eosinophili, Anaphylaxis, Injection site reaction (tissue damage and irritation), Tremor, weakness, Blurred vision, diplopia, miosis, nystagmus, Tinnitus, Dyspnea, respiratory depression (rare).

• Rare

Allodynia (opioid-induced hyperalgesia), hypogonadism.

• Alizapride

May enhance the CNS depressant effect of CNS Depressants.

• Alvimopan

Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation.

Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation.

• Amphetamines

May enhance the analgesic effect of Opioid Agonists.

• Anticholinergic Agents

May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination.

• Azelastine (Nasal)

May enhance the CNS depressant effect of CNS Depressants.

• Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.

• Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Bromopride

May enhance the CNS depressant effect of CNS Depressants.

• Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

• Buprenorphine

Opioids (Mixed Agonist / Antagonist) may diminish the therapeutic effect of Buprenorphine. This combination may also induce opioid withdrawal.

• Cannabinoid-Containing Products

CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products.

• Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

• Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

• CNS Depressants

May enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

• Daridorexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended.

• Desmopressin

Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

• Dexmedetomidine

CNS Depressants may enhance the CNS depressant effect of Dexmedetomidine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants and consider dose reductions of either agent to avoid excessive CNS depression.

• Difelikefalin

May enhance the CNS depressant effect of CNS Depressants.

• Dimethindene (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Diuretics

Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.

• Droperidol

May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use.

• Eluxadoline

Opioid Agonists may enhance the constipating effect of Eluxadoline.

• Flunarizine

CNS Depressants may enhance the CNS depressant effect of Flunarizine.

• Flunitrazepam

CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available.

• Gastrointestinal Agents (Prokinetic)

Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Hydroxyzine

May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant.

• Ixabepilone

May enhance the CNS depressant effect of CNS Depressants.

• Kava Kava

May enhance the CNS depressant effect of CNS Depressants.

• Kratom

May enhance the CNS depressant effect of CNS Depressants.

• Lemborexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary.

• Lisuride

May enhance the CNS depressant effect of CNS Depressants.

• Lofexidine

May enhance the CNS depressant effect of CNS Depressants.

• Magnesium Sulfate

May enhance the CNS depressant effect of CNS Depressants.

• Methotrimeprazine

CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression.

• Metoclopramide

May enhance the CNS depressant effect of CNS Depressants.

• Metyrosine

CNS Depressants may enhance the sedative effect of Metyrosine.

• Minocycline (Systemic)

May enhance the CNS depressant effect of CNS Depressants.

• Monoamine Oxidase Inhibitors

Opioid Agonists may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

The common side effects of Pentazocin include the following

• Common side effects

Feeling very tired, lightheadedness, drowsiness, mood changes, headache, upset stomach, constipation, stomach pain, rash, difficulty urinating.

• Rare side effects

Difficulty breathing, changes in heartbeat, agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea, nausea, vomiting, loss of appetite, weakness, or dizziness, inability to get or keep an erection, irregular menstruation, decreased sexual desire, fainting.

• Pregnancy

Pregnancy Category C

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with Pentazocin in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, pentazocine administered subcutaneously to pregnant hamsters during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 4.4 times the maximum daily dose. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

• Nursing Mothers

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Pentazocin and any potential adverse effects on the breast-fed infant from Pentazocin or from the underlying maternal condition.

• Pediatric Use

The safety and efficacy of Pentazocin as preoperative or preanesthetic medication have been established in pediatric patients 1 to 16 years of age. Use of Pentazocin in these age groups is supported by evidence from adequate and controlled studies in adults with additional data from published controlled trials in pediatric patients. The safety and efficacy of Pentazocin as a premedication for sedation have not been established in pediatric patients less than one year old. Information on the safety profile of Pentazocin as a postoperative analgesic in children less than 16 years is limited.

• Geriatric Use

Pentazocine is metabolized in the liver and excreted primarily in the urine. Patients with impaired renal or hepatic function may have slower elimination of the drug, and the risk of adverse reactions to this drug may be greater in these patients. Elderly patients (aged 65 years or older) may have increased sensitivity to pentazocine. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were coadministered with other agents that depress respiration. Titrate the dosage of Pentazocin slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression. Pentazocine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Symptoms: Respiratory depression, hallucinations, seizures, hypotension, hypertension, tachycardia. In severe cases, circulatory failure, and coma.

Management: Symptomatic and supportive treatment. Ensure adequate ventilation and protect the airways in consideration of gastric lavage and prevention of aspiration vomitus. Induce vomiting if patient is awake. May administer naloxone IV 0.4-2 mg, repeat every 2-3 minutes as necessary up to a total of 10 mg.

• Pharmacodynamic

Pentazocine is a potent analgesic which when administered orally in a 50 mg dose appears equivalent in analgesic effect to 60 mg (1 grain) of codeine. Onset of significant analgesia usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. Pentazocine weakly antagonizes the analgesic effects of morphine and meperidine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has sedative activity.

• Pharmacokinetics

Absorption

Pentazocin is absorbed well from the gastrointestinal tract. Time taken to reach peak plasma concentration is approximately 1-3 hours.

Distribution

Pentazocin crosses placenta. The Plasma protein binding is about 60%.

Metabolism and Excretion

Pentazocin is primarily Metabolized in the liver via oxidative and glucuronide conjugation pathways; undergoes extensive first-pass metabolism. Mainly excreted Via urine (small amounts as unchanged drug).

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/016194s079s080lbl.pdf
• https://www.rxlist.com/pentazocine-naloxone/generic-drug.htm#what_are_dosages_of_pentazocine-naloxone
• https://medlineplus.gov/druginfo/meds/a601092.html#:~:text=Pentazocine is used to relieve,nervous system respond to pain.
• https://www.uptodate.com/contents/pentazocine-united-states-not-available-drug-information#F208007
• https://go.drugbank.com/drugs/DB00652