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Pentazocine Lactate

Class: Opiate Partial Agonists
Note: This monograph also contains information on Pentazocine Hydrochloride
VA Class: CN101
CAS Number: 64024-15-3
Brands: Talwin

Medically reviewed on November 13, 2017.

Warning

    Concomitant Use with Benzodiazepines or Other CNS Depressants
  • Concomitant use of opiates with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.416 417 418 700 701 702 703

  • Reserve concomitant use of opiate analgesics and benzodiazepines or other CNS depressants for patients in whom alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy and monitor closely for respiratory depression and sedation.700 703 (See Specific Drugs and Laboratory Tests under Interactions.)

Introduction

Analgesic; synthetic opiate partial agonist.a

Uses for Pentazocine Lactate

Pain

Relief of moderate to severe paina b c such as that associated with acute and chronic medical disorders including cancer, orthopedic problems, renal or biliary colic, and dental surgery.a

Preoperative sedation and analgesia and as an adjunct to surgical anesthesia.a c

Obstetric analgesia during labor.a c

Oral dosage form reformulated to contain small amount of naloxone hydrochloride (opiate antagonist) to potentially eliminate misuse via parenteral injection by opiate addicts and drug abusers.a b Naloxone is inactive when administered orally in the amount (0.5 mg) present in the oral formulation and does not affect the efficacy of pentazocine when administered orally.a b

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.431 432 433 435 Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.411 431 434 435 Optimize concomitant use of other appropriate therapies.432 434 435 (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

Generally use opiates for management of chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing410 411 412 413 ) that is not associated with active cancer treatment, palliative care, or end-of-life care only if other appropriate nonpharmacologic and nonopiate pharmacologic strategies have been ineffective and expected benefits for both pain relief and functional improvement are anticipated to outweigh risks.411 412 413 414 422 429

If used for chronic pain, opiate analgesics should be part of an integrated approach that also includes appropriate nonpharmacologic modalities (e.g., cognitive-behavioral therapy, relaxation techniques, biofeedback, functional restoration, exercise therapy, certain interventional procedures) and other appropriate pharmacologic therapies (e.g., nonopiate analgesics, analgesic adjuncts such as selected anticonvulsants and antidepressants for certain neuropathic pain conditions).411 412 413 422 429

Available evidence insufficient to determine whether long-term opiate therapy for chronic pain results in sustained pain relief or improvements in function and quality of life411 423 431 432 436 or is superior to other pharmacologic or nonpharmacologic treatments.432 Use is associated with serious risks (e.g., opiate use disorder, overdose).411 431 436 (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

Pentazocine Lactate Dosage and Administration

General

  • If pentazocine hydrochloride tablets containing small amount of naloxone hydrochloride are ground up and solubilized for parenteral administration, the naloxone will antagonize the effects of pentazocine and will precipitate withdrawal symptoms in drug abusers who are dependent on opiates.a b

Managing Opiate Therapy for Acute Pain

  • Optimize concomitant use of other appropriate therapies.432 434 435

  • When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.411 431 434 435

  • When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.432

  • For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).411 433 434 435 Do not prescribe larger quantities for use in case pain continues longer than expected;411 432 instead, reevaluate patient if severe acute pain does not remit.411 431 435

  • For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.430 431 432

  • Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.430 431

  • Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.430 432 When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.430 431

Managing Opiate Therapy for Chronic Noncancer Pain

  • Although specific recommendations may vary, common elements in clinical guideline recommendations include risk mitigation strategies, upper dosage thresholds, careful dosage titration, and consideration of risks associated with particular opiates and formulations, coexisting diseases, and concomitant drug therapy.410 411 414 415 423

  • Prior to initiating therapy, thoroughly evaluate patient; assess risk factors for misuse, abuse, and addiction;411 412 413 415 422 429 establish treatment goals (including realistic goals for pain and function); and consider how therapy will be discontinued if benefits do not outweigh risks.411 415

  • Regard initial opiate therapy for chronic noncancer pain as a therapeutic trial that will be continued only if there are clinically meaningful improvements in pain and function that outweigh treatment risks.411 412 413

  • Prior to and periodically during therapy, discuss with patients known risks and realistic benefits and patient and clinician responsibilities for managing therapy.411 412 413 414 415

  • Some experts recommend initiating opiate therapy for chronic noncancer pain with conventional (immediate-release) opiate analgesics prescribed at lowest effective dosage.411 415 Individualize opiate selection, initial dosage, and dosage titration based on patient’s health status, prior opiate use, attainment of therapeutic goals, and predicted or observed harms.412 413

  • Evaluate benefits and harms within 1–4 weeks following initiation of therapy or dosage increase411 413 and reevaluate on ongoing basis (e.g., at least every 3 months411 ) throughout therapy.411 412 413 Document pain intensity and level of functioning and assess progress toward therapeutic goals, presence of adverse effects, and adherence to prescribed therapies.412 413 422 423 Anticipate and manage common adverse effects (e.g., constipation, nausea and vomiting, cognitive and psychomotor impairment).412 413 415 If benefits do not outweigh harms, optimize other therapies and taper opiate to lower dosage or taper and discontinue opiate.411 412 413 415

  • When repeated dosage increases required, evaluate potential causes and reassess relative benefits and risks.412 413 Although evidence is limited, some experts state that opiate rotation may be considered in patients with intolerable adverse effects or inadequate benefit despite dosage increases.412 413 415

  • Higher dosages require particular caution,410 412 415 including more frequent and intensive monitoring or referral to specialist.411 412 413 Greater benefits of high-dose opiates for chronic pain not established in controlled clinical studies; higher dosages associated with increased risks (motor vehicle accidents, overdosage, opiate use disorder).411 415 423 424 425 426

  • CDC states that primary care clinicians should carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily for chronic pain and should avoid dosages equivalent to ≥90 mg of morphine sulfate daily or carefully justify decision to prescribe such dosages.411 Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.423 431 Some states have established opiate dosage thresholds (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with specialist is mandated or recommended)411 420 421 423 or have mandated risk-management strategies (e.g., review of state prescription drug monitoring program [PDMP] data prior to prescribing).411 419 423

  • Recommended strategies for managing risks include written treatment agreements or plans (e.g., “contracts”), urine drug testing, review of state PDMP data, and risk assessment and monitoring tools.410 411 412 413 414 415 422 423 429

  • Taper and discontinue opiate therapy if patient engages in serious or repeated aberrant drug-related behaviors or drug abuse or diversion.412 413 415 Offer or arrange treatment for patients with opiate use disorder.411 412 413

  • Consider providing concomitant naloxone for patients at increased risk of opiate overdosage (e.g., those with history of overdose or substance use disorder, those receiving ≥50 mg of morphine sulfate [or equivalent] daily, those receiving benzodiazepines concomitantly, those with medical conditions that could increase sensitivity to opiate effects).411 431

Administration

Administer orally or by IV, IM, or sub-Q injection.b c

Oral Administration

Oral administration is preferable to parenteral administration for chronic therapy.a

IV Administration

For drug compatibility information, see Compatibility under Stability.

IM or Sub-Q Administration

Rotation of injection sites is essential.c

Administer sub-Q only when necessary, because of possible severe tissue damage at the injection site.c

Dosage

Available as pentazocine lactate (injection); dosage expressed in terms of pentazocine.a c Also available as pentazocine and naloxone hydrochlorides (tablets); dosage expressed in terms of the bases.100 101

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.411 413 431 432 435

Adjust dosage according to severity of pain, physical status of the patient, and other drugs that the patient is receiving.a

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.700 703 (See Specific Drugs and Laboratory Tests under Interactions.)

Pediatric Patients

Pain
Preoperative Sedation
IM

Children 1–16 years of age: 0.5 mg/kg.c

Adults

Pain
Oral

Initially, 50 mg every 3–4 hours.a b Increase dosage to 100 mg when needed (maximum 600 mg daily).a b

IV, IM, or Sub-Q

Initially, 30 mg; may repeat dose every 3–4 hours as necessary.a c

Obstetric Analgesia
IV

20 mg IV when contractions become regular; may repeat dose 2 or 3 times at intervals of 2–3 hours as needed.a c

IM

30 mg IM as a single dose.a c

Prescribing Limits

Adults

Pain

For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for the expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).411 433 434 435

CDC recommends that primary care clinicians carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily for chronic pain and avoid dosages equivalent to ≥90 mg of morphine sulfate daily or carefully justify their decision to prescribe such dosages.411 Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.423 431

Some states have set prescribing limits for opiate analgesics (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with a specialist is mandated or recommended).411 420 421 423

Oral

Maximum 600 mg daily.b

IV

Maximum 30 mg as a single dose; maximum 360 mg daily.c

IM

Maximum 60 mg as a single dose; maximum 360 mg daily.c

Sub-Q

Maximum 60 mg as a single dose; maximum 360 mg daily.c

Special Populations

Hepatic Impairment

Doses and/or frequency of administration may need to be decreased, particularly when administered orally, in patients with hepatic impairment (e.g., cirrhosis).144 145 155

Geriatric Patients

Cautious dosage selection recommended; initiate therapy at the lower end of the usual range.b c

Cautions for Pentazocine Lactate

Contraindications

  • Known hypersensitivity to pentazocine or any ingredient in the formulation.b c d

Warnings/Precautions

Warnings

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence.100 109 124 125 126 127 128 129 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 186

Prescribe cautiously for patients who are emotionally unstable or have a history of opiate abuse; closely supervise these patients when therapy for more than 4 or 5 days is contemplated.a Avoid unnecessary increases in dosage or frequency of administration; avoid use in anticipation of pain.a

If tablets are ground up and solubilized for parenteral administration, the naloxone will antagonize the effects of pentazocine and can precipitate withdrawal in individuals physically dependent on opiates.100 106 161 However, since naloxone is inactive when administered orally in the amount present in the tablets, the tablets are still subject to misuse and abuse by the oral route.100

Pentazocine has been abused in combination with tripelennamine (no longer commercially available in US) (T’s and blues) via parenteral injection by opiate addicts and drug abusers in an attempt to provide effects similar to those of IV heroin.106 109 110 111 112 113 114 115 116 117 118 119 130 186

Respiratory Effects

Possible respiratory depression (decreased rate and depth of respiration), dyspnea, and laryngospasm.a b

Use with caution and in low doses in patients with impaired respiration caused by other drugs, uremia, or severe infection and in patients with severely limited respiratory reserve, bronchial asthma or other obstructive respiratory conditions, or cyanosis.b c

Pentazocine-induced respiratory depression can be reversed by naloxone.b

Consider offering naloxone when opiate analgesics are prescribed for patients at increased risk of opiate overdosage (e.g., those with history of overdose or substance use disorder, those receiving ≥50 mg of morphine sulfate [or equivalent] daily, those receiving benzodiazepines concomitantly, those with medical conditions that could increase sensitivity to opiates).411 431

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiate agonists or opiate partial agonists, including pentazocine, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiates, alcohol) may result in profound sedation, respiratory depression, coma, and death.416 417 418 700 701 702 703 Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.416 417 418 435 700 701

Reserve concomitant use of pentazocine and other CNS depressants for patients in whom alternative treatment options are inadequate.700 703 (See Specific Drugs and Laboratory Tests under Interactions.)

Local Effects

Possible ulceration and severe sclerosis of the skin, subcutaneous tissues, and underlying muscle following repeated injection.c Rotation of injection sites is essential.c

Patients Dependent on Opiates

Partial opiate antagonist.b c Use with caution in patients who have been chronically receiving opiates (including methadone); pentazocine does not suppress the abstinence syndrome in these patients; high doses may precipitate withdrawal symptoms.b c

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.b c

Concurrent use of other CNS depressants may potentiate CNS depressionb c and may result in profound sedation, respiratory depression, coma, or death.700 703 (See Concomitant Use with Benzodiazepines or Other CNS Depressants under Cautions.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.400 Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.400

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.400 If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.400 In some patients, switching to a different opiate improved symptoms.400

Withdrawal Effects

Abrupt discontinuance after prolonged use may result in withdrawal symptoms (e.g., abdominal cramps, vomiting, increased temperature, sweating, chills, restlessness, anxiety, lethargy, rhinorrhea, sneezing, lacrimation).166 169 172 173 174 175 176 181 182 184 185 Reinstitution of parenteral pentazocine followed by gradual withdrawal of the drug may ameliorate withdrawal symptoms, if necessary.c

Manufacturer states that substitution of methadone or other opiates to treat pentazocine abstinence syndrome should be avoided;184 however, opiates occasionally have been used in the management of pentazocine withdrawal;169 172 174 182 183 benzodiazepines also have been used in a limited number of individuals.181

Head Injury and Increased Intracranial Pressure

Potential for elevation of CSF pressure as a result of vasodilation following carbon dioxide retention.a c Opiate effects may obscure the existence, extent, or course of intracranial pathology.b c Use in patients with head injury, other intracranial lesions, or preexisting elevation in intracranial pressure only if the potential benefits justify the possible risks.a b c

Acute CNS Manifestations

Hallucinations (usually visual), disorientation, and confusion have occurred following therapeutic doses but usually have cleared spontaneously within several hours.b c

If such symptoms occur, closely observe the patient and check vital signs.b c Caution if pentazocine is reinstated, since acute CNS reactions may recur.b c

Acute MI

Possible increased systemic and pulmonary arterial pressure and systemic vascular resistance with IV administration in patients with acute MI.c Administer IV with caution in patients with acute MI accompanied by hypertension or left ventricular failure.c

Administer oral pentazocine with caution in patients with acute MI accompanied by nausea and vomiting.b

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sodium metabisulfite or acetone sodium bisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.c

General Precautions

Biliary Tract Surgery

Possible spasm of Oddi’s sphincter; use with caution in patients about to undergo biliary tract surgery.b c

Seizures

Possible occurrence of seizures following administration in seizure-prone patients.b c Use with caution in such patients.b c

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;400 401 402 403 404 causality not established.400 Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.400 Perform appropriate laboratory testing in patients with manifestations of hypogonadism.400

Specific Populations

Pregnancy

Category C.b

Safe use in pregnant women (except during labor) not established.b c Should not be administered to women who are pregnant unless potential benefits outweigh possible risks to fetus.b c Possible abstinence (withdrawal) syndrome in neonates after prolonged maternal use during pregnancy.100 150 151 152 153 154

Following parenteral administration during labor, alterations (usually increases) in rate and strength of uterine contractions may occur.a

Respiratory depression and transient apnea may occur in neonates when administered during labor and delivery;a use with caution in women delivering premature infants.b c

Lactation

Not known whether pentazocine is distributed into milk; use with caution in nursing women.b

Pediatric Use

Safety and efficacy of oral pentazocine not established in children <12 years of age.a b

Safety and efficacy of parenteral pentazocine for preoperative sedation not established in infants <1 year of age.c

Geriatric Use

Possible increased sensitivity to pentazocine in some geriatric individuals.c

Insufficient experience with pentazocine tablets in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.b

Use with caution due to the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.b c May be useful to monitor renal function.c

Select dosage with caution.b c (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution.b c Extensive liver disease may predispose to greater incidence or severity of adverse effects than would be expected from usual doses, probably as a result of decreased hepatic metabolism of the drug.b c

Renal Impairment

Use with caution.b c

Common Adverse Effects

Dizziness, lightheadedness, euphoria, sedation, nausea.a

Interactions for Pentazocine Lactate

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.400 May occur at usual dosages.400 Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.400 (See Advice to Patients.)

If concomitant use of other serotonergic drugs is warranted, monitor patients for serotonin syndrome, particularly during initiation of therapy and dosage increases.400

If serotonin syndrome is suspected, discontinue pentazocine, other opiate therapy, and/or any concurrently administered serotonergic agents.400

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), SNRIs (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine), tricyclic antidepressants (TCAs), mirtazapine, nefazodone, trazodone, vilazodone

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, the antidepressant, and/or any concurrently administered opiates or serotonergic agents400

Antiemetics, 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, the 5-HT3 receptor antagonist, and/or any concurrently administered opiates or serotonergic agents400

Antipsychotics (e.g., aripiprazole, asenapine, cariprazine, chlorpromazine, clozapine, fluphenazine, haloperidol, iloperidone, loxapine, lurasidone, molindone, olanzapine, paliperidone, perphenazine, pimavanserin, quetiapine, risperidone, thioridazine, thiothixene, trifluoperazine, ziprasidone)

Risk of profound sedation, respiratory depression, coma, or death700 703

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving pentazocine, initiate antipsychotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving an antipsychotic, initiate pentazocine, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Benzodiazepines (e.g., alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, triazolam)

Risk of profound sedation, respiratory depression, coma, or death700 703

Whenever possible, avoid concomitant use410 411 415 435

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving pentazocine, initiate benzodiazepine, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a benzodiazepine, initiate pentazocine, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Consider offering naloxone to patients receiving opiates and benzodiazepines concomitantly411 431

Buspirone

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, buspirone, and/or any concurrently administered opiates or serotonergic agents400

CNS depressants (e.g., other opiates, general anesthetics, phenothiazines or other tranquilizers, anxiolytics, alcohol)

Possible additive effects;b c increased risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving pentazocine, initiate CNS depressant, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a CNS depressant, initiate pentazocine, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Avoid alcohol use700

Dextromethorphan

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, dextromethorphan, and/or any concurrently administered opiates or serotonergic agents400

5-HT1 receptor agonists (triptans; e.g., almotriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, the triptan, and/or any concurrently administered opiates or serotonergic agents400

Lithium

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, lithium, and/or any concurrently administered opiates or serotonergic agents400

MAO inhibitors (e.g., isocarboxazid, linezolid, methylene blue, phenelzine, selegiline, tranylcypromine)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, the MAO inhibitor, and/or any concurrently administered opiates or serotonergic agents400

Sedative/hypnotic agents (e.g., butabarbital, eszopiclone, pentobarbital, ramelteon, secobarbital, suvorexant, zaleplon, zolpidem)

Risk of profound sedation, respiratory depression, coma, or death700 703

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving pentazocine, initiate sedative/hypnotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a sedative/hypnotic, initiate pentazocine, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Skeletal muscle relaxants (e.g., baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, tizanidine)

Risk of profound sedation, respiratory depression, coma, or death700 703

Cyclobenzaprine: Increased risk of adverse effects (e.g., seizures, serotonin syndrome)400

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving pentazocine, initiate skeletal muscle relaxant, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a skeletal muscle relaxant, initiate pentazocine, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Cyclobenzaprine: If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, cyclobenzaprine, and/or any concurrently administered opiates or serotonergic agents400

St. John’s wort (Hypericum perforatum)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, St. John’s wort, and/or any concurrently administered opiates or serotonergic agents400

Tests for urinary 17-hydroxycorticosteroids

Possible decrease in urinary 17-hydroxycorticosteroid determinations (Porter-Silber reaction)a

Clinical importance not establisheda

Tryptophan

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue pentazocine, tryptophan, and/or any concurrently administered opiates or serotonergic agents400

Pentazocine Lactate Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tractb and from IM and sub-Q injection sites.a

Undergoes first-pass metabolism following oral administration, with <20% of an oral dose reaching systemic circulation as unchanged drug.a

Onset

Following oral administration, onset of analgesia occurs within 15–30 minutes; peak analgesia occurs within 1–3 hours.a b

Following IM or sub-Q injection, onset of analgesia occurs within 15–20 minutes; peak analgesia occurs within about 1 hour.a c

Following IV administration, onset of analgesia occurs within 2–3 minutes; peak analgesia occurs within 15 minutes.a c

Duration

Following oral administration, duration of analgesia is ≥3 hours.b

Following IM or sub-Q injection, duration of analgesia is about 2 hours; following IV administration, duration is about 1 hour.a

Special Populations

In patients with hepatic dysfunction, oral bioavailability may be substantially increased; about 60–70% of an oral dose is reportedly absorbed unchanged in individuals with cirrhosis.144 145

Distribution

Extent

Widely distributed in the body.a

Crosses the placenta; neonatal serum concentrations reported to average about 65% of maternal concentrations at delivery.a b

Not known whether pentazocine is distributed into milk.b

Plasma Protein Binding

About 60%.a

Elimination

Metabolism

Metabolized in the liver.b

Elimination Route

Excreted principally in urine.b Less unchanged drug appears to be excreted in urine after oral administration than after IV administration.a

Half-life

2–3 hours.b

Special Populations

In patients with hepatic impairment, clearance may be decreased and elimination half-life prolonged.144 145 155

In geriatric patients, elimination half-life may be prolonged and systemic exposure to pentazocine increased.c

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).b

Parenteral

Injection

15–30°C.c

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Drug Compatibility

Admixture CompatibilityHID

Incompatible

Aminophylline

Amobarbital sodium

Pentobarbital sodium

Phenobarbital sodium

Sodium bicarbonate

Y-site CompatibilityHID

Compatible

Heparin sodium

Hydrocortisone sodium succinate

Potassium chloride

Vitamin B complex with C

Incompatible

Nafcillin sodium

Actions

  • Believed to be a competitive antagonist at μ opiate receptors and an agonist at κ and Σ opiate receptors.a

  • Analgesic and respiratory depressant activity apparently results mainly from the l-isomer.a

  • Produces respiratory depression, sedation, miosis, and antitussive effects.a

  • In low doses (15 mg IM), pentazocine inhibits GI motility and slows the rate of gastric emptying; higher doses (30–45 mg) reportedly increase intestinal transit time and produce less elevation of biliary pressure than equianalgesic doses of morphine.a

Advice to Patients

  • Potential for pentazocine to impair mental alertness or physical coordination; do not drive or operate machinery until effects on individual are known.b

  • Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.700 703 Importance of informing patients that pentazocine should not be combined with alcohol.700 b

  • Importance of taking exactly as prescribed; do not exceed the recommended dosage.b

  • Potential risk of serotonin syndrome with concurrent use of pentazocine and other serotonergic agents.400 Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.400

  • Potential risk of adrenal insufficiency.400 Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.400

  • Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.400 Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.400

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and alcohol consumption.b

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.b

  • Importance of advising patients of other important precautionary information.b c (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as schedule IV (C-IV) drugs. May be subject to more stringent control in some states.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pentazocine and Naloxone Hydrochlorides

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

Pentazocine Hydrochloride 50 mg (of pentazocine) and Naloxone Hydrochloride 0.5 mg (of naloxone)*

Pentazocine and Naloxone Hydrochlorides Tablets ( C-IV)

Pentazocine Lactate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

30 mg (of pentazocine) per mL

Talwin ( C-IV)

Hospira

AHFS DI Essentials. © Copyright 2018, Selected Revisions November 13, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

100. Talwin NX prescribing information. In: Huff BB, ed. Physicians’ desk reference. 39th ed. Oradell, NJ: Medical Economics Company Inc; 1985:2230-2.

101. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Suppl 2. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1985:1876-7.

102. Hoppin EC, Greenberg BR, Walter RM. Agranulocytosis secondary to pentazocine therapy. Arch Intern Med. 1978; 138:533-4. [PubMed 637634]

103. Marks A, Abramson N. Pentazocine and agranulocytosis. Ann Intern Med. 1980; 92:433. [PubMed 7356240]

104. Haibach H, Yesus YW, Doggett JJ. Pentazocine-induced agranulocytosis. Can Med Assoc J. 1984; 130:1165-6. [PubMed 6713337]

105. Sheehan M, Hyland RH, Norman C. Pentazocine-induced agranulocytosis. Can Med Assoc J. 1985; 132:1401. [PubMed 4005730]

106. Reinhart S, Barrett SM. An acute hypertensive response after intravenous use of a new pentazocine formulation. Ann Emerg Med. 1985; 14:591-3. [PubMed 3994086]

107. Adams EM, Horowitz HW, Sundstrom WR. Fibrous myopathy in association with pentazocine. Arch Intern Med. 1983; 143:2203-4. [PubMed 6639246]

108. Staritz M, Poralla T, Manns M et al. Pentazocine hampers bile flow. Lancet. 1985; 1:573-4. [PubMed 2857916]

109. Anon. Pentazocine abuse rises—schedule IV status proposed. FDA Drug Bull. 1978; 8:34.

110. Lahmeyer HW, Steingold RG. Pentazocine and tripelennamine: a drug abuse epidemic? Int J Addict. 1980; 15:1219-32.

111. Showalter CV. T’s and blues: abuse of pentazocine and tripelennamine. JAMA. 1980; 224:1224-5.

112. Poklis A. Pentazocine/tripelennamine (T’s and blues) abuse: a five year survey of St. Louis, Missouri. Drug Alcohol Depend. 1982; 10:257-67. [PubMed 7166138]

113. De Bard ML, Jagger JA. T’s and B’s—midwestern heroin substitute. Clin Toxicol. 1981; 18:1117-23. [PubMed 7318393]

114. Itkonen J, Schnoll S, Daghestani A et al. Accelerated development of pulmonary complications due to illicit intravenous use of pentazocine and tripelennamine. Am J Med. 1984; 76:617-22. [PubMed 6711575]

115. Butch AJ, Yokel RA, Sigell LT et al. Abuse and pulmonary complications of injecting pentazocine and tripelennamine tablets. Clin Toxicol. 1979; 14:301-6. [PubMed 455920]

116. Lahmeyer HW, Steingold RG. Medical and psychiatric complications of pentazocine and tripelennamine abuse. J Clin Psychiatry. 1980; 41:275-8. [PubMed 7400105]

117. Caplan LR, Thomas C, Banks G. Central nervous system complications of addiction to T’s and blues. Neurology. 1982; 32:623-8. [PubMed 7201092]

118. Poklis A, Mackell MA. Pentazocine and tripelennamine (T’s and blues) abuse: toxicological findings in 39 cases. J Anal Toxicol. 1982; 6:110-4.

119. Heaney RM, Gotlieb N. Granulocytopenia after intravenous abuse of pentazocine and tripelennamine (“T’s and blues”). South Med J. 1983; 76:654-6. [PubMed 6844971]

120. Burton JF, Zawadzki S, Wetherell HR et al. Mainliners and blue velvet. J Forensic Sci. 1965; 10:466-72. [PubMed 5839798]

121. Zwed JJ. Pulmonary angiothrombosis caused by “blue velvet” addiction. Ann Intern Med. 1970; 73:771-4. [PubMed 5476210]

122. Lerner AM, Oerther FJ. Characteristics and sequelae of paregoric abuse. Ann Intern Med. 1966; 65:1019-30. [PubMed 5923084]

123. Wendt VE, Puro HE, Shapira J et al. Angiothrombotic pulmonary hypertension in addicts. “Blue velvet” addiction. JAMA. 1964; 188:755-7. [PubMed 14122687]

124. Houck RJ, Bailey GL, Daroca PJ Jr et al. Pentazocine abuse: report of a case with pulmonary arterial cellulose granulomas and pulmonary hypertension. Chest. 1980; 77:227-9. [PubMed 7353425]

125. Tomashefski JF Jr, Hirsch CS, Jolly PN. Microcrystalline cellulose pulmonary embolism and granulomatosis: a complication of illicit intravenous injections of pentazocine tablets. Arch Pathol Lab Med. 1981; 105:89-93. [PubMed 6893924]

126. Farber HW, Mathers JAL Jr, Glauser FL. Gallium scans and serum angiotensin converting enzyme levels in talc granulomatosis and lymphocytic interstitial pneumonitis. South Med J. 1980; 73:1663-7. [PubMed 6255609]

127. Farber HW, Falls R, Glauser FL. Transient pulmonary hypertension from the intravenous injection of crushed, suspended pentazocine tablets. Chest. 1981; 80:178-82. [PubMed 7249763]

128. Farber HW, Fairman RP, Glauser FL. Talc granulomatosis: laboratory findings similar to sarcoidosis. Am Rev Respir Dis. 1982; 125:258-61. [PubMed 6278999]

129. Farber H, Glauser FL. The effect of oral hydralazine on the pulmonary hemodynamics of patients with pulmonary foreign body granulomatosis. Chest. 1982; 82:708-12. [PubMed 7140398]

130. Meador KH, Sharon Z, Lewis EJ. Renal amyloidosis and subcutaneous drug abuse. Ann Intern Med. 1979; 91:565-7. [PubMed 484955]

131. Mizutani T, Lewis RA, Gonatas NK. Medial medullary syndrome in a drug abuser. Arch Neurol. 1980; 37:425-8. [PubMed 7387487]

132. AtLee WE Jr. Talc and corn starch emboli in eyes of drug abusers. JAMA. 1972; 219:49-51. [PubMed 5066587]

133. Kresca LJ, Goldberg MF, Jampol LM. Talc emboli and retinal neovascularization in a drug abuser. Am J Ophthalmol. 1979; 87:334-9. [PubMed 434093]

134. Friberg TR, Gragoudas ES, Regan CDJ. Talc emboli and macular ischemia in intravenous drug abuse. Arch Ophthalmol. 1979; 97:1089-91. [PubMed 444139]

135. Schatz H, Drake M. Self-injected retinal emboli. Ophthalmology. 1979; 86:468-83. [PubMed 530595]

136. Shook JE, Kallman MJ, Martin BR et al. Characterization of the interaction of pentazocine and tripelennamine: drug discrimination and mu-receptor binding assay. Pharmacol Biochem Behav. 1984; 21:877-81. [PubMed 6097919]

137. Shannon HE, Su TP. Effects of the combination of tripelennamine and pentazocine at the behavioral and molecular levels. Pharmacol Biochem Behav. 1982; 17:789-95. [PubMed 6294681]

138. Su TP. Possible explanations of “T’s and Blues” interaction: tripelennamine and pentazocine are potent ligands for psychotomimetic sigma-opioid receptor. Fed Proc. 1983; 42:1017.

139. Tagashira E, Kachur JF, Carter WH Jr et al. Pentazocine-tripelennamine (“T’s and Blues”) substitution studies in morphine-dependent rodents. J Pharmacol Exp Ther. 1984; 231:97-101. [PubMed 6541694]

140. Bhargava HN. Mechanism of toxicity and rationale for use of the combination of pentazocine and Pyribenzamine in morphine-dependent subjects. Clin Toxicol. 1981; 18:175-88. [PubMed 7194759]

141. Waller DP, Katz NL, Morris RW. Potentiation of lethality in mice by combinations of pentazocine and tripelennamine. Clin Toxicol. 1980; 16:17-23. [PubMed 7389279]

142. Martin WR. Pharmacology of opioids. Pharmacol Rev. 1983; 35:283-323. [PubMed 6144112]

143. Oh SJ, Rollins JL, Lewis I. Pentazocine-induced fibrous myopathy. JAMA. 1975; 231:271-3. [PubMed 1172732]

144. Pond SM, Tong T, Benowitz NL et al. Enhanced bioavailability of pethidine and pentazocine in patients with cirrhosis of the liver. Aust N Z J Med. 1980; 10:515-9. [PubMed 6937164]

145. Neal EA, Meffin PJ, Gregory PB et al. Enhanced bioavailability and decreased clearance of analgesics in patients with cirrhosis. Gastroenterology. 1979; 77:96-102. [PubMed 447033]

146. Padilla RS, Becker LE, Hoffman H et al. Cutaneous and venous complications of pentazocine abuse. Arch Dermatol. 1979; 115:975-7. [PubMed 464626]

147. Dunn DW, Reynolds J. Neonatal withdrawal symptoms associated with “T’s and blues” (pentazocine and tripelennamine). Am J Dis Child. 1982; 136:644-5. [PubMed 7091098]

148. Chasnoff IJ, Hatcher R, Burns WJ et al. Pentazocine and tripelennamine (T’s and blues): effects on the fetus and neonate. Dev Pharmacol Ther. 1983; 6:162-9. [PubMed 6861602]

149. American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics. 1983; 72:895-902. [PubMed 6139783]

150. Scanlon JW. Pentazocine and neonatal narcotic withdrawal. J Pediatr. 1974; 85:735-6. [PubMed 4213858]

151. Reeds TO. Withdrawal symptoms in a neonate associated with maternal pentazocine abuse. J Pediatr. 1975; 87:324. [PubMed 1151571]

152. Goetz RL, Bain RV. Neonatal withdrawal symptoms associated with maternal use of pentazocine. J Pediatr. 1974; 84:887-8. [PubMed 4275009]

153. Preis O, Choi S, Rudolph N. Pentazocine withdrawal syndrome in the newborn infant. Am J Obstet Gynecol. 1977; 127:205-6. [PubMed 831505]

154. Kopelman AE. Fetal addiction to pentazocine. Pediatrics. 1975; 55:888-9. [PubMed 1134890]

155. Williams RL. Drug administration in hepatic disease. N Engl J Med. 1983; 309:1616-22. [PubMed 6358891]

156. Shannon HE, Su TP. Effects of the combination of tripelennamine and pentazocine at the behavioral and molecular levels. Pharmacol Biochem Behav. 1982; 17:789-95. [PubMed 6294681]

157. Su TP. Possible explanations of “T’s and blues” interaction: tripelennamine and pentazocine are potent ligands for psychotomimetic sigma-opioid receptor. Fed Proc. 1983; 42:1017.

158. Tagashira E, Kachur JF, Carter WH Jr et al. Pentazocine-tripelennamine (“T’s and Blues”) substitution studies in morphine-dependent rodents. J Pharmacol Exp Ther. 1984; 231:97-101. [PubMed 6541694]

159. Bhargava HN. Mechanism of toxicity and rationale for use of the combination of pentazocine and Pyribenzamine in morphine-dependent subjects. Clin Toxicol. 1981; 18:175-88. [PubMed 7194759]

160. Waller DP, Katz NL, Morris RW. Potentiation of lethality in mice by combinations of pentazocine and tripelennamine. Clin Toxicol. 1980; 16:17-23. [PubMed 7389279]

161. C.dtdon C. Talwin 50 reformulated to avert “T’s and blues” abuse. JAMA. 1983; 249:1689.

162. Shekar R, Rice TW, Zierdt CH et al. Outbreak of endocarditis caused by Pseudomonas aeruginosa serotype 011 among pentazocine and tripelennamine abusers in Chicago. J Infect Dis. 1985; 151:203-8. [PubMed 3918121]

163. Botsford KB, Weinstein RA, Nathan CR et al. Selective survival in pentazocine and tripelennamine of Pseudomonas aeruginosa serotype 011 from drug addicts. J Infect Dis. 1985; 151:209-16. [PubMed 3918122]

164. Snyder SH. Drug and neurotransmitter receptors in the brain. Science. 1984; 224:22-31. [PubMed 6322304]

165. Nicol CG. Abuse of pentazocine. Br Med J. 1978; 2:357-8. [PubMed 687923]

166. Waldmann E, Horsfall PAL. Pentazocine addiction: a warning. Br Med J. 1977; 1:642.

167. Kirts TE. Pentazocine abuse. JAMA. 1973; 224:1532. [PubMed 4739966]

168. Halliday WR. Abuse of pentazocine. JAMA. 1973; 223:801. [PubMed 4265252]

169. Schoolar JC, Idanpaan-Heikkila P, Keats AS. Pentazocine addiction? Lancet. 1969; 1:1263. Letter. (IDIS 10705)

170. Finkelstein IS. Pentazocine abuse. JAMA. 1973; 224:249. [PubMed 4739509]

171. Kubicki S. Abuse of pentazocine. Br Med J. 1978; 2:955-6. [PubMed 709150]

172. Raskin NN. Methadone for the pentazocine-dependent patient. N Engl J Med. 1970; 283:1349. [PubMed 5478464]

173. Weber WF, Frome HP. Addiction to pentazocine: report of two cases. JAMA. 1970; 212:1708. [PubMed 5467857]

174. Sandoval RG, Wang RIH. Tolerance and dependence on pentazocine. N Engl J Med. 1969; 280:1391-2. [PubMed 5771364]

175. American Medical Association Council on Drugs. The misuse of pentazocine: its dependence-producing potential. JAMA. 1969; 209:1518-9. [PubMed 5820108]

176. Hart RH. Pentazocine addiction. Lancet. 1969; 2:690. [PubMed 4185426]

177. Hunter R, Ingram IM. Intravenous pentazocine abuse by a nurse. Lancet. 1983; 2:227. [PubMed 6135066]

178. Bailey WJ. Nonmedical use of pentazocine. JAMA. 1979; 242:2392. [PubMed 490845]

179. Ungerleider JT, Lundberg GD, Sunshine I et al. The drug abuse warning network (DAWN) program. Arch Gen Psychiatry. 1980; 37:106-9. [PubMed 7352834]

180. Sandoval RG, Wang RIH. Characteristics of pentazocine dependence in hospitalized patients after naloxone administration. Psychopharmacologia. 1973; 30:205-15. [PubMed 4577443]

181. Swanson DW, Weddige RL, Morse RM. Hospitalized pentazocine abusers. Mayo Clin Proc. 1973; 48:85-93. [PubMed 4689658]

182. Parwatikar S, Gomez H, Knowles RR. Pentazocine dependency. Int J Addict. 1973; 8:87-98. [PubMed 4713708]

183. Fleiss D. Pentazocine-induced fibrous myopathy. JAMA. 1975; 232:1126. [PubMed 1173609]

184. Talwin injection prescribing information. In: Huff BB, ed. Physicians’ desk reference. 39th ed. Oradell, NJ: Medical Economics Company Inc; 1985:2228-9.

185. Jaffe JH, Martin WR. Opioid analgesics and antagonists. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York: The Macmillan Company; 1985:491-531.

186. Pentazocine. In: WHO Expert Committee on Drug Dependence. 25th report. Technical report series 775. Geneva: World Health Organization: 1989:32-6.

400. US Food and Drug Administration. Drug safety communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. Silver Spring, MD; 2016 Mar 22. From FDA website.

401. Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009; 25:170-5. [PubMed 19333165]

402. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL et al. Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer. 2004; 100:851-8. [PubMed 14770444]

403. Abs R, Verhelst J, Maeyaert J et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. 2000; 85:2215-22. [PubMed 10852454]

404. Fraser LA, Morrison D, Morley-Forster P et al. Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women. Exp Clin Endocrinol Diabetes. 2009; 117:38-43. [PubMed 18523930]

410. Nuckols TK, Anderson L, Popescu I et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med. 2014; 160:38-47. [PubMed 24217469]

411. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016; 65:1-49. [PubMed 26987082]

412. Chou R, Fanciullo GJ, Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10:113-30. [PubMed 19187889]

413. Management of Opioid Therapy for Chronic Pain Working Group, US Department of Veterans Affairs and Department of Defense. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. 2010 May.

414. Chou R, Cruciani RA, Fiellin DA et al. Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. J Pain. 2014; 15:321-37. [PubMed 24685458]

415. Manchikanti L, Abdi S, Atluri S et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician. 2012; 15(3 Suppl):S67-116.

416. Park TW, Saitz R, Ganoczy D et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015; 350:h2698. [PubMed 26063215]

417. Jones CM, McAninch JK. Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines. Am J Prev Med. 2015; 49:493-501. [PubMed 26143953]

418. Dasgupta N, Funk MJ, Proescholdbell S et al. Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality. Pain Med. 2016; 17:85-98. [PubMed 26333030]

419. Prescription Drug Monitoring Program Training and Technical Assistance Center (PDMP TTAC). Criteria for mandatory enrollment or query of PDMP. From PDMP TTAC website. Accessed 2016 Sep 14.

420. National Alliance for Model State Drug Laws (NAMSLD). Overview of state pain management and prescribing policies. From NAMSLD webiste. Accessed 2016 Sep 14.

421. Bennett A (Maine Office of Governor). Augusta, ME: 2016 Apr 19. Governor signs major opioid prescribing reform bill. Press release.

422. American Academy of Pain Medicine (AAPM). Use of opioids for the treatment of chronic pain. A statement from the American Academy of Pain Medicine. From AAPM website. 2013 Feb.

423. Franklin GM, American Academy of Neurology. Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology. Neurology. 2014; 83:1277-84. [PubMed 25267983]

424. Dunn KM, Saunders KW, Rutter CM et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010; 152:85-92. [PubMed 20083827]

425. Gomes T, Mamdani MM, Dhalla IA et al. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011; 171:686-91. [PubMed 21482846]

426. Bohnert AS, Valenstein M, Bair MJ et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-21. [PubMed 21467284]

429. Paice JA, Portenoy R, Lacchetti C et al. Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016; 34:3325-45. [PubMed 27458286]

430. Chou R, Gordon DB, de Leon-Casasola OA et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016; 17:131-57. [PubMed 26827847]

431. Washington State Agency Medical Directors' Group (AMDG). Interagency guideline on prescribing opioids for pain, 3rd ed. From Washington State AMDG website. 2015 Jun.

432. Hegmann KT, Weiss MS, Bowden K et al. ACOEM practice guidelines: opioids for treatment of acute, subacute, chronic, and postoperative pain. J Occup Environ Med. 2014; 56:e143-59.

433. Cantrill SV, Brown MD, Carlisle RJ et al. Clinical policy: critical issues in the prescribing of opioids for adult patients in the emergency department. Ann Emerg Med. 2012; 60:499-525. [PubMed 23010181]

434. Thorson D, Biewen P, Bonte B et al, for Institute for Clinical Systems Improvement (ICSI). Acute pain assessment and opioid prescribing protocol. From ICSI website. 2014 Jan.

435. New York City Department of Health and Mental Hygiene. New York City emergency department discharge opioid prescribing guidelines. From NYC Health website. 2013 Jan.

436. Chou R, Deyo R, Devine B et al. The effectiveness and risks of long-term opioid treatment of chronic pain. Evidence report/technology assessment No. 218. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); 2014 Sep.

700. US Food and Drug Administration. Drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Silver Spring, MD; 2016 Aug 31. From FDA website.

701. Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. JAMA. 2013; 309:657-9. [PubMed 23423407]

702. Jones CM, Paulozzi LJ, Mack KA et al. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010. MMWR Morb Mortal Wkly Rep. 2014; 63:881-5. [PubMed 25299603]

703. Hertz S. Letter to manufacturers of opioid analgesics: safety labeling change notification. Silver Spring, MD: US Food and Drug Administration. Accessed 2017 Mar 20.

704. Hospira. Talwin (pentazocine lactate) injection prescribing information. Lake Forest, IL; 2016 Dec.

a. AHFS Drug Information 2004. McEvoy GK, ed. Pentazocine Hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2004.

b. Sanofi-Synthelabous. Talwin Nx (pentazocine and naloxone hydrochlorides) prescribing information. New York, NY; 2003 May.

c. Abbott Laboratories. Talwin (pentazocine lactate) injection prescribing information. North Chicago, IL; 2001 Jan.

d. Sanofi-Synthelabous. Talacen (pentazocine hydrochloride and acetaminophen) prescribing information. New York, NY; 2003 May.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1316-9.

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