NALOXONE MYLAN

Tablets, USP contain pentazocine hydrochloride, USP, a partial opioid agonist, equivalent to 50 mg base and is a member of the benzazocine series (also known as the benzomorphan series), and naloxone hydrochloride, USP, an opioid antagonist equivalent to 0.5 mg base.

Tablets, USP are an analgesic for oral administration.

Chemically, pentazocine hydrochloride, USP is (2 R ,6 R ,11 R *)-1,2,3,4,5,6-Hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol hydrochloride, a white, crystalline substance soluble in acidic aqueous solutions, and has the following structural formula: Chemically, naloxone hydrochloride, USP is Morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2 - propenyl)-, hydrochloride, (5α)-.

It is a slightly off-white powder, and is soluble in water and dilute acids, and has the following structural formula: Inactive Ingredients: colloidal silicon dioxide, dibasic calcium phosphate, D&C Yellow No. 10, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate and pregelatinized starch.

Tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration, and persist over the course of therapy, reserve opioid analgesics, including Pentazocine and Naloxone Tablets for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

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Pentazocine is a mixed agonist-antagonist at opioid receptors.

Pentazocine is a partial agonist at the mu opioid receptor and an agonist at the kappa opioid receptor.

Naloxone is an opioid antagonist.

Pharmacodynamics Effects on the Central Nervous System Pentazocine produces respiratory depression by direct action on brain stem respiratory centers.

The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.

Pentazocine causes miosis, even in total darkness.

Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings).

Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.

Effects on the Gastrointestinal Tract and Other Smooth Muscle Pentazocine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum.

Digestion of food in the small intestine is delayed and propulsive contractions are decreased.

Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation.

Other opioid.

• induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED).

Pentazocine produces peripheral vasodilation which may result in orthostatic hypotension or syncope.

Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.

Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans.

They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.

Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility.

The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date.

Opioids have been shown to have a variety of effects on components of the immune system.

The clinical significance of these findings is unknown.

Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration–Efficacy Relationships The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonist.

The minimum effective analgesic concentration of pentazocine for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome, and/or the development of analgesic tolerance.

Concentration–Adverse Reaction Relationships There is a relationship between increasing pentazocine plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression.

In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions.

Pentazocine weakly antagonizes the analgesic effects of morphine, meperidine, and phenazocine; 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.

Naloxone when administered orally at 0.5 mg has no pharmacologic activity.

Naloxone hydrochloride administered parenterally at the same dose is an antagonist to pentazocine and a pure antagonist to narcotic analgesics.

Tablets are a potent analgesic when administered orally.

However, the presence of naloxone in Pentazocine and Naloxone Tablets is intended to prevent the effect of pentazocine if the product is misused by injection.

Studies in animals indicate that the presence of naloxone does not affect pentazocine analgesia when the combination is given orally.

If the combination is given by injection the action of pentazocine is neutralized.

Onset of significant analgesia usually occurs between and 30 minutes after oral administration, and duration of action is usually three hours or longer.

Pentazocine is well absorbed from the gastrointestinal tract.

Concentrations in plasma coincide closely with the onset, duration, and intensity of analgesia.

The time to mean peak concentration in 24 normal volunteers was 1.7 hours (range 0.5 to 4 hours) after oral administration and the mean plasma elimination half-life was 3.6 hours (range 1.5 to 10 hours).

Pentazocine is metabolized in the liver and excreted primarily in the urine.

The products of the oxidation of the terminal methyl groups and glucuronide conjugates are excreted by the kidney.

Elimination of approximately 60% of the total dose occurs within 24 hours.

Pentazocine passes into the fetal circulation.

Mechanism of action

Naloxone is a pure and specific morphineomimetic antagonist with no agonistic effect.

When injected to subjects who have received morphineomimetic agents, naloxone antagonizes their effects (respiratory depression, myosis, analgesia).

Its action depends on the dose, the power of the morphineomimetic to antagonize and the interval separating the injections from the two products.

Administered alone, it is without any specific pharmacological properties.

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Pulmonary edema.

Clinical Presentation Acute overdose with Pentazocine and Naloxone Tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death.

Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication.

For pentazocine alone in single doses above 60 mg there have been reports of the occurrence of nalorphine-like psychotomimetic effects such as anxiety, nightmares, strange thoughts, and hallucinations.

Somnolence, marked respiratory depression associated with hypertension and tachycardia have also resulted as have seizures, hypotension, dizziness, nausea, vomiting, lethargy, and paresthesias.

The respiratory depression is antagonized by naloxone.

Circulatory failure and deepening coma may occur in more severe cases, particularly in patients who have also ingested other CNS depressants such as alcohol, sedative/hypnotics, or antihistamines." Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed.

Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated.

Cardiac arrest or arrhythmias will require advanced life-support measures.

For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene.

As pentazocine is a mixed opioid agonist/antagonist, larger doses of naloxone or nalmefene may be needed to reverse the effects of an overdose.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome.

The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered.

If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

Addiction, Abuse, and Misuse Pentazocine and Naloxone Tablets contain pentazocine, a Schedule IV controlled substance.

As an opioid, Pentazocine and Naloxone Tablets expose users to the risks of addiction, abuse, and misuse.

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Pentazocine and Naloxone Tablets.

Addiction can occur at recommended dosages and if the drug is misused or abused.

The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy.

In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use.

Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing Pentazocine and Naloxone Tablets, and reassess all patients receiving Pentazocine and Naloxone Tablets for the development of these behaviors and conditions.

Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).

The potential for these risks should not, however, prevent the proper management of pain in any given patient.

Patients at increased risk may be prescribed opioids such as Pentazocine and Naloxone Tablets, but use in such patients necessitates intensive counseling about the risks and proper use of Pentazocine and Naloxone Tablets along with frequent reevaluation for signs of addiction, abuse, and misuse.

Consider prescribing an opioid overdose reversal agent.

Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use.

Consider these risks when prescribing or dispensing Pentazocine and Naloxone Tablets.

Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and proper disposal of unused drug.

Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.

Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.

Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status.

Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Pentazocine and Naloxone Tablets, the risk is greatest during the initiation of therapy or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of Pentazocine and Naloxone Tablets are essential.

Tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

Accidental ingestion of even one dose of Pentazocine and Naloxone Tablets, especially by children, can result in respiratory depression and death due to an overdose of pentazocine.

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose.

Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene).

Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.

The presence of risk factors for overdose should not prevent the management of pain in any patient.

Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).

There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics.

Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.

Educate patients and caregivers on how to recognize respiratory depression, and how to use an opioid overdose reversal agent for the emergency treatment of opioid overdose.

Emphasize the importance of calling 911 or getting emergency medical help, even if an opioid overdose reversal agent is administered.

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Pentazocine and Naloxone Tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non - benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids, other opioids).

Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone.

Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use.

In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response.

If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response.

Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation).

If concomitant use is warranted, consider prescribing an opioid overdose reversal agent opioid overdose.

Advise both patients and caregivers about the risks of respiratory depression and sedation when Pentazocine and Naloxone Tablets is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).

Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined.

Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

Neonatal Opioid Withdrawal Syndrome NOWS Use of Pentazocine and Naloxone Tablets for an extended period of time during pregnancy can result in withdrawal in the neonate.

Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.

Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly.

Advise pregnant women using opioids for an extended period of time of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Opioid Analgesic Risk Evaluation and Mitigation

Strategy (REMS) To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products.

Under the requirements of the

REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers.

Healthcare providers are strongly encouraged to do all of the following: Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.

Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed.

Guide (PCG) can be obtained at this link: Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.

Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.

To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 800-503-0784, or log on to The FDA Blueprint can be found at.

Opioid Induced Hyperalgesia and Allodynia Opioid-Induced

Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain.

This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect.

Symptoms of

OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia).

These symptoms may suggest

OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.

Cases of

OIH have been reported, both with short-term and longer-term use of opioid analgesics.

Though the mechanism of

OIH is not fully understood, multiple biochemical pathways have been implicated.

Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia.

If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation (safely switching the patient to a different opioid moiety) .

Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of Pentazocine and Naloxone Tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Pentazocine and Naloxone Tablets are contraindicated in patients with: Significant respiratory depression Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.

Patients with known or suspected gastrointestinal obstruction, including paralytic ileus Patients with hypersensitivity to either pentazocine, naloxone, or any of the formulation excipients (e.g., anaphylaxis) .

Important Dosage and Administration Instructions Pentazocine and Naloxone Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals.

Reserve titration to higher doses of Pentazocine and Naloxone Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.

Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic.

Clinical guidelines on opioid prescribing for some acute pain conditions are available.

There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors.

Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse.

Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Pentazocine and Naloxone Tablets.

Consider this risk when selecting an initial dose and when making dose adjustments.

Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene).

Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.

The presence of risk factors for overdose should not prevent the management of pain in any patient.

Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).

There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics.

Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.

Initial Dosage Use of Pentazocine and Naloxone Tablets as the First Opioid Analgesic Initiate treatment with Pentazocine and Naloxone Tablets, USP in a dosing range of 1 tablet every to 4 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia.

Titrate the dose based upon the individual patient's response to their initial dose of Pentazocine and Naloxone Tablets.

This may be increased to 2 tablets when needed.

Total daily dosage should not exceed 12 tablets.

Conversion from Other Opioids to Pentazocine and Naloxone Tablets There is inter-patient variability in the potency of opioid drugs and opioid formulations.

Therefore, a conservative approach is advised when determining the total daily dosage of Pentazocine and Naloxone Tablets.

It is safer to underestimate a patient's 24-hour Pentazocine and Naloxone Tablets dosage than to overestimate the 24-hour Pentazocine and Naloxone Tablets dosage and manage an adverse reaction due to overdose.

Titration and Maintenance of Therapy Individually titrate Pentazocine and Naloxone Tablets to a dose that provides adequate analgesia and minimizes adverse reactions.

Continually reevaluate patients receiving Pentazocine and Naloxone Tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as assessing for the development of addiction, abuse, or misuse.

Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the Pentazocine and Naloxone Tablets dosage.

If after increasing the dosage, unacceptable opioid.

• related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage.

Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Safe Reduction or Discontinuation of Pentazocine and Naloxone Tablets Do not rapidly reduce or abruptly discontinue Pentazocine and Naloxone Tablets in patients who may be physically dependent on opioids.

Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking Pentazocine and Naloxone Tablets, there are a variety of factors that should be considered, including the total daily dose of opioid (including Pentazocine and Naloxone Tablets) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.

It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic.

When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder.

Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder.

Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients.

Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually.

For patients on Pentazocine and Naloxone

Tablets who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every to 4 weeks.

Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper.

Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge.

Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis.

Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper.

In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper.

A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic.

USP are light yellow, capsule shaped tablets debossed "NL" on left side and "680" on the right side of the bisect and plain on the other side, supplied in bottles of and 500.

Bottles of 100 (NDC 43386-680-01).

Bottles of 500 (NDC 43386-680-05).

Store at 20° to 25°C (68° to 77°F) .

Tablets securely and dispose of properly.

Dispense in a tight, light-resistant container as defined in the USP.

LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc.

Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome.

There are no available data with Pentazocine and Naloxone Tablets in pregnant women 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 2.6 times the maximum daily dose (MDD).

In pregnant rats administered pentazocine:naloxone during organogenesis, there were increased incidences of resorptions and extra ribs at 0.2 times the MDD.

There was no evidence of malformations in rats or rabbits.

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.

Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight.

The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.

Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly.

Safety and effectiveness in pediatric patients below the age of 12 years have not been established.

Elderly patients (aged 65 years or older) may have increased sensitivity to Pentazocine and Naloxone Tablets.

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 co-administered with other agents that depress respiration.

Titrate the dosage of Pentazocine and Naloxone Tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression.

Pentazocine and

Naloxone are 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 regularly evaluate renal function.