LORTAB ELIXIR (Hydrocodone Bitartrate and Acetaminophen Oral Solution), CII

Risk of Medication Errors

Ensure accuracy when prescribing, dispensing, and administering LORTAB ELIXIR. Dosing errors due to confusion between mg and mL, and other hydrocodone bitartrate and acetaminophen oral solution of different concentrations can result in accidental overdose and death [see WARNINGS, DOSAGE AND ADMINISTRATION].

Addiction, Abuse, and Misuse

LORTAB ELIXIR exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing LORTAB ELIXIR, and monitor all patients regularly for the development of these behaviors and conditions [see WARNINGS].

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 REMS for these products [see WARNINGS]. 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

• complete a REMS-compliant education program,
• counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• consider other tools to improve patient, household, and community safety.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of LORTAB ELIXIR. Follow patients for signs of respiratory depression, especially during initiation of LORTAB ELIXIR or following a dose increase [see WARNINGS].

Accidental Ingestion

Accidental ingestion of even one dose of LORTAB ELIXIR, especially by children, can result in a fatal overdose of LORTAB ELIXIR [see WARNINGS].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of LORTAB ELIXIR during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see WARNINGS].

Cytochrome P450 3A4 Interaction

The concomitant use of LORTAB ELIXIR with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. Follow patients receiving LORTAB ELIXIR and any cytochrome P450 3A4 inhibitor or inducer for signs and symptoms of respiratory depression and sedation [see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS; Drug Interactions].

Hepatotoxicity

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product [see WARNINGS, OVERDOSAGE].

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see WARNINGS, PRECAUTIONS; Drug Interactions].

• Reserve concomitant prescribing of LORTAB ELIXIRand benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.

Hydrocodone is a semi-synthetic opioid agonist with relative selectivity for the mu-opioid (μ) receptor, although it can interact with other opioid receptors at higher doses. Hydrocodone acts as a full agonist, binding to and activating opioid receptors at sites in the peri-aquaductal and peri-ventricular gray matter, the ventro-medial medulla and the spinal cord to produce analgesia. The analgesia, as well as the euphoriant, respiratory depressant and physiologic dependence properties of μ agonist opioids like hydrocodone, result principally from agonist action at the μ receptors. The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.

The behavior of the individual components is described below.

Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see WARNINGS], reserve LORTAB ELIXIR for use in patients for whom alternative treatment options (e.g., non-opioid analgesics):

• have not been tolerated, or are not expected to be tolerated
• have not provided adequate analgesia, or are not expected to provide adequate analgesia

Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with hydrocodone bitartrate and acetaminophen oral solutions of different concentrations, when prescribing, dispensing, and administering LORTAB ELIXIR. Ensure that the dose is communicated clearly and dispensed accurately. Always use a calibrated measuring devise when administering LORTAB ELIXIR to ensure the dose is measured and administered accurately.

LORTAB ELIXIR contains hydrocodone, a Schedule II controlled substance. As an opioid, LORTAB ELIXIR exposes users to the risks of addiction, abuse, and misuse [see DRUG ABUSE AND DEPENDENCE].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed LORTAB ELIXIR. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing LORTAB ELIXIR, and monitor all patients receiving LORTAB ELIXIR 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 LORTAB ELIXIR, but use in such patients necessitates intensive counseling about the risks and proper use of LORTAB ELIXIR along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS; Life-Threatening Respiratory Depression, DOSAGE AND ADMINISTRATION; Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose].

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing LORTAB ELIXIR. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see PRECAUTIONS; Information for Patients/Caregivers]. 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.

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. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.
• 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 www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

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 [see OVERDOSAGE]. 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 LORTAB ELIXIR, the risk is greatest during the initiation of therapy or following a dosage increase. Follow patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of LORTAB ELIXIR.

To reduce the risk of respiratory depression, proper dosing and titration of LORTAB ELIXIR are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the LORTAB ELIXIR dosage when converting patients from another opioid product can result in a fatal overdose.

Accidental ingestion of even one dose of LORTAB ELIXIR especially by children, can result in respiratory depression and death due to an overdose of LORTAB ELIXIR.

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 [see PRECAUTIONS; Information for Patients/Caregivers].

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see DOSAGE AND ADMINISTRATION].

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with LORTAB ELIXIR. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see PRECAUTIONS; Information for Patients/Caregivers].

Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of other CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone [see WARNINGS; Addiction, Abuse, and Misuse, Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants; PRECAUTIONS; Information for Patients/Caregivers].

Prolonged use of LORTAB ELIXIR 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 a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see PRECAUTIONS; Information for Patients/Caregivers, Pregnancy].

Concomitant use of LORTAB ELIXIR with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of hydrocodone and prolong opioid adverse reactions, and which may cause potentially fatal respiratory depression [see WARNINGS], particularly when an inhibitor is added after a stable dose of LORTAB ELIXIR is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in LORTAB ELIXIR-treatedpatients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions. When using LORTAB ELIXIR with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in LORTAB ELIXIR-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of LORTAB ELIXIR until stable drug effects are achieved [see PRECAUTIONS; Drug Interactions].

Concomitant use of LORTAB ELIXIR with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease hydrocodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to LORTAB ELIXIR. When using LORTAB ELIXIR with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, follow patients at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see PRECAUTIONS; Drug Interactions].

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of LORTAB ELIXIR with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). 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 [see PRECAUTIONS; Drug Interactions].

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. Follow patients closely for signs and symptoms of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS; Life-Threatening Respiratory Depression, DOSAGE AND ADMINISTRATION; Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose].

Advise both patients and caregivers about the risks of respiratory depression and sedation when LORTAB ELIXIR 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 [see PRECAUTIONS; Drug Interactions, Information for Patients/Caregivers].

The use of LORTAB ELIXIR in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

LORTAB ELIXIR may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see PRECAUTIONS; Drug Interactions]. Follow these patients for signs of hypotension after initiating or titrating the dosage of LORTAB ELIXIR. In patients with circulatory shock LORTAB ELIXIR may cause vasodilatation that can further reduce cardiac output and blood pressure. Avoid the use of LORTAB ELIXIR with circulatory shock.

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.

The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.

Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4,000 milligrams of acetaminophen per day, even if they feel well.

Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

There have been postmarketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue LORTAB ELIXIR immediately and seek medical care if they experience these symptoms. Do not prescribe LORTAB ELIXIR for patients with acetaminophen allergy [see PRECAUTIONS; Information for Patients/Caregivers].

In patients who may be susceptible to the intracranial effects of CO ₂retention (e.g., those with evidence of increased intracranial pressure or brain tumors), LORTAB ELIXIR may reduce respiratory drive, and the resultant CO ₂retention can further increase intracranial pressure. Follow such patients for signs of sedation and respiratory depression, particularly when initiating therapy with LORTAB ELIXIR.

Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of LORTAB ELIXIR in patients with impaired consciousness or coma.

LORTAB ELIXIR is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus.

The administration of LORTAB ELIXIR or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions.

The hydrocodone in LORTAB ELIXIR may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Follow patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

The hydrocodone in LORTAB ELIXIR may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Follow patients with a history of seizure disorders for worsened seizure control during LORTAB ELIXIR therapy.

Do not abruptly discontinue LORTAB ELIXIR in a patient physically dependent on opioids. When discontinuing LORTAB ELIXIR in a physically dependent patient, gradually taper the dosage. Rapid tapering of LORTAB ELIXIR in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see DOSAGE AND ADMINISTRATION, DRUG ABUSE AND DEPENDENCE].

Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including LORTAB ELIXIR. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see PRECAUTIONS; Drug Interactions].

LORTAB ELIXIR may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of LORTAB ELIXIR and know how they will react to the medication [see PRECAUTIONS; Information for Patients/Caregivers].

Advise the patient to read the FDA-approved patient labeling ( Medication Guide).

In patients with severe hepatic or renal disease, effects of therapy should be followed with serial liver and/or renal function tests.

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. LORTAB ELIXIR is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including LORTAB ELIXIR, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Hydrocodone is present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LORTAB ELIXIR and any potential adverse effects on the breastfed infant from LORTAB ELIXIR or from the underlying maternal condition.

Infants exposed to LORTAB ELIXIR through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

The safety and effectiveness of LORTAB ELIXIR in the pediatric population below the age of two years have not been established. Use of LORTAB ELIXIR in the pediatric patients over the age of 2 years is supported by evidence from adequate and well controlled studies of hydrocodone and acetaminophen combination products in adults, along with additional data which support the development of metabolic pathways in children two years of age and over [see DOSAGE AND ADMINISTRATION] for pediatric dosage information.

Elderly patients (aged 65 years or older) may have increased sensitivity to LORTAB ELIXIR. 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 LORTAB ELIXIR slowly in geriatric patients and follow closely for signs of central nervous system and respiratory depression [see WARNINGS].

Hydrocodone and acetaminophen 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 follow renal function.

Patients with hepatic impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose of LORTAB ELIXIR in patients with hepatic impairment and follow closely for adverse events such as respiratory depression and sedation.

Patients with renal impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose LORTAB ELIXIR in patients with renal impairment and follow closely for adverse events such as respiratory depression and sedation.

LORTAB ELIXIR contains hydrocodone, a Schedule II controlled substance.

LORTAB ELIXIR contains hydrocodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol, can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS].

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

LORTAB ELIXIR, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Do not abruptly discontinue LORTAB ELIXIR in a patient physically dependent on opioids. Rapid tapering of LORTAB ELIXIR in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuationhas also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing LORTAB ELIXIR, gradually taper the dosage using a patient-specific plan that considers the following: the dose of LORTAB ELIXIR the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION, WARNINGS].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS; Pregnancy].

Acute overdosage with LORTAB ELIXIR 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, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Ensure accuracy when prescribing, dispensing, and administering LORTAB ELIXIR to avoid dosing errors due to confusion between mg and mL, and with other hydrocodone bitartrate and acetaminophen oral solutions of different concentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume.

Always use a calibrated measuring devise when administering LORTAB ELIXIR to ensure the dose is measured and administered accurately. Health care providers should recommend a dropper that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS].

Initiate the dosing regimen for each patient individually; taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS].

Follow patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with LORTAB ELIXIR and adjust the dosage accordingly [see WARNINGS].

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with LORTAB ELIXIR [see WARNINGS; Life-Threatening Respiratory Depression, PRECAUTIONS; Information for Patients/Caregivers].

Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing regulations (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).

Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see WARNINGS; Addiction, Abuse, and Misuse, Life-Threatening Respiratory Depression, Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants].

Consider prescribing naloxone when the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.

Individually titrate LORTAB ELIXIR to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving LORTAB ELIXIR to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see WARNINGS]. 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 LORTAB ELIXIR dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Do not abruptly discontinue LORTAB ELIXIR 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 LORTAB ELIXIR, there are a variety of factors that should be considered, including the dose of LORTAB ELIXIR 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 LORTAB ELIXIR 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 2 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, monitor 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 a long duration 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 [see WARNINGS; Withdrawal, DRUG ABUSE AND DEPENDENCE].