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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
HYDROCODONE BITARTRATE AND GUAIFENESIN (NDA-208085)
(GUAIFENESIN; HYDROCODONE BITARTRATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/31/2018 (SUPPL-1)
4 Contraindications
4 CONTRAINDICATIONS(Additions and/or revisions are underlined)
Xtrelus is contraindicated for:
All children younger than 6 years of age
Xtrelus is also contraindicated in patients with:
Significant respiratory depression.
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.
Known or suspected gastrointestinal obstruction, including paralytic ileus.
Hypersensitivity to hydrocodone, guaifenesin, or any of the inactive ingredients in Xtrelus.
5 Warnings and Precautions
5.1 Addiction, Abuse, and Misuse(Additions and/or revisions are underlined)
Xtrelus contains hydrocodone, a Schedule II controlled substance. As an opioid, Xtrelus exposes users to the risks of addiction, abuse, and, which can lead to overdose and death. Reserve Xtrelus for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Assess each patient’s risk prior to prescribing Xtrelus, prescribe Xtrelus for the shortest duration that is consistent with individual patient treatment goals, monitor all patients regularly for the development of addiction or abuse, and refill only after reevaluation of the need for continued treatment.
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Xtrelus. Addiction can occur at recommended dosages and if the drug is misused or abused. 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). Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Xtrelus.
…
(Additions and/or revisions are underlined)
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, including hydrocodone, one of the active ingredients in Xtrelus. Hydrocodone produces dose-related respiratory depression by directly acting on the brain stem respiratory center that controls respiratory rhythm and may produce irregular and periodic breathing. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression includes discontinuation of Xtrelus, close observation, supportive measures, and use of opioid antagonists (e.g. naloxone), depending on the patient’s clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Xtrelus, the risk is greatest during the initiation of therapy, when Xtrelus is used concomitantly with other drugs that may cause respiratory depression, in patients with chronic pulmonary disease or decreased respiratory reserve, and in patients with altered pharmacokinetics or altered clearance (e.g. elderly, cachectic, or debilitated patients).
To reduce the risk of respiratory depression, proper dosing of Xtrelus is essential. Monitor patients closely, especially within the first 24- 72 hours of initiating therapy or when used in patients at higher risk.
Overdose of hydrocodone in adults has been associated with fatal respiratory depression, and the use of hydrocodone in children younger than 6 years of age has been associated with fatal respiratory depression when used as recommended. Accidental ingestion of even one dose of Xtrelus, especially by children, can result in respiratory depression and death.
5.3 Risks with Use in Pediatric Populations
(Additions and/or revisions are underlined)
Children are particularly sensitive to the respiratory depressant effects of hydrocodone. Because of the risk of life-threatening respiratory depression and death, Xtrelus is contraindicated in children less than 6 years of age.
Use of Xtrelus in children also exposes them to the risks of addiction, abuse, and misuse , which can lead to overdose and death. Because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks of use of hydrocodone in pediatric patients, Xtrelus is not indicated for use in patients younger than 18 years of age.
5.4 Risks with Use in Other At-Risk Populations
(Additions and/or revisions are underlined)
Unresponsive Cough
The dosage of Xtrelus should not be increased if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease.
Asthma and Other Pulmonary Disease
The use of Xtrelus in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.Opioid analgesics and antitussives, including hydrocodone, one of the active ingredients in Xtrelus, should not be used in patients with acute febrile illness associated with productive cough or in patients with chronic respiratory disease where interference with ability to clear the tracheobronchial tree of secretions would have a deleterious effect on the patient’s respiratory function.
Xtrelus-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Xtrelus.
Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
Because of the risk of respiratory depression, avoid the use of opioid antitussives, including Xtrelus in patients with compromised respiratory function, patients at risk of respiratory failure, and in elderly, cachectic, or debilitated patients. If Xtrelus is prescribed, monitor such patients closely, particularly when initiating Xtrelus and when Xtrelus is given concomitantly with other drugs that depress respiration.
5.5 Risk of Accidental Overdose and Death due to Medication Errors
(Additions and/or revisions are underlined)
Dosing errors can result in accidental overdose and death. To reduce the risk of overdose and respiratory depression, ensure that the dose of Xtrelus is communicated clearly and dispensed accurately.
Activities Requiring Mental Alertness: Risks of Driving and Operating Machinery
(Additions and/or revisions are underlined)
Hydrocodone, one of the active ingredients in Xtrelus, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of Xtrelus. Avoid concurrent use of Xtrelus with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur.
Risks from Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers
(Additions and/or revisions are underlined)
Concomitant use of Xtrelus 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, which may cause potentially fatal respiratory, particularly when an inhibitor is added after a stable dose of Xtrelus is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Xtrelus-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions.
Concomitant use of Xtrelus 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 hydrocodone.
Avoid the use of Xtrelus in patients who are taking a CYP3A4 inhibitor or inducer. If concomitant use of Xtrelus with a CYP3A4 inhibitor or inducer is necessary, monitor patients for signs and symptoms that may reflect opioid toxicity and opioid withdrawal.
5.8 Risks from Concomitant Use with Benzodiazepines or other CNS Depressants
(Additions and/or revisions are underlined)
Concomitant use of opioids, including Xtrelus, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.
Advise both patients and caregivers about the risks of respiratory depression and sedation if Xtrelus is used with benzodiazepines, alcohol, or other CNS depressants.
Patients must not consume alcoholic beverages, or prescription or non-prescription products containing alcohol, while on Xtrelus therapy. The co-ingestion of alcohol with Xtrelus may result in increased plasma levels and a potentially fatal overdose of hydrocodone.
5.9 Risks of Use in Patients with Gastrointestinal Conditions
(Additions and/or revisions are underlined)
Xtrelus is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The use of hydrocodone in Xtrelus may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
The concurrent use of anticholinergics with Xtrelus may produce paralytic ileus.
The hydrocodone in Xtrelus may result in constipation or obstructive bowel disease, especially in patients with underlying intestinal motility disorders. Use with caution in patients with underlying intestinal motility disorders.
The hydrocodone in Xtrelus may cause spasm of the sphincter of Oddi, resulting in an increase in biliary tract pressure. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.
5.10 Risks of Use in Patients with Head Injury, Impaired Consciousness, Increased Intracranial Pressure, or Brain Tumors
(Additions and/or revisions are underlined)
Avoid the use of Xtrelus in patients with head injury, intracranial lesions, or a pre-existing increase in intracranial pressure. In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), Xtrelus may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Furthermore, opioids produce adverse reactions that may obscure the clinical course of patients with head injuries.
5.11 Increased Risk of Seizures in Patients with Seizure Disorders
(Additions and/or revisions are underlined)
The hydrocodone in Xtrelus 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. Monitor patients with a history of seizure disorders for worsened seizure control during Xtrelus therapy.
5.12 Severe Hypotension
(Additions and/or revisions are underlined)
Xtrelus 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). Monitor these patients for signs of hypotension after initiating Xtrelus.
In patients with circulatory shock, Xtrelus may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Xtrelus in patients with circulatory shock.
5.13 Neonatal Opioid Withdrawal Syndrome
(Additions and/or revisions are underlined)
Xtrelus is not recommended for use in pregnant women. Prolonged use of Xtrelus 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.
5.15 Drug/Laboratory Test Interactions
(Additions and/or revisions are underlined)
Because opioid agonists may increase biliary tract pressure, with resultant increase in plasma amylase or lipase levels, determination of these enzyme levels may be unreliable for 24 hours after administration of a dose of Xtrelus.
6 Adverse Reactions
6 ADVERSE REACTIONS(Additions and/or revisions are underlined)
…
The following adverse reactions have been identified during clinical studies, in the literature, or during post- approval use of hydrocodone and/or guaifenesin. Because these reactions may be reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The most common adverse reactions to Xtrelus include: Sedation (somnolence, mental clouding, lethargy), impaired mental and physical performance, lightheadedness, dizziness, headache, dry mouth, nausea, vomiting, and constipation.
Other reactions include:
anaphylaxis: Anaphylaxis has been reported with hydrocodone, one of the ingredients in Xtrelus. …
7 Drug Interactions
7 DRUG INTERACTIONS(Additions and/or revisions are underlined)
No specific drug interaction studies have been conducted with Xtrelus.
7.1 Alcohol
(Additions and/or revisions are underlined)
Concomitant use of alcohol with Xtrelus can result in an increase of hydrocodone plasma levels and potentially fatal overdose of hydrocodone. Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products containing alcohol while on Xtrelus therapy.
7.2 Inhibitors of CYP3A4 and CYP2D6
(Additions and/or revisions are underlined)
The concomitant use of Xtrelus and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), or protease inhibitors (e.g., ritonavir), can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of Xtrelus and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of Xtrelus is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone.
Avoid the use of Xtrelus while taking a CYP3A4 or CYP2D6 inhibitor. If concomitant use is necessary, monitor patients for respiratory depression and sedation at frequent intervals.
7.3 CYP3A4 Inducers
(Additions and/or revisions are underlined)
The concomitant use of Xtrelus and CYP3A4 inducers such as rifampin, carbamazepine, or phenytoin, can decrease the plasma concentration of hydrocodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase, which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.
Avoid the use of Xtrelus in patients who are taking CYP3A4 inducers. If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy.
7.4 Benzodiazepines, and Other CNS Depressants
(Additions and/or revisions are underlined)
Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Avoid the use of Xtrelus in patients who are taking benzodiazepines or other CNS depressants, and instruct patients to avoid consumption of alcohol while on Xtrelus.
7.5 Serotonergic Drugs
(Additions and/or revisions are underlined)
The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation. Discontinue Xtrelus if serotonin syndrome is suspected.
7.6 Monoamine Oxidase Inhibitors (MAOIs)
(Additions and/or revisions are underlined)
Avoid the use of Xtrelus in patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 14 days. The use of MAOIs or tricyclic antidepressants with hydrocodone, one of the active ingredients in Xtrelus, may increase the effect of either the antidepressant or hydrocodone. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
7.7 Muscle Relaxants
(Additions and/or revisions are underlined)
Hydrocodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Avoid the use of Xtrelus in patients taking muscle relaxants. If concomitant use is necessary, monitor patients for signs of respiratory depression that may be greater than otherwise expected.
7.9 Anticholinergic Drugs
(Additions and/or revisions are underlined)
The concomitant use of anticholinergic drugs with Xtrelus may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when Xtrelus is used concomitantly with anticholinergic drugs.
8 Use in Specific Populations
8.1 Pregnancy(Additions and/or revisions are underlined)
Risk Summary
Xtrelus is not recommended for use in pregnant women, including during or immediately prior to labor.
Prolonged use of opioids during pregnancy may cause neonatal opioid withdrawal syndrome.
There are no available data with Xtrelus use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. Published studies with hydrocodone have reported inconsistent findings and have important methodological limitations.
Reproductive toxicity studies have not been conducted with Xtrelus; however, studies are available with individual active ingredients or related active ingredients.
…
Labor or Delivery
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. Opioids, including Xtrelus, 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 dilatation, which tends to shorten labor. Monitor neonates exposed to opioids during labor for signs of excess sedation and respiratory depression.
Human Data
Hydrocodone
A limited number of pregnancies have been reported in published observational studies and postmarketing reports describing hydrocodone use during pregnancy. However, these data cannot definitely establish or exclude any drug-associated risk during pregnancy. Methodological limitations of these observational studies include small sample size and lack of details regarding dose, duration and timing of exposure.
Animal Data
Reproductive toxicity studies have not been conducted with Xtrelus; however, studies are available with individual active ingredients or related active ingredients.
8.2 Lactation
(Additions and/or revisions are underlined)
Risk Summary
Because of the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Xtrelus.
There are no data on the presence of Xtrelus in human milk, the effects of Xtrelus on the breastfed infant, or the effects of Xtrelus on milk production; however, data are available with hydrocodone.
…
Clinical Considerations
Infants exposed to Xtrelus 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 is stopped, or when breastfeeding is stopped.
8.3 Females and Males of Reproductive Potential
(Additions and/or revisions are underlined)
Infertility
Chronic use of opioids, such as hydrocodone, a component of Xtrelus, may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.
8.4 Pediatric Use
(Additions and/or revisions are underlined)
TRADENAMETRADENAME is not indicated for use in patients younger than 18 years of age because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks for use of hydrocodone in these patients.
Life-threatening respiratory depression and death have occurred in children who received hydrocodone. Because of the risk of life-threatening respiratory depression and death, Xtrelus is contraindicated in children less than 6 years of age.
8.5 Geriatric Use
(Additions and/or revisions are underlined)
Clinical studies have not been conducted with Xtrelus in geriatric populations.
Use caution when considering the use of Xtrelus in patients 65 years of age or older. Elderly patients may have increased sensitivity to hydrocodone; greater frequency of decreased hepatic, renal, or cardiac function; or concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, including Xtrelus. Respiratory depression has occurred after large initial doses of opioids were administered to patients who were not opioid- tolerant or when opioids were co-administered with other agents that depress respiration.
Hydrocodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, monitor these patients closely for respiratory depression, sedation, and hypotension.
8.6 Renal Impairment
(Additions and/or revisions are underlined)
The pharmacokinetics of Xtrelus has not been characterized in patients with renal impairment. Patients with renal impairment may have higher plasma concentrations than those with normal function. Xtrelus should be used with caution in patients with severe impairment of renal function, and patients should be monitored closely for signs of hydrocodone toxicity including respiratory depression, sedation, and hypotension.
8.7 Hepatic Impairment
(Additions and/or revisions are underlined)
The pharmacokinetics of Xtrelus has not been characterized in patients with hepatic impairment. Patients with severe hepatic impairment may have higher plasma concentrations than those with normal hepatic function. Therefore, Xtrelus should be used with caution in patients with severe impairment of hepatic function, and patients should be monitored closely for signs of hydrocodone toxicity including respiratory depression, sedation, and hypotension.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Addiction, Abuse, and Misuse
Inform patients that the use of Xtrelus, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death. Instruct patients not to share Xtrelus with others and to take steps to protect Xtrelus from theft or misuse.
Important Dosing and Administration Instructions
Advise patients to take Xtrelus exactly as prescribed. Advise patients not to increase the dose or dosing frequency of Xtrelus because serious adverse events such as respiratory depression may occur with overdosage.
Life-Threatening Respiratory Depression
Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Xtrelus and that it can occur even at recommended dosages. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
Accidental Ingestion
Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.2)]. Instruct patients to take steps to store Xtrelus securely and to properly dispose of unused Xtrelus in accordance with the local state guidelines and/or regulations.
Activities Requiring Mental Alertness
Advise patients to avoid engaging in hazardous tasks that require mental alertness and motor coordination such as operating machinery or driving a motor vehicle as Xtrelus may produce marked drowsiness.
Interactions with Benzodiazepines and Other Central Nervous System Depressants, Including Alcohol
Inform patients and caregivers that potentially fatal additive effects may occur if Xtrelus is used with benzodiazepines or other CNS depressants, including alcohol. Advise patients to avoid concomitant use of Xtrelus with benzodiazepines or other CNS depressants and instruct patients not to consume alcoholic beverages, as well as prescription and over-the-counter products that contain alcohol, during treatment with Xtrelus.
Advise patients of the potential for severe constipation.
Inform patients that anaphylaxis has been reported with ingredients contained in Xtrelus. Advise patients how to recognize such a reaction and when to seek medical attention.
MAOI Interaction
Inform patients not to take Xtrelus while using or within 14 days of stopping any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Xtrelus.
Inform patients that Xtrelus may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position).
Advise patients that use of Xtrelus is not recommended during pregnancy.
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that use of Xtrelus during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.
Embryo-Fetal Toxicity
Inform female patients of reproductive potential that Xtrelus can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy.
Advise women that breastfeeding is not recommended during treatment with Xtrelus.
Infertility
Inform patients that chronic use of opioids, such as hydrocodone, a component of Xtrelus, may cause reduced fertility. It is not known whether these effects on fertility are reversible.
Adrenal Insufficiency
Inform patients that Xtrelus could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms.
Serotonin Syndrome
Inform patients that Xtrelus could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications.
Disposal of Unused Xtrelus
Advise patients to properly dispose of unused Xtrelus. Advise patients to throw the drug in the household trash following these steps. 1) Remove them from their original containers and break the tablets, mix them with an undesirable substance, such as used coffee grounds or kitty litter (this makes the drug less appealing to children and pets, and unrecognizable to people who may intentionally go through the trash seeking drugs). 2) Place the mixture in a sealable bag, empty can, or other container to prevent the drug from leaking or breaking out of a garbage bag, or to dispose of in accordance with local state guidelines and/or regulations.
(Medication Guide has been added; please refer to label)