Drug Safety-related Labeling Changes (SrLC)

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XANAX XR (NDA-021434)

(ALPRAZOLAM)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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01/13/2023 (SUPPL-22)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.8 Neonatal Sedation and Withdrawal Syndrome

Newly added subsection:

Use of XANAX XR late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate [see Use in Specific Populations (8.1)]. Monitor neonates exposed to XANAX XR during pregnancy or labor for signs of sedation and monitor neonates exposed to XANAX XR during pregnancy for signs of withdrawal; manage these neonates accordingly.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including XANAX XR, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/pregnancyregistry/.

Risk Summary

Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.8), and Clinical Considerations)].

Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data).

…

Clinical Considerations

Fetal/Neonatal adverse reactions

Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to XANAX XR during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to XANAX XR during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.8)].

…

8.2 Lactation

Additions and/or revisions underlined:

Risk Summary

Limited data from published literature reports the presence of alprazolam in human breast milk. There are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. The effects of alprazolam on lactation are unknown.

Because of the potential for serious adverse reactions, including sedation and withdrawal symptoms in breastfed infants, advise patients that breastfeeding is not recommended during treatment with XANAX XR.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Before you take XANAX XR, tell your healthcare provider about all of your medical conditions, including if you:

• have or have had depression, mood problems, or suicidal thoughts or behavior

• have liver or kidney problems

• have lung disease or breathing problems

• are pregnant or plan to become pregnant.

  • Taking XANAX XR late in pregnancy may cause your baby to have symptoms of sedation (breathing problems, sluggishness, low muscle tone), and/or withdrawal symptoms (jitteriness, irritability, restlessness, shaking, excessive crying, feeding problems).

  • Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with XANAX XR.

  • There is a pregnancy registry for women who take XANAX XR during pregnancy. The purpose of the registry is to collect information about the health of you and your baby. If you become pregnant during treatment with XANAX XR, talk to your healthcare provider about registering with the National Pregnancy Registry for Psychiatric Medications. You can register by calling 1-866-961-2388 or visiting https://womensmentalhealth.org/research/pregnancyregistry/.

• are breastfeeding or plan to breastfeed. XANAX XR passes into your breast milk.

• Talk to your healthcare provider about the best way to feed your baby if you take XANAX XR.

• Breastfeeding is not recommended during treatment with XANAX XR.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Pregnancy

Advise pregnant females that use of XANAX XR late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns [see Warnings and Precautions (5.8), Use in Specific Populations (8.1)]. Instruct patients to inform their healthcare provider if they are pregnant.

…

Lactation

Advise patients that breastfeeding is not recommended during treatment with XANAX XR [see Use in Specific Populations (8.2)].

03/01/2021 (SUPPL-18)

Approved Drug Label (PDF)

4 Contraindications

PLR conversion; additions and/or revisions underlined:

XANAX XR is contraindicated in patients:

• with known hypersensitivity to alprazolam or other benzodiazepines. Angioedema has been reported [see Adverse Reactions (6.2)].

• taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.6), Warnings and Precautions (5.5), Drug Interactions (7.1)]

5 Warnings and Precautions

PLR Conversion

5.1 Risks from Concomitant Use with Opioids

5.2 Abuse, Misuse, and Addiction

5.3 Dependence and Withdrawal Reactions

Protracted Withdrawal Syndrome

Additions and/or revisions underlined:

Certain adverse clinical events, some life-threatening, are a direct consequence of physical dependence to XANAX XR … However, in a controlled postmarketing discontinuation study of panic disorder patients who received XANAX XR, the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose …

In a controlled clinical trial in which 63 patients were randomized to XANAX XR and where withdrawal symptoms were specifically sought, the following were identified as symptoms of withdrawal: heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease, and weight loss. Other symptoms, such as anxiety and insomnia, were frequently seen during discontinuation, but it could not be determined if they were due to return of illness, rebound, or withdrawal.

5.4 Effects on Driving and Operating Machinery

Additions and/or revisions underlined:

… For the same reason, patients should be cautioned about the concomitant use of alcohol and other CNS depressant drugs during treatment with XANAX XR [see Drug Interactions (7.1)].

Newly added subsection:

5.5 Neonatal Sedation and Withdrawal Syndrome

Use of XANAX XR during later stages of pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Observe newborns for signs of sedation and neonatal withdrawal syndrome and manage accordingly [see Use in Specific Populations (8.1)].

5.6 Interaction with Drugs that Inhibit Metabolism via Cytochrome P450 3A

Additions and/or revisions underlined:

Strong CYP3A Inhibitors

XANAX XR is contraindicated in patients receiving strong inhibitors of CYP3A (such as azole antifungal agents), except ritonavir [see Contraindications (4)]. Ketoconazole and itraconazole have been shown in vivo to increase plasma alprazolam concentrations 3.98 fold and 2.70 fold, respectively.

Dosage adjustment is necessary when XANAX XR and ritonavir are initiated concomitantly or when ritonavir is added to a stable dosage of XANAX XR [see Dosage and Administration (2.6), Drug Interactions (7.1)].

Drugs demonstrated to be CYP3A inhibitors on the basis of clinical studies involving alprazolam: nefazodone and cimetidine [see Drug Interaction (7.1), Clinical Pharmacology (12.3)]. Use caution and consider dose reduction of XANAX XR, as appropriate, during co-administration with these drugs.

Additions and/or revisions underlined:

5.7 Patients with Depression

Benzodiazepines may worsen depression. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered in patients with depression.

5.8 Mania

Additions and/or revisions underlined:

Episodes of hypomania and mania have been reported in association with the use of XANAX XR in patients with depression [see Adverse Reactions (6.2)].

Additions and/or revisions underlined:

5.9 Risk in Patients with Impaired Respiratory Function

There have been reports of death in patients with severe pulmonary disease shortly after the initiation of treatment with XANAX XR. Closely monitor patients with impaired respiratory function. If signs and symptoms of respiratory depression, hypoventilation, or apnea occur, discontinue XANAX XR.

6 Adverse Reactions

PLR Conversion

Additions and/or revisions underlined:

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Risks from Concomitant Use with Opioids [see Warnings and Precautions (5.1)]

• Abuse, Misuse, and Addiction

… and on the proper use of unused drug [see Warnings and Precautions (5.2)]

• Dependence and Withdrawal Reactions

… Instruct patients that discontinuation or dosage reduction of XANAX XR may require a slow taper (see WARNINGS - Drug Abuse and Dependence and Dependence and Withdrawal Reactions [see Warnings and Precautions (5.3)]

• Effects on Driving and Operating Machinery [see Warnings and Precautions (5.4)]

• Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.5)]

• Patients with Depression [see Warnings and Precautions (5.7)]

• Risks in Patients with Impaired Respiratory Function [see Warnings and Precautions (5.9)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data in the two tables below are estimates of adverse reaction incidence among adult patients who participated in:

• 4-week placebo-controlled clinical studies with XANAX XR dosages up to 4 mg per day for the acute treatment of generalized anxiety disorder (Table 1)

• Short-term (up to 10 weeks) placebo-controlled clinical studies with XANAX XR dosages up to 10 mg per day for panic disorder, with or without agoraphobia (Table 2).

  Table 1: Adverse Reactions Occurring in greater than or equal to 1% in XANAX XR-treated Patients and Greater than Placebo-treated Patients in Placebo-Controlled Trials for Generalized Anxiety (Data in table has been rounded to the nearest percentage – please refer to label for complete information).

  In addition to the adverse reactions (i.e., greater than 1%) enumerated in the table above for patients with generalized anxiety disorder, the following adverse reactions have been reported in association with the use of benzodiazepines …

  Table 2: Adverse Reactions Occurring in greater than or equal to 1% in XANAX XR-treated Patients and Greater than Placebo- treated Patients in Placebo-Controlled Trials (Up to 10 Weeks) for Panic Disorder (Data in table has been rounded to the nearest percentage – please refer to label for complete information).

  In addition to the reactions (i.e., greater than 1%) enumerated in the table above for patients with panic disorder, the following adverse reactions have been reported …

  Adverse Reactions Reported as Reasons for Discontinuation in Treatment of Panic Disorder in Placebo-Controlled Trials

  In a larger database comprised of both controlled and uncontrolled studies in which 641 patients received XANAX XR, discontinuation-emergent symptoms which occurred at a rate of over 5% in patients treated with XANAX XR and at a greater rate than the placebo-treated group are shown in Table 3.

  Table 3: Discontinuation-Emergent Symptom Incidence Reported in greater than or equal to 5% of XANAX XR-treated Patients and greater than Placebo-treated Patients

  There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of XANAX XR [see Warning and Precautions (5.2) and Drug Abuse and Dependence (9.3)].

  6.2 Postmarketing Experience

  Additions and/or revisions underlined:

  The following adverse reactions have been identified during postapproval use of XANAX XR. Because these reactions are 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.

  Endocrine disorders: Hyperprolactinemia

  General disorders and administration site conditions: Edema peripheral

  Hepatobiliary disorders: Hepatitis, hepatic failure

  Investigations: Liver enzyme elevations

  Psychiatric disorders: Hypomania, mania

  Reproductive system and breast disorders: Gynecomastia, galactorrhea

  Skin and subcutaneous tissue disorders: Photosensitivity reaction, angioedema, Stevens-Johnson syndrome

7 Drug Interactions

PLR conversion; additions and/or revisions underlined:

7.1 Drugs Having Clinically Important Interactions with XANAX XR

Table 4 includes clinically significant drug interactions with XANAX XR [see Clinical Pharmacology (12.3)].

Table 4: Clinically Significant Drug Interactions with XANAX XR (newly created table; please refer to label for complete information.

7.2 Drug/Laboratory Test Interactions

Although interactions between benzodiazepines and commonly employed clinical laboratory tests have occasionally been reported, there is no consistent pattern for a specific drug or specific test.

8 Use in Specific Populations

PLR AND PLLR conversion; additions and revisions underlined:

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to XANAX XR during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Other Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/.

Risk Summary

Neonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and neonatal withdrawal [see Warnings and Precautions (5.4), Clinical Considerations)]. Overall available data from published observational studies of pregnant women exposed to alprazolam have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data).

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 risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Fetal/Neonatal adverse reactions

Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to benzodiazepines during pregnancy and labor for signs of sedation, respiratory depression, withdrawal, and feeding problems and manage accordingly [see Warnings and Precautions (5.4)].

Data

Human Data

Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco, and other medications, have not confirmed these findings. At this time, there is no clear evidence that alprazolam exposure in early pregnancy can cause major birth defects. Neonates exposed to benzodiazepines during the late third trimester of pregnancy or during labor have been reported to exhibit sedation and neonatal withdrawal symptoms.

8.2 Lactation

Risk Summary

Limited data from published literature reports the presence of alprazolam in human breast milk. There are reports of sedation and withdrawal symptoms in breastfed neonates and infants exposed to alprazolam. The effects of alprazolam on lactation are unknown.

Because of the potential for serious adverse reactions, including sedation and withdrawal symptoms in breastfed neonates and infants, advise patients that breastfeeding is not recommended during treatment with XANAX XR.

8.4 Pediatric Use

Safety and effectiveness of XANAX XR have not been established in pediatric patients.

8.5 Geriatric Use

XANAX XR-treated geriatric patients had higher plasma concentrations of alprazolam (due to reduced clearance) compared to younger adult patients receiving the same doses. Therefore, dosage reduction of XANAX XR is recommended in geriatric patients [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

8.6 Hepatic Impairment

Patients with alcoholic liver disease exhibit a longer elimination half-life (19.7 hours), compared to healthy subjects (11.4 hours). This may be caused by decreased clearance of alprazolam in patients with alcoholic liver disease. Dosage reduction of XANAX XR is recommended in patients with hepatic impairment [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)].

 

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

What are the possible side effects of XANAX XR?

XANAX XR may cause serious side effects, including:

PLR conversion; additions and/or revisions underlined:

The most common side effects of XANAX XR include:

• problems with coordination

• hypotension

• trouble saying words clearly (dysarthria)

• changes in sex drive (libido)

PATIENT COUNSELING INFORMATION

PLR conversion; newly created subsection. Please refer to label for complete information.

02/05/2021 (SUPPL-21)

Approved Drug Label (PDF)

Boxed Warning

(Additions and/or revisions underlined)

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE,

MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL

REACTIONS

• Concomitant use of benzodiazepines and opioids may result in profound sedation,

respiratory depression, coma, and death. Reserve concomitant prescribing of

these drugs for 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 (see WARNINGS and

PRECAUTIONS).

• The use of benzodiazepines, including XANAX, exposes users to risks of abuse,

misuse, and addiction, which can lead to overdose or death. Abuse and misuse of

benzodiazepines commonly involve concomitant use of other medications, alcohol,

and/or illicit substances, which is associated with an increased frequency of

serious adverse outcomes. Before prescribing XANAX and throughout treatment,

assess each patient’s risk for abuse, misuse, and addiction (see WARNINGS).

• The continued use of benzodiazepines, including XANAX, may lead to clinically

significant physical dependence. The risks of dependence and withdrawal

increase with longer treatment duration and higher daily dose. Abrupt

discontinuation or rapid dosage reduction of XANAX after continued use may

precipitate acute withdrawal reactions, which can be life-threatening. To reduce

the risk of withdrawal reactions, use a gradual taper to discontinue XANAX or

reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS).

5 Warnings and Precautions

Warnings

(Newly added information)

Abuse, Misuse, and Addiction

The use of benzodiazepines, including XANAX, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death (see DRUG ABUSE AND DEPENDENCE - Abuse).

Before prescribing XANAX and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of XANAX, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of XANAX along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.

Dependence and Withdrawal Reactions

To reduce the risk of withdrawal reactions, use a gradual taper to discontinue XANAX or reduce the dosage (a patient-specific plan should be used to taper the dose) (see DOSAGE AND ADMINISTRATION - Discontinuation or Dosage

Reduction of XANAX).

Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use.

Acute Withdrawal Reactions

The continued use of benzodiazepines, including XANAX, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of XANAX after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life threatening (e.g., seizures) (see DRUG ABUSE AND DEPENDENCE - Dependence).

Protracted Withdrawal Syndrome

In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE - Dependence).

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Information for Patients

(Additions and/or revisions underlined)

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

Risks from Concomitant Use with Opioids

Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when XANAX is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see PRECAUTIONS - Drug Interactions).

Abuse, Misuse, and Addiction

Inform patients that the use of XANAX, even at recommended dosages, exposes users to risks of abuse misuse and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug (see WARNINGS - Abuse, Misuse, and Addiction and DRUG ABUSE AND DEPENDENCE).

Withdrawal Reactions

Inform patients that the continued use of XANAX may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of XANAX may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of XANAX may require a slow taper (see WARNINGS - Drug Abuse and Dependence and DRUG ABUSE AND DEPENDENCE).

Inform your physician about any alcohol consumption and medicine you are taking now, including medication you may buy without a prescription. Alcohol should generally not be used during treatment with benzodiazepines.

Not recommended for use in pregnancy. Therefore, inform your physician if you are pregnant, if you are planning to have a child, or if you become pregnant while you are taking this medication. Inform your physician if you are nursing.

Until you experience how this medication affects you, do not drive a car or operate potentially dangerous machinery, etc.

Medication Guide

(Additions and/or revisions underlined)

12/16/2016 (SUPPL-16)

Approved Drug Label (PDF)

Boxed Warning

(New section added)

 

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS

 

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

 

·       Reserve concomitant prescribing of these drugs 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.

5 Warnings and Precautions

WARNINGS

(additions underlined)

 

Risks from Concomitant Use with Opioids

Concomitant use of benzodiazepines, including XANAX, and opioids may result in profound sedation, respiratory depression, coma, and death. 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 opioids alone.  If a decision is made to prescribe XANAX concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already

receiving an opioid analgesic, prescribe a lower initial dose of XANAX than indicated in the

absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking XANAX, prescribe a lower initial dose of the opioid and titrate based upon clinical response.

 

Advise both patients and caregivers about the risks of respiratory depression and sedation when XANAX is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined.

7 Drug Interactions

(additions underlined)

 

Use with Opioids

The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to

significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 Patient Counceling Information

(additions underlined)

 

1.   Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when XANAX XR is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider.

2.   Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined.

3.   Inform your physician about any alcohol consumption and medicine you are taking now, including medication you may buy without a prescription. Alcohol should generally not be used during treatment with benzodiazepines.

4.   Not recommended for use in pregnancy. Therefore, inform your physician if you are pregnant, if you are planning to have a child, or if you become pregnant while you are taking this medication.

5.   Inform your physician if you are nursing.

6.   Until you experience how this medication affects you, do not drive a car or operate potentially dangerous machinery, etc.

7.   Do not increase the dose even if you think the medication "does not work anymore" without consulting your physician. Benzodiazepines, even when used as recommended, may produce emotional and/or physical dependence.

8.   Do not stop taking this medication abruptly or decrease the dose without consulting your physician, since withdrawal symptoms can occur.

9.   Some patients may find it very difficult to discontinue treatment with XANAX XR due to severe emotional and physical dependence. Discontinuation symptoms, including

possible seizures, may occur following discontinuation from any dose, but the risk may be increased with extended use at doses greater than 4 mg/day, especially if discontinuation is too abrupt. It is important that you seek advice from your physician to discontinue treatment in a careful and safe manner. Proper discontinuation will help to decrease the possibility of withdrawal reactions that can range from mild reactions to severe reactions such as seizure.

MEDICATION GUIDE

(Newly added; please refer to label)