Category: Blog

Xanax®

• Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Xanax XR®

• Extended release tablets: 0.5 mg, 1 mg, 2 mg, 3 mg

Niravam®

• Orally disintegrating tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Alprazolam Intensol®

• Liquid (concentrate): 1 mg/ml

Generic name: alprazolam (al PRAY zoe lam)

All FDA black box warnings are at the end of this fact sheet. Please review before taking this medication.

What Is Alprazolam and What Does It Treat?

Alprazolam is a benzodiazepine. It is approved for the treatment of generalized anxiety disorder (GAD) and panic disorder with or without agoraphobia. However, benzodiazepines are also commonly used to treat difficulty sleeping and alcohol withdrawal.

Generalized Anxiety Disorder (GAD) occurs when a person experiences excessive anxiety or worry for at least six months. Other symptoms include:

• Restlessness
• Fatigue (low energy, feeling tired all the time)
• Difficulty concentrating
• Irritability
• Muscle tension
• Sleep disturbance (difficulty falling asleep or waking up in the middle of the night)

Panic Disorder occurs when a person experiences unexpected and repeated episodes of intense fear. These episodes have physical symptoms including chest pain, shortness of breath, heart palpitations, sweating, dizziness, and nausea. Fear of future episodes is also part of panic disorder.

What Is The Most Important Information I Should Know About Alprazolam?

Do not drive a car or operate machinery until you know how this medication affects you because you may notice that you feel tired or dizzy.

When starting alprazolam, anxiety or insomnia may improve rapidly or over a period of days.

Benzodiazepines, such as alprazolam, are often used for short periods of time only. They may produce emotional and/or physical dependence (addiction) even when used as recommended. Only your healthcare provider can determine the length of treatment that is right for you.

Do not stop taking alprazolam without talking to your healthcare provider first. Stopping alprazolam abruptly may result in one or more of the following withdrawal symptoms: irritability, nausea, tremor, dizziness, blood pressure changes, rapid heart rate, and seizures.

The use of alprazolam with drugs like opioid medications has led to serious side effects including slowed and difficulty breathing and death. Opioid drugs are medications used to treat pain and include medications such as: codeine, oxycodone, morphine, and illegal drugs like heroin. Some opioid medications are also in cough syrup.

If you are taking alprazolam with an opioid medication, get medical assistance immediately if you feel dizziness or sleepiness, if you have slow or troubled breathing, or if you pass out. Caregivers must get medical help right away if a patient does not respond and does not wake up.

Avoid alcohol while taking this medication.

Are There Specific Concerns About Alprazolam and Pregnancy?

If you are planning on becoming pregnant, notify your healthcare provider to best manage your medications. People living with anxiety disorders who wish to become pregnant face important decisions. It is important to discuss this with your doctor and caregivers.

Regarding breastfeeding, caution is advised since alprazolam does pass into breast milk.

What Should I Discuss With My Healthcare Provider Before Taking Alprazolam?

• Symptoms of your condition that bother you the most
• If you have thoughts of suicide or harming yourself
• Medications you have taken in the past for your condition, whether they were effective or caused any adverse effects
• If you experience side effects from your medications, discuss them with your healthcare provider. Some side effects may pass with time, but others may require changes in the medication.
• Any other psychiatric or medical problems you have including obstructive sleep apnea
• All other medications you are currently taking (including over the counter products and herbal and nutritional supplements) and any medication allergies you have
• Other non-medication treatment you are receiving such as talk therapy or substance abuse treatment. Your provider can explain how these different treatments work with the medication
• If you are elderly or are prone to falls
• If you are pregnant, plan to become pregnant, or are breast-feeding
• If you drink alcohol or use drugs

How Should I Take Alprazolam?

Alprazolam may be taken with or without food. Take with food if you experience an upset stomach.

Alprazolam may be taken every day at regular times or on an as needed (“PRN”) basis. Typically, your healthcare provider will limit the number of doses you should take in one day.

Your healthcare provider will determine the dose and method of taking the medication that is right for you based upon your response.

Alprazolam orally disintegrating tablets must remain in their original packaging. Open the package with clean dry hands before each dose. Do not try to put tablets in a pillbox if you take the orally disintegrating tablets. Take the tablets right away, do not store for later use.

Alprazolam orally disintegrating tablets will dissolve in your mouth within seconds and can be swallowed with or without liquid.

Extended release tablets: Swallow whole. Do not chew, crush or split tablet.

Alprazolam liquid: Measure with a dosing spoon or oral syringe, which you can get from your pharmacy.

If you take the medication every day (instead of ‘as needed’), use a calendar, pillbox, alarm clock, or cell phone alert to help you remember to take it. You may also ask a family member or friend to remind you or check in with you to be sure you are taking your medication.

What Happens If I Miss a Dose of Alprazolam?

If you miss a dose of alprazolam, take it as soon as you remember, unless it is closer to the time of your next dose. Discuss this with your healthcare provider. Do not double your next dose or take more than what is prescribed.

What Should I Avoid While Taking Alprazolam?

Avoid drinking alcohol and using illegal drugs while you are taking alprazolam. They may decrease the benefits (e.g., worsen your condition) and increase the adverse effects (e.g., sedation) of the medication. Alcohol increases the risk of accidental overdose with medications like alprazolam.

What Happens If I Overdose With Alprazolam?

If an overdose occurs call your doctor or 911. You may need urgent medical care. You may also contact the poison control center at 1-800-222-1222.

Symptoms of overdose include confusion, impaired coordination, slow reflexes, coma, and death.

A specific treatment to reverse the effects of alprazolam does exist. This medicine, called flumazenil, can reverse the effects of alprazolam but must be given through an IV at a hospital. Only a doctor can decide if you need this medication.

What Are The Possible Side Effects Of Alprazolam?

Common side effects

• Feeling dizzy, drowsy, fatigued, or lightheaded
• Impaired coordination, decreased ability to concentrate

If you experience these side effects after starting clonazepam they will often improve over the first week or two as you continue to take the medication

Rare/serious side effects

• Shortness of breath, trouble speaking, feeling very tired, dizziness, or passing out.
• Increased heart rate, headache, memory impairment, irritability, and restlessness may occur.
• Some people taking benzodiazepines develop a severe allergic reaction and swelling of the face. This can occur as early as with the first dose.
• Some people taking benzodiazepines for sleep have experienced various behaviors while they were asleep/not fully awake, such as sleep driving, making phone calls, and preparing or eating food. The individuals have no memory of the events when they awaken.
• Signs of feeling depressed or low mood, thoughts of harming or killing yourself, or lack of interest in life.

Are There Any Risks For Taking Alprazolam For Long Periods Of Time?

Alprazolam is a safe and effective medication when used as directed. Benzodiazepines may produce emotional and/or physical dependence (addiction) even when used as recommended. Physical dependence may develop after 2 or more weeks of daily use.

What Other Medications May Interact With Alprazolam?

The following medications may increase the levels and effects of alprazolam:

• Ketoconazole (Nizoral®), itraconazole (Sporanox®), nefazodone (Serzone®), fluvoxamine (Luvox®), and cimetidine (Tagamet®)

The following medications may decrease the levels and effects of alprazolam:

• Carbamazepine (Tegretol®), phenytoin (Dilantin®), and phenobarbital (Luminal®)

Alprazolam should not be taken with other benzodiazepine medications.

Alprazolam may cause drowsiness, so caution should be used when combining it with other medications that cause drowsiness. These could include:

• Antihistamines such as diphenhydramine (Benadryl®)
• Narcotic pain medication such as morphine, oxycodone (OxyContin®), and hydrocodone (Vicodin® and Lortab®)
• Opioid cough medications such as codeine cough syrup
• Sleeping medications such as zolpidem (Ambien®)
• Other anti-anxiety medications, antipsychotic medications, certain anticonvulsant medications, and tricyclic antidepressant medications (such as amitriptyline)

How Long Does It Take For Alprazolam To Work?

When starting alprazolam, anxiety or insomnia may improve rapidly or over a period of days or within hours of the first dose of medication.

Summary of Black Box Warnings

The FDA has found that benzodiazepine drugs, such as alprazolam, when used in combination with opioid medications or other sedating medications can result in serious adverse reactions including slowed or difficult breathing and death. Patients taking opioids with benzodiazepines, other sedating medications, or alcohol, and caregivers of these patients, should seek immediate medical attention if that start to experience unusual dizziness or lightheadedness, extreme sleepiness, slow or difficulty breathing, or unresponsiveness.

Phentermine stimulates the release of norepinephrine, and to a lesser extent serotonin (5-HT, 5-hydroxytryptamine) and dopamine, from nerve terminals. Only one RCT, published in 1968, evaluated the effect of at least 8 months of phentermine therapy on body weight.³³⁴ In that study, 108 obese women were randomized to receive an LCD and treatment with either daily phentermine (30 mg/day), daily phentermine every other month alternating with daily placebo every other month, or daily placebo for 36 weeks. Of the 64 subjects who completed the study, those randomized to either continuous or every-other-month phentermine therapy achieved the same 13% weight loss, which was greater than the 5% weight loss observed in the placebo group. In a more recent trial, subjects who completed 28 weeks of therapy with one half (15 mg/day) or one fourth (7.5 mg/day) the usual dose of phentermine had a 7.4% and 6.7% weight loss, respectively, compared with 2.3% weight loss in the placebo group.³³⁵ The most common side effects of phentermine are dry mouth, insomnia, and constipation. Although all sympathomimetic agents can increase blood pressure and heart rate, these abnormalities usually do not occur with phentermine therapy in the presence of weight loss.

Usual Adult Dose for Chronic Pain

Extended-Release (ER):
18 years or older (tramadol-naive): 100 mg orally once a day
-Individually titrate in 100 mg increments every 5 days to an effective dose that minimizes adverse reactions
-Maximum Dose: 300 mg/day

For patients CURRENTLY receiving Immediate-Release (IR) Tramadol:
Initial Dose: Calculate 24-hour IR requirement and initiate with a total daily ER dose rounded down to the next lowest 100 mg increment orally once a day

Conversion from OTHER Opioids: Discontinue all other around the clock opioid drugs prior to initiating therapy
-Initial dose: 100 mg ER orally once a day
-Individually titrate in 100 mg increments every 5 days to an effective dose that minimizes adverse reactions
-Maximum Dose: 300 mg/day

Comments:
-Due to limitations of dose selection with ER formulations, some patients may not be able to convert from the IR to ER.
-The ER products should not be used with other tramadol products and should not be taken more often than once a day.
-Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of therapy and following dose increases.
-For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, tolerability can be improved by initiating slowly, possibly with the immediate-release product.
-This drug is not recommended for patients less than 18 years old.

Use: For the management of pain severe enough to require around-the-clock long-term opioid treatment for which alternative treatment options are inadequate.

Usual Geriatric Dose for Pain

Dose selection should be cautious generally starting at the low end of the dose range

Over 75 years:
Maximum dose of Immediate-release: 300 mg per day

Comments:
-Respiratory depression is the chief risk for elderly patients treated with opioids; titrate dose slowly and monitor closely for signs of central nervous system and respiratory depression.
-Because this drug is substantially excreted by the kidney, consider monitoring renal function.

Usual Geriatric Dose for Chronic Pain

Dose selection should be cautious generally starting at the low end of the dose range

Over 75 years:
Maximum dose of Immediate-release: 300 mg per day

Comments:
-Respiratory depression is the chief risk for elderly patients treated with opioids; titrate dose slowly and monitor closely for signs of central nervous system and respiratory depression.
-Because this drug is substantially excreted by the kidney, consider monitoring renal function.

Usual Pediatric Dose for Pain

Tramadol is not recommended for use in pediatric patients

17 years or older: See Adult Dose

Renal Dose Adjustments

Immediate-release:
-CrCl less than 30 mL/min: Increase dosing interval to every 12 hours; Maximum dose should not exceed 200 mg per day

Extended-release:
-CrCl less than 30 mL/min: Use is not recommended

Liver Dose Adjustments

Immediate-release:
-Patients with cirrhosis: 50 mg orally every 12 hours

Extended-release:
-Severe hepatic impairment (Child-Pugh Class C): Use is not recommended

Dose Adjustments

Concomitant use of Drugs affecting CYP450 Isoenzymes:
-CYP450 3A4 inhibitors/inducers and CYP450 2D6 inhibitors: Interactions are complex, consult drug interaction monographs

For patients who have received this drug for an extended-period:
-Gradually decrease dose by 25% to 50% every 2 to 4 days
-If patient develops signs or symptoms of withdrawal, raise the dose to the previous level and taper more slowly by either increasing the interval between decreases, decreasing the amount of change in dose, or both.
-Do not abruptly discontinue therapy, especially for patients receiving extended-release product.

Precautions

US BOXED WARNINGS: ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF TRAMADOL AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYP450 ISOENZYMES; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:
-Addiction, Abuse, and Misuse: Use of this drug exposes patients and other users to the risks of opioid addiction and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
-Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required 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 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. Monitor for respiratory depression, especially during initiation or following a dose increase.
-Accidental Ingestion of/exposure to even one dose, especially by children, can result in a fatal overdose.
-Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases occurred following tonsillectomy and/or adenoidectomy, and in at least 1 case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP450 2D6 polymorphism. This drug is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid use in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.
-Neonatal Opioid Withdrawal Syndrome may result from prolonged maternal opioid use during pregnancy; it may be life-threatening if not recognized and treated; management according to protocols developed by neonatology experts will be required. If opioid use is needed for a prolonged period in a pregnant woman, she should be advised of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment be available.
-Concomitant use or discontinuation of CYP450 isoenzymes including CYP450 3A4 inducers, CYP450 3A4 inhibitors, or CYP450 2D6 inhibitors are complex; concomitant use requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.
-Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

CONTRAINDICATIONS:
-Children less than 12 years of age
-Postoperative pain management in pediatric patients undergoing tonsillectomy and/or adenoidectomy
-Hypersensitivity (e.g., anaphylaxis) to the active substance
-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
-Concomitant use or within 2 weeks of monoamine oxidase inhibitors (MAOIs)

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule IV

Dialysis

Hemodialysis patients can receive their regular dose on dialysis days since only 7% of dose is removed
Peritoneal dialysis: No data available