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Alprazolam (Alprazolam) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The information included in the subsection on Adverse Events Observed in Short-Term, Placebo-Controlled Trials with alprazolam extended-release tablets is based on pooled data of five 6- and 8-week placebo-controlled clinical studies in panic disorder.

Adverse event reports were elicited either by general inquiry or by checklist, and were recorded by clinical investigators using terminology of their own choosing. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened during therapy following baseline evaluation. In the tables and tabulations that follow, standard MedDRA terminology (version 4.0) was used to classify reported adverse events.

Adverse Events Observed in Short-Term, Placebo-Controlled Trials of Alprazolam Extended-Release

Adverse Events Reported as Reasons for Discontinuation of Treatment in Placebo-Controlled Trials

Approximately 17% of the 531 patients who received alprazolam extended-release in placebo-controlled clinical trials for panic disorder had at least one adverse event that led to discontinuation compared to 8% of 349 placebo-treated patients. The most common events leading to discontinuation and considered to be drug-related (ie, leading to discontinuation in at least 1% of the patients treated with alprazolam extended-release at a rate at least twice that of placebo) are shown in the following table.

Common Adverse Events Leading to Discontinuation of Treatment in Placebo-Controlled Trials
 System Organ Class/Adverse Event  Percentage of Patients Discontinuing
Due to Adverse Events
   Alprazolam
Extended-Release
(n=531)
 Placebo
(n=349)
 Nervous system disorders    
    Sedation  7.5  0.6
    Somnolence  3.2  0.3
    Dysarthria  2.1  0
    Coordination abnormal  1.9  0.3
    Memory impairment  1.5  0.3
 General disorders/administration site conditions    
    Fatigue  1.7  0.6
 Psychiatric disorders    
    Depression  2.5  1.2

Adverse Events Occurring at an Incidence of 1% or More Among Patients Treated with Alprazolam Extended-Release

The prescriber should be aware that adverse event incidence cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with event incidence obtained from other clinical investigations involving different treatments, uses, and investigators. The cited values, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.

The following table shows the incidence of treatment-emergent adverse events that occurred during 6- to 8-week placebo-controlled trials in 1% or more of patients treated with alprazolam extended-release where the incidence in patients treated with alprazolam extended-release was greater than the incidence in placebo-treated patients. The most commonly observed adverse events in panic disorder patients treated with alprazolam extended-release (incidence of 5% or greater and at least twice the incidence in placebo patients) were: sedation, somnolence, memory impairment, dysarthria, coordination abnormal, ataxia, libido decreased (see table).

Treatment-Emergent Adverse Events: Incidence in Short-Term, Placebo-Controlled Clinical Trials with Alprazolam Extended-Release
 System Organ Class/Adverse Event  Percentage of Patients
Reporting Adverse
Event
 Alprazolam
Extended-Release
(n=531)
 Placebo
(n=349)
 Nervous system disorders    
    Sedation  45.2  22.6
    Somnolence  23.0  6.0
    Memory impairment  15.4  6.9
    Dysarthria  10.9  2.6
    Coordination abnormal  9.4  0.9
    Mental impairment  7.2  5.7
    Ataxia  7.2  3.2
    Disturbance in attention  3.2  0.6
    Balance impaired  3.2  0.6
    Paresthesia  2.4  1.7
    Dyskinesia  1.7  1.4
    Hypoesthesia  1.3  0.3
    Hypersomnia  1.3  0
 General disorders/administration site conditions    
    Fatigue  13.9  9.2
    Lethargy  1.7  0.6
 Infections and infestations    
    Influenza  2.4  2.3
    Upper respiratory tract infections  1.9  1.7
 Psychiatric disorders    
    Depression  12.1  9.2
    Libido decreased  6.0  2.3
    Disorientation  1.5  0
    Confusion  1.5  0.9
    Depressed mood  1.3  0.3
    Anxiety  1.1  0.6
 Metabolism and nutrition disorders    
    Appetite decreased  7.3  7.2
    Appetite increased  7.0  6.0
    Anorexia  1.5  0
 Gastrointestinal disorders    
    Dry mouth  10.2  9.7
    Constipation  8.1  4.3
    Nausea  6.0  3.2
    Pharyngolaryngeal pain  3.2  2.6
 Investigations    
    Weight increased  5.1  4.3
    Weight decreased  4.3  3.7
 Injury, poisoning, and procedural complications    
    Road traffic accident  1.5  0
 Reproductive system and breast disorders    
    Dysmenorrhea  3.6  2.9
    Sexual dysfunction  2.4  1.1
    Premenstrual syndrome  1.7  0.6
 Musculoskeletal and connective tissue disorders    
    Arthralgia  2.4  0.6
    Myalgia  1.5  1.1
    Pain in limb  1.1  0.3
 Vascular disorders    
    Hot flushes  1.5  1.4
 Respiratory, thoracic, and mediastinal disorders    
    Dyspnea  1.5  0.3
    Rhinitis allergic  1.1  0.6
 Skin and subcutaneous tissue disorders    
    Pruritis  1.1  0.9

Other Adverse Events Observed During the Premarketing Evaulation of Alprazolam Extended-Release Tablets

Following a list of MedDRA terms that reflect treatment-emergent adverse events reported by 531 patients with panic disorder treated with alprazolam extended-release. All potentially important reported events are included except those already listed in the above table or elsewhere in labeling, those events for which a drug cause was remote, those event terms that were so general as to be uninformative, and those events that occurred at rates similar to background rates in the general population. It is important to emphasize that, although the events reported occurred during treatment with alprazolam extended-release, they were not necessarily caused by the drug. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on 1 or more occasions in at least 1/l00 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

Cardiac disorders:     Frequent: palpitation; Infrequent: sinus tachycardia
Ear and Labyrinth disorders:     Frequent: Vertigo; Infrequent: tinnitus, ear pain
Eye disorders:     Frequent: blurred vision; Infrequent: mydriasis, photophobia
Gastrointestinal disorders:     Frequent: diarrhea, vomiting, dyspepsia, abdominal pain; Infrequent: dysphagia, salivary hypersecretion
General disorders and administration site conditions:     Frequent: malaise, weakness, chest pains; Infrequent: fall, pyrexia, thirst, feeling hot and cold, edema, feeling jittery, sluggishness, asthenia, feeling drunk, chest tightness, increased energy, feeling of relaxation, hangover, loss of control of legs, rigors
Musculoskeletal and connective tissue disorders:     Frequent: back pain, muscle cramps, muscle twitching
Nervous system disorders:     Frequent: headache, dizziness, tremor; Infrequent: amnesia, clumsiness, syncope, hypotonia, seizures, depressed level of consciousness, sleep apnea syndrome, sleep talking, stupor
Psychiatric system disorders:     Frequent: irritability, insomnia, nervousness, derealization, libido increased, restlessness, agitation, depersonalization, nightmare; Infrequent: abnormal dreams, apathy, aggression, anger, bradyphrenia, euphoric mood, logorrhea, mood swings, dysphonia, hallucination, homicidal ideation, mania, hypomania, impulse control, psychomotor retardation, suicidal ideation
Renal and urinary disorders:     Frequent: difficulty in micturition; Infrequent: urinary frequency, urinary incontinence
Respiratory, thoracic, and mediastinal disorders:     Frequent: nasal congestion, hyperventilation; Infrequent: choking sensation, epistaxis, rhinorrhea
Skin and subcutaneous tissue disorders:     Frequent: sweating increased; Infrequent: clamminess, rash, urticaria
Vascular disorders:     Infrequent: hypotension

The categories of adverse events reported in the clinical development program for alprazoalam tablets in the treatment of panic disorder differ somewhat from those reported for alprazolam extended-release tablets because the clinical trials with alprazolam tablets and alprazolam extended-release tablets used different standard medical nomenclature for reporting the adverse events. Nevertheless, the types of adverse events reported in the clinical trials with alprazolam tablets were generally the same as those reported in the clinical trials with alprazolam extended-release.

Discontinuation-Emergent Adverse Events Occurring at an incidence of 5% or More Among Patients Treated with Alprazolam Extended-Release

The following table shows the incidence of discontinuation-emergent adverse events that occurred during short-term, placebo-controlled trials in 5% or more of patients treated with alprazolam extended-release where the incidence in patients treated with alprazolam extended-release was two times greater than the incidence in placebo-treated patients.

Discontinuation-Emergent Symptoms: Incidence in Short-Term, Placebo-Controlled Trials with Alprazolam Extended-Release
 System Organ Class/Adverse Event  Percentage of Patients Reporting
Adverse Event
 Alprazolam
Extended-Release
(n=422)
 Placebo
(n=261)
 Nervous system disorders    
    Tremor  28.2  10.7
    Headache  26.5  12.6
    Hypoesthesia  7.8  2.3
    Paresthesia  7.1  2.7
 Psychiatric disorders    
    Insomnia  24.2  9.6
    Nervousness  21.8  8.8
    Depression  10.9  5.0
    Derealization  8.0  3.8
    Anxiety  7.8  2.7
    Depersonalization  5.7  1.9
 Gastrointestinal disorders    
    Diarrhea  12.1  3.1
 Respiratory, thoracic and mediastinal
disorders
   
    Hyperventilation  8.5  2.7
 Metabolism and nutrition disorders    
    Appetite decreased  9.5  3.8
 Musculoskeletal and connective tissue
disorders
   
    Muscle twitching  7.4  2.7
 Vascular disorders    
    Hot flushes  5.9  2.7

There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam (see WARNINGS).

To discontinue treatment in patients taking alprazolam extended-release tablets, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam extended-release tablets be decreased by no more than 0.5 mg every three days (see DOSAGE AND ADMINISTRATION). Some patients may benefit from an even slower dosage reduction. In a controlled postmarketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome.

As with all benzodiazepines, paradoxical reactions such as stimulation, increased muscle spasticity, sleep disturbances, hallucinations, and other adverse behavioral effects such as agitation, rage, irritability, and aggressive or hostile behavior have been reported rarely. In many of the spontaneous case reports of adverse behavioral effects, patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Should any of the above events occur, alprazolam should be discontinued. Isolated published reports involving small numbers of patients have suggested that patients who have borderline personality disorder, a prior history of violent or aggressive behavior, or alcohol or substance abuse may be at risk for such events. Instances of irritability, hostility, and intrusive thoughts have been reported during discontinuation of alprazolam in patients with posttraumatic stress disorder.

Post Introduction Reports

Various adverse drug reactions have been reported in association with the use of alprazolam tablets since market introduction. The majority of these reactions were reported through the medical event voluntary reporting system. Because of the spontaneous nature of the reporting of medical events and the lack of controls, a causal relationship to the use of alprazolam tablets cannot be readily determined. Reported events include:gastrointestinal disorder; hypomania, mania, liver enzyme elevations, hepatitis, hepatic failure, Stevens-Johnson syndrome, angioedema, peripheraledema, hyperprolactinemia, gynecomastia, and galactorrhea (see PRECAUTIONS).



REPORTS OF SUSPECTED ALPRAZOLAM SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Alprazolam. The information is not vetted and should not be considered as verified clinical evidence.

Possible Alprazolam side effects / adverse reactions in 53 year old male

Reported by a consumer/non-health professional from Costa Rica on 2011-10-04

Patient: 53 year old male

Reactions: Mood Altered, Fear, Mental Disorder, Anger, Boredom, Asthenia, Tremor

Suspect drug(s):
Alprazolam
    Indication: Nightmare

Alprazolam
    Dosage: 1 mg, unk
    Administration route: Oral
    Indication: Hiatus Hernia
    Start date: 2010-01-01
    End date: 2011-01-01

Alprazolam
    Dosage: 2 mg, daily
    Administration route: Oral
    Indication: Migraine
    Start date: 2011-06-01



Possible Alprazolam side effects / adverse reactions in 70 year old male

Reported by a physician from France on 2011-10-04

Patient: 70 year old male

Reactions: Bronchospasm, Drug Rash With Eosinophilia and Systemic Symptoms

Adverse event resulted in: hospitalization

Suspect drug(s):
Bumetanide
    Dosage: ;iv
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-10-30
    End date: 2010-11-03

Eupressyl (Urapidil)
    Dosage: ;iv
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-10-14
    End date: 2010-11-21

Claventin (Claventin /00973701/)
    Dosage: 10 gm; ;iv
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-10-29
    End date: 2010-11-12

Doribax
    Dosage: 1 gm;qd;po
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-11-15
    End date: 2010-11-26

Orgaran
    Dosage: ; sc
    Start date: 2010-10-25
    End date: 2011-01-26

Alprazolam
    Dosage: 0.25 mg; qd;po
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-11-15
    End date: 2010-12-06

Bactrim
    Dosage: 400 mg; ;iv
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-10-29
    End date: 2010-11-06

Aldomet
    Dosage: ;po
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-11-15
    End date: 2011-01-10

Furosemide
    Dosage: ;po
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-10-14
    End date: 2011-01-17



Possible Alprazolam side effects / adverse reactions in 46 year old female

Reported by a consumer/non-health professional from Germany on 2011-10-06

Patient: 46 year old female

Reactions: Extrasystoles, Ventricular Tachycardia

Suspect drug(s):
Alprazolam



See index of all Alprazolam side effect reports >>

Drug label data at the top of this Page last updated: 2012-02-13

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