Drug Profile of ALPRAZOLAM: Faculty of Pharmacy Bahauddin Zakariya University Multan Pakistan
Drug Profile of ALPRAZOLAM: Faculty of Pharmacy Bahauddin Zakariya University Multan Pakistan
Drug Profile of ALPRAZOLAM: Faculty of Pharmacy Bahauddin Zakariya University Multan Pakistan
Submitted by
Roll NO. 55-E-16
Session: 2016-2021
Submitted T0
Dr. Abdul Majeed
Subject:
Clinical Pharmacy
FACULTY OF PHARMACY
Alprazolam is used to treat anxiety and panic disorders. It belongs to a class of medications
called benzodiazepines which act on the brain and nerves (central nervous system) to produce a
calming effect. It works by enhancing the effects of a certain natural chemical in the body
(GABA).
1.PRODUCTS DISCRIPTION:
Alprazolam is available in following brands in Pakistan.
Tablets:
0.25mg
0.5mg
1mg
2mg
2.CHEMISTRY OF ALPRAZOLAM:
Structure:
IUPAC Name: 8-chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-α] [1,4] benzodiazepine
Properties:
Physical Description: Solid
Color/Form: Crystals from ethyl acetate
Melting Point: 228-229.5 °C
Solubility:
In water, 13.1 mg/L at 25 °C (est)
Insoluble in water
Freely soluble in chloroform, soluble in alcohol; sparingly soluble in acetone; solubility
soluble in ethyl acetate
STORAGE :Store at room temperature away from light and moisture. Do not store in the
bathroom. Keep all medications away from children and pets.Do not flush medications down the
toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is
expired or no longer needed. Consult your pharmacist or local waste disposal company for more
details.
3.PHARMACOKINETICS:
3.1:Absorption
Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in
1 to 2 hours following administration. Plasma levels are proportionate to the dose given; over the dose
range of 0.5 to 3.0 mg, peak levels of 8.0 to 37 ng/mL were observed. Using a specific assay
methodology, the mean plasma elimination half-life of alprazolam has been found to be about 11.2 hours
(range: 6.3–26.9 hours) in healthy adults.
3.2:Distribution
In vitro, alprazolam is bound (80 percent) to human serum protein. Serum albumin accounts for the
majority of the binding.
3.3:Metabolism/Elimination
4.CLINICAL PHARMACOLOGY:
Alprazolam is intermediate acting benzodizepines agent with duration of action 11 to 20 hours.
4.1:MECHANISM OF ACTION:
4.2:CLINICAL USES:
Treatment of anxiety, panic attacks, and states of agitation.
Treatment of neurovegetative symptoms associated with vertigo.
Treatment of the symptoms of alcohol, opiate, and benzodiazepine withdrawal
Short-term treatment of insomnia.
Treatment of muscle spasms.
Treatment of tetanus, together with other measures of intensive treatment.
Adjunctive treatment of spastic muscular paresis (paraplegia/tetraplegia) caused by
cerebral or spinal cord conditions such as stroke, multiple sclerosis, or spinal cord injury
(long-term treatment is coupled with other rehabilitative measures)..
Palliative treatment of stiff person syndrome.
Pre- or postoperative sedation, anxiolysis or amnesia (e.g., before endoscopic or surgical
procedures).
Treatment of complications with a hallucinogen crisis and stimulant overdoses and
psychosis.
4.3: INDICATIONS:
Anxiety Disorders
XANAX Tablets (alprazolam) are indicated for the management of anxiety disorder (a condition
corresponding most closely to the APA Diagnostic and Statistical Manual [DSM-IIIR] diagnosis
of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety or
tension associated with the stress of everyday life usually does not require treatment with an
anxiolytic.
Panic Disorder
XANAX is also indicated for the treatment of panic disorder, with or without agoraphobia.
Studies supporting this claim were conducted in patients whose diagnoses corresponded closely
to the DSM-III-R/IV criteria for panic disorder .
4.4: CONTRAINDICATIONS:
Ataxia
Severe hypoventilation
Acute narrow-angle glaucoma
Severe hepatic deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor
of two)
Severe renal deficiencies (for example, patients on dialysis)
Liver disorders
Severe sleep apnea
Severe depression, particularly when accompanied by suicidal tendencies
Psychosis
Pregnancy or breast feeding
Caution required in elderly or debilitated patients
Coma or shock
Abrupt discontinuation of therapy
Acute intoxication with alcohol, narcotics, or other psychoactive substances (with the
exception of some hallucinogens or stimulants, where it is occasionally used as a
treatment for overdose)
History of alcohol or drug dependence
Myasthenia gravis, an autoimmune disorder causing marked fatiguability
Hypersensitivity or allergy to any drug in the benzodiazepine class
Alprazolam falls into category D. Alprazolam passes to the baby and may cause harm to
the unborn baby. In addition, the baby may be born with respiratory and other problems if
the mother uses alprazolam while pregnant. However, this medication may sometimes still
help human mothers and their babies more than it might cause harm.
5. DOSAGE SCHEDULE:
Dosage should be individualized for maximum beneficial effect. While the usual daily dosages
given below will meet the needs of most patients, there will be some who require doses greater
than 4 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects.
Treatment for patients with anxiety should be initiated with a dose of 0.25 to 0.5 mg given three
times daily. The dose may be increased to achieve a maximum therapeutic effect, at intervals of
3 to 4 days, to a maximum daily dose of 4 mg, given in divided doses. The lowest possible
effective dose should be employed and the need for continued treatment reassessed frequently.
The risk of dependence may increase with dose and duration of treatment.
5.2:Panic Disorder
The successful treatment of many panic disorder patients has required the use of XANAX at
doses greater than 4 mg daily. In controlled trials conducted to establish the efficacy of XANAX
in panic disorder, doses in the range of 1 to 10 mg daily were used. The mean dosage employed
was approximately 5 to 6 mg daily. Among the approximately 1700 patients participating in the
panic disorder development program, about 300 received XANAX in dosages of greater than 7
mg/day, including approximately 100 patients who received maximum dosages of greater than 9
mg/day. Occasional patients required as much as 10 mg a day to achieve a successful response.
5.3:Dose Titration
Treatment may be initiated with a dose of 0.5 mg three times daily. Depending on the response,
the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg per day.
Slower titration to the dose levels greater than 4 mg/day may be advisable to allow full
expression of the pharmacodynamic effect of XANAX. To lessen the possibility of interdose
symptoms, the times of administration should be distributed as evenly as possible throughout the
waking hours, that is, on a three or four times per day schedule.
Generally, therapy should be initiated at a low dose to minimize the risk of adverse responses in
patients especially sensitive to the drug. Dose should be advanced until an acceptable therapeutic
response (ie, a substantial reduction in or total elimination of panic attacks) is achieved,
intolerance occurs, or the maximum recommended dose is attained.
5.4:Dose Maintenance
For patients receiving doses greater than 4 mg/day, periodic reassessment and consideration of
dosage reduction is advised. In a controlled postmarketing dose-response study, patients treated
with doses of XANAX greater than 4 mg/day for 3 months were able to taper to 50% of their
total maintenance dose without apparent loss of clinical benefit. Because of the danger of
withdrawal, abrupt discontinuation of treatment should be avoided..
5.6:Dose Reduction
In all patients, dosage should be reduced gradually when discontinuing therapy or when
decreasing the daily dosage. Although there are no systematically collected data to support a
specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more
than 0.5 mg every three days. Some patients may require an even slower dosage reduction.
5.7:Dosing in Special Populations
In elderly patients, in patients with advanced liver disease or in patients with debilitating disease,
the usual starting dose is 0.25 mg, given two or three times daily. This may be gradually
increased if needed and tolerated. The elderly may be especially sensitive to the effects of
benzodiazepines. If side effects occur at the recommended starting dose, the dose may be
lowered.
6. DOSE ADJUSTMENT:
Patients with debilitating disease (e.g., severe pulmonary disease):
Immediate-release tablets/ODTs:
Initial dose: 0.25 mg orally 2 or 3 times a day
Extended-release tablets:
Initial dose: 0.5 mg orally once a day
7. ADMINISTRATION GUIDELINES:
1. 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.
2. 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.
3. Inform your physician if you are nursing.
4. Until you experience how this medication affects you, do not drive a car or operate
potentially dangerous machinery, etc.
5. 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.
6. Do not stop taking this medication abruptly or decrease the dose without consulting your
physician, since withdrawal symptoms can occur.
The use of XANAX at doses greater than 4 mg/day, often necessary to treat panic disorder, is
accompanied by risks that you need to carefully consider. When used at doses greater than 4
mg/day, which may or may not be required for your treatment, XANAX has the potential to
cause severe emotional and physical dependence in some patients and these patients may find it
exceedingly difficult to terminate treatment. In two controlled trials of 6 to 8 weeks duration
where the ability of patients to discontinue medication was measured, 7 to 29% of patients
treated with XANAX did not completely taper off therapy. In a controlled postmarketing
discontinuation study of panic disorder patients, the patients treated with doses of XANAX
greater than 4 mg/day had more difficulty tapering to zero dose than patients treated with less
than 4 mg/day. In all cases, it is important that your physician help you discontinue this
medication in a careful and safe manner to avoid overly extended use of XANAX.
In addition, the extended use at doses greater than 4 mg/day appears to increase the incidence
and severity of withdrawal reactions when XANAX is discontinued. These are generally minor
but seizure can occur, especially if you reduce the dose too rapidly or discontinue the medication
abruptly. Seizure can be life-threatening.
Drowsiness;
Tired feeling;
Muscle weakness; or
Loss of coordination.
Suppression of REM sleep and Slow wave sleep
Weak or shallow breathing;
Severe drowsiness or feeling like you might pass out;
Depressed mood, thoughts of suicide or hurting yourself;
Confusion, hallucinations;
Anxiety, panic attacks, trouble sleeping;
Hyperactivity aggitation, aggression, hostility;
Unusual risk-taking behavior; or
New or worsening seizures.
The sedative effects of alprazolam may last longer in older adults. Accidental falls are common
in elderly patients who take diazepam,. Use caution to avoid falling or accidental injury while
you are taking this medicine. Emergency medical help if you have signs of an allergic reaction to
alprazolam,: difficult breathing; swelling of your face, lips, tongue, or throat
8.2:Adverse Effects:
Alprazolam and other benzodiazepine can cause tolerance, physical dependence, substance use
disorder and benzodiazepine withdrawal syndrome
People with a history of alcohol or drug abuse or dependence.Alprazolam increases craving for
alcohol in problem alcohol consumers. Alprazolam also increases the volume of alcohol
consumed by problem drinkers.
Withdrawal Syndrom: Withdrawal symptoms can occur from standard dosages and also after
short-term use, and can range from insomnia and anxiety to more serious symptoms, including
seizures and psychosis. Withdrawal symptoms can sometimes resemble pre-existing conditions
and be misdiagnosed. Alprazolam may produce less intense withdrawal symptoms due to its long
elimination half life.
9.DRUG INTERACTION:
Fluoxetine
Propoxyphene
Oral Contraceptives
Carbamazepine can increase alprazolam metabolism and therefore can decrease plasma levels of
alprazolam.
10. TOXICOLOGY:
Although not usually fatal when taken alone, a alprazolam overdose is considered a medical
emergency and generally requires the immediate attention of medical personnel.
Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring
spoon or medicine cup. Do not use not a kitchen spoon. If you do not have a dose-measuring
device, ask your pharmacist for one.Alprazolam should be used for only a short time. Do not
take this medicine for longer than 4 months without your doctor's advice.Do not stop using this
medicine suddenly, or you could have increased seizures or unpleasant withdrawal symptoms.
Ask your doctor how to safely stop using this medicine.Call your doctor at once if you feel that
this medicine is not working as well as usual, or if you think you need to use more than usual.
Store at room temperature away from moisture, heat, and light. Keep track of your medicine.
Alprazolam is a drug of abuse and you should be aware if anyone is using your medicine
improperly or without a prescription.
Patients should be advised against the simultaneous ingestion of alcohol and other CNS-
depressant drugs during alprazolam therapy. As is true of most CNS-acting drugs, patients
receiving diazepam should be cautioned against engaging in hazardous occupations requiring
complete mental alertness, such as operating machinery or driving a motor vehicle.
13. REFERENCES:
1. Basic & Clinical Pharmacology written by G.Katzung and J.Trevor 12th edition page 389-400
2. British Pharmacopoeia.
4. https://en.wikipedia.org/wiki/Alprazolam#Chemistry