Active ingredient Alprazolam interacts in the following cases:

CYP3A4 Inducers

Since alprazolam is metabolized by CYP3A4, inducers of this enzyme may enhance the metabolism of alprazolam. Interactions involving HIV protease inhibitors (e.g. ritonavir) and alprazolam are complex and time dependent. Short term, low doses of ritonavir resulted in a large impairment of alprazolam clearance, prolonged its elimination half-life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose-adjustment or discontinuation of alprazolam.


The concomitant use of sedative medicines such as benzodiazepines or related drugs such as alprazolam with opioids increases the risk of sedation, respiratory depression, coma and death because of additive central nervous system (CNS) depressant effect. The dosage and duration of concomitant use should be limited.

Antipsychotics, hypnotics, anxiolytics, antidepressants, anti-epileptics, anaesthetics, sedative antihistamines

Alprazolam should be used with caution when combined with CNS depressants. Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines. In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychic dependence.


Increased digoxin concentrations have been reported when alprazolam was given, especially in elderly (>65 years of age). Patients who receive alprazolam and digoxin should therefore be monitored for signs and symptoms related to digoxin toxicity.

Fluoxetine, propoxyphene, oral contraceptives, sertraline, diltiazem, macrolide antibiotics

Caution is recommended when alprazolam is co-administered with fluoxetine, propoxyphene, oral contraceptives, sertraline, diltiazem, or macrolide antibiotics such as erythromycin, clarithromycin and troleandomycin.

Nefazodone, fluvoxamine, cimetidine

The co-administration of nefazodone or fluvoxamine increases the AUC of alprazolam by approximately 2-fold. Caution and consideration of dose reduction is recommended when alprazolam is co-administered with nefazodone, fluvoxamine and cimetidine.


The data concerning teratogenicity and effects on postnatal development and behavior following benzodiazepine treatment are inconsistent. A large amount of data based on cohort studies indicate that first trimester exposure to benzodiazepine is not associated with an increase in the risk of major malformation. However, some early case-control epidemiological studies have found a twofold increased risk of oral clefts.

Benzodiazepine treatment at high dose, during the second and/or the third trimester of pregnancy, has revealed a decrease of fetal active movements and a variability of fetal cardiac rhythm.

When treatment has to be administered for medical reasons during the last part of pregnancy, even at low doses, floppy infant syndrome such as axial hypotonia, sucking troubles leading to a poor weight gain may be observed. These signs are reversible but they may last from 1 up to 3 weeks, according to the half-life of the product. At high doses, respiratory depression or apnoea and hypothermia in newborn may appear. Moreover, neonatal withdrawal symptoms with hyper excitability, agitation and tremor may be observed a few days after birth, even if no floppy infant syndrome is observed. The apparition of withdrawal symptoms after birth depends on the half-life of the substance.

Alprazolam should not be used during pregnancy unless the clinical condition of the woman requires treatment with alprazolam. If alprazolam is used during pregnancy, or of the patient becomes pregnant while taking alprazolam, the patient should be apprised of the potential hazard to the fetus.

If alprazolam treatment is necessary during last part of pregnancy, high doses should be avoided and withdrawal symptoms and/or floppy infant syndrome should be monitored in newborn.

Nursing mothers

Alprazolam is excreted in breast milk at low level. However, alprazolam is not recommended during breast-feeding.

Effects on ability to drive and use machines

Sedation, amnesia, impaired concentration and impaired muscle function may adversely affect the ability to drive and use machines. If insufficient sleep occurs, the likelihood of impaired alertness may be increased.

These effects are potentiated by alcohol.

Patients should be cautioned about operating motor vehicles or engaging in other dangerous activities while taking alprazolam.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

  • The medicine is likely to affect your ability to drive
  • Do not drive until you know how the medicine affects you
  • It is an offence to drive while under the influence of this medicine
  • However, you would not be committing an offence (called ‘statutory defence’) if:
    • The medicine has been prescribed to treat a medical or dental problem and
    • You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
    • It was not affecting your ability to drive safely

Adverse reactions

Adverse events, if they occur, are generally observed at the beginning of therapy and usually disappear upon continued medication or decreased dosage.

The following undesirable effects have been observed and reported during treatment with alprazolam with the following frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Endocrine disorders

Not known: Hyperprolactinaemia*

Metabolism and nutrition disorders

Common: Decreased appetite

Psychiatric disorders

Very common: Depression

Common: Confusional state, disorientation, libido decreased, anxiety, insomnia, nervousness, libido increased*

Uncommon: Mania*, hallucination*, anger*, agitation*

Not known: Hypomania*, aggression*, hostility*, thinking abnormal*, psychomotor hyperactivity*

Nervous system disorders

Very common: Sedation, somnolence, ataxia, memory impairment, dysarthria, dizziness, headache

Common: Balance disorder, coordination abnormal, disturbance in attention, hypersomnia, lethargy, tremor

Uncommon: Amnesia

Not Known: Autonomic nervous system imbalance*, dystonia*

Eye disorders

Common: Vision blurred

Gastrointestinal disorders

Very common: Constipation, dry mouth

Common: Nausea

Not known: Gastrointestinal disorder*

Hepatobiliary disorders

Not known: Hepatitis*, hepatic function abnormal*, jaundice*

Skin and subcutaneous tissue disorders

Common: Dermatitis*

Not Known: Angioedema*, photosensitivity reaction*

Musculoskeletal and connective tissue disorders

Uncommon: Muscular weakness

Renal and urinary disorders

Uncommon: Incontinence*

Not known: Urinary retention*

Reproductive system and breast disorders

Common: Sexual dysfunction*

Uncommon: Menstruation irregular*

General disorders and administration site conditions

Very common: Fatigue, irritability

Not Known: Oedema peripheral*


Common: Weight increased, weight decreased

Not known: Intraocular pressure increased*

* ADR identified post-marketing

Withdrawal symptoms have occurred following rapid decrease or abrupt discontinuance of benzodiazepines including alprazolam. These can range from mild dysphoria and insomnia to a major syndrome, which may include abdominal and muscle cramps, vomiting, sweating, tremor and convulsions. In addition, withdrawal seizures have occurred upon rapid decrease or abrupt discontinuation of therapy with alprazolam.


Anterograde amnesia may occur at therapeutic dosages, the risk increasing at higher dosages. Amnesic effects may be associated with inappropriate behaviour.


Pre-existing depression may be unmasked during benzodiazepine use.

Psychiatric and paradoxical reactions

Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine-like agents. They may be quite severe with this product. They are more likely to occur in children and the elderly.

In many of the spontaneous case reports of adverse behavioural effects, patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Patients who have borderline personality disorder, a prior history of violent or aggressive behaviour, or alcohol or substance abuse may be at risk of such events. Instances of irritability, hostility and intrusive thoughts have been reported during discontinuance of alprazolam in patients with post-traumatic stress disorder.


Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena. Psychic dependence may occur. Abuse of benzodiazepines has been reported.

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