Active ingredients: Oxazepam
Serpax 15 mg tablets
Serpax 30 mg tablets
Why is Serpax used? What is it for?
Pharmacotherapeutic group
Anxiolytics, benzodiazepine derivatives
Therapeutic indications
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome. Benzodiazepines are indicated only when the disorder is severe, disabling and subjects the subject to severe distress.
Contraindications When Serpax should not be used
Serpax is contraindicated in patients with:
- Hypersensitivity to the active substance, to benzodiazepines or to any of the excipients.
- Sleep apnea syndrome.
- Severe respiratory insufficiency.
- Myasthenia gravis.
- Severe hepatic insufficiency.
- Known or suspected pregnancy
- Breastfeeding (see pregnancy and lactation).
- Pediatric age.
Precautions for use What you need to know before taking Serpax
Specific groups of patients
The elderly should take a reduced dose (see "Dose, method and time of administration"). Likewise, a lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression.
Due to the muscle relaxant effect in the elderly there is a risk of falls and consequently of fractures.
Patients with severe hepatic impairment may have a reduced ability to metabolise oxazepam via glucuronidation.
Patients with impaired hepatic or renal function should be monitored frequently and the dosage should be carefully adjusted to the individual patient's response. Lower dosages may be sufficient in these patients.
Benzodiazepines are contraindicated in patients with severe hepatic insufficiency and / or encephalopathy as, like all benzodiazepines, they can precipitate hepatic encephalopathy.
Caution should be used in the treatment of patients with narrow-angle glaucoma.
Benzodiazepines are not recommended for the primary treatment of psychotic illness. Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide can be precipitated in such patients). In these patients, large amounts of Serpax should be avoided.
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.
Pediatric use
Benzodiazepines should not be given to children without carefully assessing the actual need for treatment; the duration of treatment should be as short as possible.
Interactions Which drugs or foods can change the effect of Serpax
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines. (see section 4.7).
Association with central nervous system (CNS) depressants: the central depressive effect may be enhanced in cases of concomitant use with alcohol, barbiturates, antipsychotics (neuroleptics), hypnotics / sedatives, anxiolytics, antidepressants, narcotic analgesics, antiepileptics, anticonvulsants, sedative anesthetics and antihistamines In the case of narcotic analgesics an increase in euphoria may occur, leading to an increase in psychic dependence.
Administration of theophylline and aminophylline may reduce the sedative effects of benzodiazepines, including Serpax.
Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines. To a lesser extent, this also applies to benzodiazepines which are metabolized only by conjugation.
Interactions in laboratory analyzes
No interferences in laboratory tests have been reported or identified with the use of Serpax. However, oxazepam has been reported to impair cortisol production. A dexamethasone suppression test may be impaired if Serpax was administered prior to testing.
Warnings It is important to know that:
The use of benzodiazepines, including Serpax, can lead to life-threatening respiratory depression.
Serious anaphylactic / anaphylactoid reactions have been reported with the use of benzodiazepines. Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of benzodiazepines. Some patients taking benzodiazepines have have had additional symptoms such as dyspnoea, throat closure, or nausea and vomiting. Some patients have required treatment in the emergency room. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur which may be fatal.
Patients who develop angioedema after treatment with benzodiazepines should not be re-treated with the drug.
Serpax should be used with caution in patients with impaired respiratory functions (e.g. chronic pulmonary obstruction, sleep apnea syndrome).
Patients should be advised that as their tolerance to alcohol or other CNS depressant drugs decreases with Serpax, they must either avoid these substances altogether or reduce their doses.
The need for continued Serpax therapy should be evaluated periodically.
Benzodiazepine therapy should be discontinued gradually.
Serpax is only indicated if the disorder cannot be resolved with non-pharmacological therapy, and is serious, disabling and such as to cause profound malaise. Anxiety and tension associated with contingent phenomena of daily life do not normally require treatment with an anxiolytic.
Anxiety can be a symptom of several other disorders. The possibility that the anxiety may be related to a latent physical or psychiatric disorder for which there is a more specific treatment should be considered.
Pre-existing depression may develop or worsen during treatment with benzodiazepines, including Serpax (see "Side Effects"). The use of benzodiazepines can unmask suicidal tendencies in depressed patients and they should not be administered without adequate antidepressant therapy.
Some patients on benzodiazepines have developed blood dyscrasia, and some have had elevations in liver enzymes. When prolonged therapy is clinically necessary, periodic haematological and liver function checks are recommended.
Although hypotension has only rarely occurred, benzodiazepines should be administered with caution to patients in whom a drop in blood pressure can lead to cardio- or cerebro-vascular complications. This is particularly important in elderly patients.
Tolerance
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Dependence
The use of benzodiazepines, including Serpax, can lead to the development of physical and psychological dependence on these drugs. When used at the recommended doses in the short-term treatment of anxiety, the potential for Serpax to induce dependence is low. The risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of alcohol, drug or drug abuse or with marked personality disorders. Therefore, use in drug addicted patients or alcoholics should be avoided. In general, benzodiazepines should only be prescribed for short periods (2-4 weeks). Continuous long-term use is not recommended. Withdrawal symptoms (eg rebound insomnia) may occur following discontinuation of the recommended dosage after one week of therapy. Abrupt discontinuation of treatment should be avoided and an extended period of therapy should be followed by a gradual dose reduction program.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headache, muscle aches, extreme anxiety, tension, restlessness, confusion, irritability, rebound phenomena, dizziness, dysphoria.
In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, tinnitus, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact / perceptual changes, involuntary movements, vomiting, nausea, diarrhea, loss of appetite, hallucinations / delirium, tremor, abdominal cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, dizziness, hyper-reflexia, short-term memory loss, hyperthermia, seizures or convulsions. Seizures / seizures may be more common in patients with pre-existing seizure disorders or who use other drugs that lower the seizure threshold, such as antidepressants.
Other symptoms are: depression, insomnia, sweating.
Rebound insomnia and anxiety: A transient syndrome may occur on discontinuation of treatment in which symptoms that led to treatment with benzodiazepines recur in an aggravated form. This syndrome may be accompanied by other reactions, including mood changes, anxiety, restlessness or sleep disorders
Withdrawal symptoms, especially the more severe ones, are more common in those patients who have received high doses over a long period of time; however, they can also occur after discontinuation of benzodiazepines taken continuously at therapeutic dosages, especially if the suspension occurs abruptly.
Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested. There is evidence of developing tolerance to the sedative effects of benzodiazepines.
Serpax may have potential for abuse especially in patients with a history of drug and / or alcohol abuse
Duration of treatment
The duration of treatment should be as short as possible (see dose, method and time of administration) depending on the indication, but should not exceed eight to twelve weeks, including the gradual withdrawal period. The extension of therapy beyond these periods should not occur without reassessment of the clinical situation. It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased.
It is also important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about these symptoms should they occur when the drug is discontinued.
Amnesia
Benzodiazepines can induce anterograde amnesia or memory impairment. This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk it must be ensured that patients can have an uninterrupted sleep of 7-8 hours (see side effects).
Psychiatric and paradoxical reactions
Paradoxical reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes, anxiety states, hostility, excitement, sleep disturbances / insomnia, have occasionally been reported with the use of benzodiazepines. sexual arousal, sedation, fatigue, drowsiness, ataxia, confusion, depression, unmasking of depression, dizziness, changes in libido, impotence, decreased orgasm. Should this occur, use of the drug should be discontinued. Such reactions are more frequent in children and the elderly.
Fertility, pregnancy and breastfeeding
Pregnancy
Ask your doctor or pharmacist for advice before taking any medicine.
Benzodiazepines should not be used during pregnancy, especially in the first and third trimester.
If the product is prescribed to a woman of childbearing age, she should contact her doctor, both if she intends to become pregnant and if she suspects that she is pregnant, regarding discontinuation of the medicine.
Taking benzodiazepines during pregnancy can cause fetal harm. An increased risk of congenital malformations associated with the use of anxiolytic agents, such as chlordiazepoxide, diazepam and meprobamate, during the first trimester of pregnancy, has been suggested in several studies.
In humans, blood levels obtained from the umbilical cord indicate that benzodiazepines and their glucuronides pass through the placenta. If, for serious medical reasons, the product is administered during the last period of pregnancy, or during labor at high doses , effects on the newborn may occur. Symptoms such as hypoactivity, hypotonia, hypothermia, respiratory depression, apnea, nutritional problems and metabolic responses altered by decreased resistance to cold have been reported in neonates whose mothers used benzodiazepines during late pregnancy or during delivery.
Additionally, infants born to mothers who have taken benzodiazepines chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Feeding time
Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers unless the expected benefit to the woman outweighs the potential risk to the newborn.
Sedation and inability to take breast milk occurred during lactation in infants whose mothers were taking benzodiazepines. Infants born to such mothers should be observed for pharmacological effects (including sedation and irritability
Fertility
The effects of oxazepam on human fertility are unknown.
Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive and use machines. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see interactions). As with all patients receiving CNS-acting drugs, patients should be advised not to operate hazardous machinery and not to drive until they are certain they are not drowsy or light headed by Serpax.
Important information about some of the ingredients
The medicine contains lactose so in case of ascertained intolerance to sugars contact your doctor before taking the medicine.
Dosage and method of use How to use Serpax: Dosage
Treatment should be as short as possible. The patient should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including a gradual withdrawal period.
In certain cases, extension beyond the maximum treatment period may be necessary, in which case this should not be done without reassessment of the patient's condition.
Treatment should be started with the lowest recommended dose.
The maximum dose should not be exceeded.
The dosage and duration of treatment must be individually adjusted. The lowest effective dose should be prescribed for the shortest time possible.
Treatment should be discontinued gradually.
For mild to moderate anxiety the usual dosage is 15 mg, 3 or 4 times a day.
For severe anxiety syndromes, or anxiety associated with depression, the usual dosage is 15-30 mg, 3 or 4 times a day.
Elderly or debilitated patients, or patients with impaired hepatic or renal function or with chronic respiratory failure generally require lower or less frequent doses. These patients should be monitored frequently, and dosage should be carefully tailored to individual response. Patients with severe hepatic impairment may have an impaired ability to metabolise oxazepam via glucuronidation.
For elderly or debilitated patients, the starting dosage is 15 mg, 1 or 2 times a day. If necessary, the dosage can be cautiously increased to 15 mg, 3 or 4 times a day.
Overdose What to do if you have taken too much Serpax
As with other benzodiazepines, an overdose is not expected to be life-threatening unless concomitant other CNS depressants (including alcohol) are taken.
In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered.
Symptoms:
Overdosage of benzodiazepines usually results in varying degrees of central nervous system depression ranging from clouding to coma. In mild cases, symptoms include drowsiness, confusion, dysarthria, and lethargy. In more severe cases (such as those that may occur following massive suicide intake) symptoms may include ataxia, hypotonia, hypotension, hypnosis, paradoxical reactions, CNS depression, cardiovascular depression, respiratory depression, 1 ° -3 coma Degree and death.
Treatment:
Following an overdose of benzodiazepines for oral use, vomiting should be induced (within one "hour) if the patient is conscious or gastric lavage undertaken, immediately after ingestion, with respiratory protection if the patient is deprived. of knowledge or in patients presenting with symptoms, followed, if appropriate, by general resuscitation practices, monitoring of vital signs and close observation of the patient. Where there is a risk of aspiration, induction of vomiting is not recommended
If no improvement is observed with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy.
Hypotension, although unlikely, can be controlled with norepinephrine. Serpax is poorly dialyzable.
The benzodiazepine antagonist, flumazenil, can be used in hospitalized patients as an adjunct to the appropriate treatment of a benzodiazepine overdose, not as a replacement. Before using it you need to consult the product information. Physicians should be aware of the risk of seizures in association with flumazenil treatment, particularly in those who have been using benzodiazepines for a long time and in case of overdose of cyclic antidepressants.
In case of accidental ingestion / intake of an excessive dose of SERPAX, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of SERPAX, ask your doctor or pharmacist.
Side Effects What are the side effects of Serpax
Like all medicines, SERPAX can cause side effects, although not everybody gets them.
Within the MedDRA System Organ Class, adverse reactions are listed by frequency (number of patients expected to experience adverse reactions) using the following categories:
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 (frequency cannot be estimated from the available data)
Due to the muscle relaxant effect in the elderly there is a risk of falls and consequently of fractures.
The effects of benzodiazepines on the CNS are dose dependent. High doses result in more severe CNS depression.
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see "Special Warnings").
Depression
A pre-existing depressive state may be unmasked during the use of benzodiazepines.
Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes.
Such reactions can be quite severe. They are more likely in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) may lead to the development of physical dependence; discontinuation of therapy may result in rebound or withdrawal phenomena (see Special warnings). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date indicated on the package
The expiry date indicated refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date indicated on the package
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children
Composition
Serpax 15 mg tablets
Each tablet contains:
Active ingredient: oxazepam 15.00 mg.
Excipients: lactose, magnesium stearate, corn starch, pregelatinised starch.
Serpax 30 mg tablets
Each tablet contains:
Active ingredient: oxazepam 30.00 mg.
Excipients: lactose, microcrystalline cellulose, polacrilin potassium, magnesium stearate.Tablets.
Serpax 15 mg tablets - 20 tablets
Serpax 30 mg tablets - 20 tablets
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SERPAX TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Serpax 15 mg tablets
Each tablet contains:
Active ingredient: oxazepam 15.00 mg.
Serpax 30 mg tablets
Each tablet contains:
Active ingredient: oxazepam 30.00 mg.
For the full list of excipients see section 6.1
03.0 PHARMACEUTICAL FORM
Divisible tablets
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome.
Benzodiazepines are indicated only when the disorder is severe, disabling and subjects the subject to severe distress.
04.2 Posology and method of administration
Treatment should be as short as possible. The patient should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including a gradual withdrawal period.
In certain cases, extension beyond the maximum treatment period may be necessary, in which case this should not be done without reassessment of the patient's condition.
Treatment should be started with the lowest recommended dose.
The maximum dose should not be exceeded.
The dosage and duration of treatment must be individually adjusted.
The lowest effective dose should be prescribed for the shortest time possible.
Treatment should be discontinued gradually.
For mild to moderate anxiety the usual dosage is 15 mg, 3 or 4 times a day.
For severe anxiety syndromes, or anxiety associated with depression, the usual dosage is 15-30 mg 3 or 4 times a day.
Elderly or debilitated patients, or patients with impaired hepatic or renal function or with chronic respiratory failure generally require lower or less frequent doses. These patients should be monitored frequently, and dosage should be carefully tailored to individual response. Patients with severe hepatic impairment may have an impaired ability to metabolise oxazepam via glucuronidation (see section 5.2).
For elderly or debilitated patients, the starting dosage is 15 mg, 1 or 2 times a day. If necessary, the dosage can be cautiously increased to 15 mg, 3 or 4 times a day.
04.3 Contraindications
Serpax is contraindicated in patients with:
Hypersensitivity to the active substance, to benzodiazepines or to any of the excipients.
Sleep apnea syndrome.
Severe respiratory insufficiency.
Myasthenia gravis.
Severe hepatic insufficiency.
Known or suspected pregnancy - Lactation (see section 4.6).
Pediatric age.
04.4 Special warnings and appropriate precautions for use
The use of benzodiazepines, including Serpax, can lead to life-threatening respiratory depression.
Serious anaphylactic / anaphylactoid reactions have been reported with the use of benzodiazepines. Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of benzodiazepines. Some patients taking benzodiazepines have have had additional symptoms such as dyspnoea, throat closure, or nausea and vomiting. Some patients have required treatment in the emergency room. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur which may be fatal.
Patients who develop angioedema after treatment with benzodiazepines should not be re-treated with the drug.
Serpax should be used with caution in patients with impaired respiratory functions (eg chronic pulmonary obstruction, sleep apnea syndrome).
Patients should be advised that as their tolerance to alcohol or other central nervous system (CNS) depressant drugs decreases with Serpax, they must either avoid these substances altogether or reduce their doses.
The need for continued Serpax therapy should be evaluated periodically.
Benzodiazepine therapy should be discontinued gradually.
Serpax is only indicated if the disorder cannot be resolved with non-pharmacological therapy, and is serious, disabling and such as to cause profound malaise. Anxiety and tension associated with contingent phenomena of daily life do not normally require treatment with an anxiolytic.
Anxiety can be a symptom of several other disorders. The possibility that the anxiety may be related to a latent physical or psychiatric disorder for which there is a more specific treatment should be considered.
Pre-existing depression may emerge or worsen during treatment with benzodiazepines, including Serpax (see section 4.8). The use of benzodiazepines can unmask suicidal tendencies in depressed patients and they should not be administered without adequate antidepressant therapy.
Some patients on benzodiazepines have developed blood dyscrasia, and some have had elevations in liver enzymes. When prolonged therapy is clinically necessary, periodic haematological and liver function checks are recommended.
Although hypotension has only rarely occurred, benzodiazepines should be administered with caution to patients in whom a drop in blood pressure can lead to cardio- or cerebro-vascular complications. This is particularly important in elderly patients.
Tolerance
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Dependence
The use of benzodiazepines, including Serpax, can lead to the development of physical and psychological dependence on these drugs. When used at the recommended doses in the short-term treatment of anxiety, the potential for Serpax to induce dependence is low. The risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of alcohol, drug or drug abuse or with marked personality disorders. Therefore, use in drug addicted patients or alcoholics should be avoided. In general, benzodiazepines should only be prescribed for short periods (2-4 weeks). Continuous long-term use is not recommended.
Withdrawal symptoms (eg rebound insomnia) may occur following discontinuation of the recommended dosage after only one week of therapy. Abrupt discontinuation of treatment should be avoided and an extended period of therapy should be followed by a gradual dose reduction program.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headache, muscle aches, extreme anxiety, tension, restlessness, confusion, irritability, rebound phenomena, dizziness, dysphoria.
In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, tinnitus, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact / perceptual changes, involuntary movements, vomiting, nausea, diarrhea, loss of appetite, hallucinations / delirium, tremor, abdominal cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, dizziness, hyper-reflexia, short-term memory loss, hyperthermia, seizures or convulsions. Seizures / seizures may be more common in patients with pre-existing seizure disorders or who use other drugs that lower the seizure threshold, such as antidepressants.
Other symptoms are: depression, insomnia, sweating.
Rebound insomnia and anxiety: A transient syndrome in which symptoms leading to benzodiazepine treatment recur in an aggravated form may occur on discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or disturbances sleep.
Withdrawal symptoms, especially the more severe ones, are more common in those patients who have received high doses over a long period of time; however, they can also occur after discontinuation of benzodiazepines taken continuously at therapeutic dosages, especially if the suspension occurs abruptly.
Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested.
There is evidence of developing tolerance to the sedative effects of benzodiazepines.
Serpax may have potential for abuse especially in patients with a history of drug and / or alcohol abuse.
Duration of treatment
The duration of treatment should be as short as possible (see section 4.2) depending on the indication, but should not exceed eight to twelve weeks, including the gradual withdrawal period. Extension of therapy beyond these periods should not occur without re-evaluation of the clinical situation. It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased.It is also important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about these symptoms should they occur when the drug is discontinued.
Amnesia
Benzodiazepines can induce anterograde amnesia or memory impairment.
This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk it must be ensured that patients can have an uninterrupted sleep of 7-8 hours (see section 4.8).
Psychiatric and paradoxical reactions
Paradoxical reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes, anxiety states, hostility, excitement, sleep disturbances / insomnia, have occasionally been reported with the use of benzodiazepines. sexual arousal, sedation, fatigue, drowsiness, ataxia, confusion, depression, unmasking of depression, dizziness, changes in libido, impotence, decreased orgasm. Should this occur, use of the drug should be discontinued. Such reactions are more frequent in children and the elderly.
Specific groups of patients
The elderly should take a reduced dose (see section 4.2). Likewise, a lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression.
Due to the muscle relaxant effect in the elderly there is a risk of falls and consequently of fractures.
Patients with severe hepatic impairment may have a reduced ability to metabolise oxazepam via glucuronidation (see section 5.2).
Patients with impaired hepatic or renal function should be monitored frequently and the dosage should be carefully adjusted to the individual patient's response. Lower dosages may be sufficient in these patients.
Benzodiazepines are contraindicated in patients with severe hepatic insufficiency and / or encephalopathy as, like all benzodiazepines, they can precipitate hepatic encephalopathy.
Caution should be used in the treatment of patients with narrow-angle glaucoma.
Benzodiazepines are not recommended for the primary treatment of psychotic illness. Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide can be precipitated in such patients). In these patients, large amounts of Serpax should be avoided.
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.
Pediatric use
Benzodiazepines should not be given to children without carefully evaluating the actual need for treatment; the duration of treatment should be as short as possible.
Important information about some of the excipients.
The medicinal product contains lactose and is therefore not suitable for individuals with lactase deficiency, galactosemia or glucose / galactose malabsorption syndrome.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines (see section 4.7).
Association with CNS depressants: The central depressive effect may be enhanced in cases of concomitant use with alcohol, barbiturates, antipsychotics (neuroleptics), hypnotics / sedatives, anxiolytics, antidepressants, narcotic analgesics, antiepileptics, anticonvulsants, anesthetics and sedative antihistamines. In the case of narcotic analgesics, an increase in euphoria can occur, leading to an increase in psychic dependence.
Administration of theophylline and aminophylline may reduce the sedative effects of benzodiazepines, including Serpax.
Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines. To a lesser extent, this also applies to benzodiazepines which are metabolized only by conjugation.
Interactions in laboratory analyzes
No interferences in laboratory tests have been reported or identified with the use of Serpax. However, oxazepam has been reported to impair cortisol production. A dexamethasone suppression test may be impaired if Serpax was administered prior to testing.
04.6 Pregnancy and lactation
Pregnancy
Benzodiazepines should not be used during pregnancy, especially in the first and third trimester.
If the product is prescribed to a woman of childbearing age, she should contact her doctor, both if she intends to become pregnant and if she suspects that she is pregnant, regarding discontinuation of the medicine.
Taking benzodiazepines during pregnancy can cause fetal harm. An increased risk of congenital malformations associated with the use of anxiolytic agents, such as chlordiazepoxide, diazepam and meprobamate, during the first trimester of pregnancy, has been suggested in several studies.
In humans, blood levels obtained from the umbilical cord indicate that benzodiazepines and their glucuronides pass through the placenta. If, for serious medical reasons, the product is administered during the last period of pregnancy, or during labor at high doses , effects on the newborn may occur. Symptoms such as hypoactivity, hypotonia, hypothermia, respiratory depression, apnea, nutritional problems and metabolic responses altered by decreased resistance to cold have been reported in neonates whose mothers used benzodiazepines during late pregnancy or during delivery.
Additionally, infants born to mothers who have taken benzodiazepines chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Feeding time
Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers unless the expected benefit to the woman outweighs the potential risk to the newborn.
Sedation and inability to take breast milk have occurred during lactation in infants whose mothers were taking benzodiazepines. Infants born to such mothers should be observed for pharmacological effects (including sedation and irritability).
Fertility
The effects of oxazepam on human fertility are unknown.
04.7 Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive and use machines. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see section 4.5). As with all patients receiving CNS-acting drugs, patients should be advised not to operate hazardous machinery and not to drive until they are certain they are not drowsy or light headed by Serpax.
04.8 Undesirable effects
As part of the MedDRA System Organ Classification, reactions
adverse events are listed by frequency (number of patients expected to be
present adverse reactions) using the following categories:
Very common (≥1 / 10)
Common (≥1 / 100,
Uncommon (≥1 / 1,000 to
Rare (≥1 / 10,000,
Very rare (
Not known (frequency cannot be estimated from the available data)
Table: Frequency of undesirable effects
Due to the muscle relaxant effect in the elderly there is a risk of falls and consequently of fractures.
The effects of benzodiazepines on the CNS are dose-dependent. High dosages result in more severe CNS depression.
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see section 4.4).
Depression
A pre-existing depressive state may be unmasked during the use of benzodiazepines.
Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes.
Such reactions can be quite severe. They are more likely in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) may lead to the development of physical dependence; discontinuation of therapy may result in rebound or withdrawal phenomena (see section 4.4). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
04.9 Overdose
As with other benzodiazepines, an overdose is not expected to be life-threatening unless concomitant other CNS depressants (including alcohol) are taken.
In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered. Following an overdose of benzodiazepines for oral use, vomiting should be induced (within one "hour) if the patient is conscious. o Started gastric lavage, immediately after ingestion, with respiratory protection if the patient is unconscious or in patients presenting with symptoms, followed, if necessary, by general resuscitation practices, monitoring of vital signs and close observation of the patient. If there is a risk of aspiration, induction of vomiting is not recommended. If no improvement is observed with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy. Overdosage of benzodiazepines usually results in varying degrees of central nervous system depression ranging from clouding to coma. In mild cases, symptoms include drowsiness, confusion, dysarthria, and lethargy.
In more severe cases (such as those that may occur following massive suicide intake) symptoms may include ataxia, hypotonia, hypotension, hypnosis, paradoxical reactions, CNS depression, cardiovascular depression, respiratory depression, 1 ° -3 coma Degree and death.
Hypotension, although unlikely, can be controlled with noradrenaline.
Serpax is poorly dialyzable.
The benzodiazepine antagonist flumazenil can be used in hospitalized patients as an adjunct to the appropriate treatment of a benzodiazepine overdose, not as a replacement. Before using it you need to consult the product information. Physicians should be aware of the risk of seizures in association with flumazenil treatment, particularly in those who have been using benzodiazepines for a long time and in case of overdose of cyclic antidepressants.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anxiolytics, benzodiazepine derivatives
ATC code: N05BA04
Oxazepam (Serpax) is a 1,4 benzodiazepine having the following chemical name 7-chloro-1,3-dihydro-3 hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one.
Oxazepam is a white-cream to light yellow powder, practically odorless, almost insoluble in water and slightly soluble in alcohol and chloroform. The molecular weight is 286.7 and the melting point is between 205 ° -206 ° C.
Its structural formula is as follows:
Like all benzodiazepines, Serpax possesses anxiolytic and sedative properties.
The exact mechanism of action of benzodiazepines has not yet been elucidated; however, it appears that benzodiazepines act through various mechanisms. Benzodiazepines presumably exert their effects by binding to specific receptors at different sites within the central nervous system, or by enhancing the effects of benzodiazepines. effects of synaptic or presynaptic inhibition mediated by (-aminobutyric acid or directly influencing the mechanisms that generate the action potential.
05.2 "Pharmacokinetic properties
Serpax administered orally is rapidly and almost completely absorbed. Maximum plasma concentrations are reached approximately 2-3 hours after oral administration. The elimination half-life of Serpax in human plasma normally ranges from 4 to 15 hours. At clinically significant concentrations, Serpax is 95-98% bound to plasma proteins. Serpax is conjugated in the liver at the 3-hydroxy position and transformed into its inactive glucuronide Within 48 hours after oral administration, more than 70% of the dose is present in the urine in the form of glucuronide, which accounts for at least 95% of urinary excretion products. Serpax is not significantly hydroxylated and does not possess active metabolites. Serpax is not a substrate for the N-dealkylating enzymes of the cytochromic P-450 system. Multiple dose therapy does not lead to excessive drug accumulation in healthy subjects.
The kinetics of oxazepam are not clinically significantly affected by age. Some studies in elderly patients have reported a statistically significant increase in the elimination half-life of oxazepam compared to younger patients, but the total clearance was not significantly altered.
The glucuronidation and elimination kinetics of oxazepam remain relatively unaffected in the presence of mild to moderate compensated liver disease (acute viral hepatitis, cirrhosis). A study in patients with severe decompensated cirrhosis and encephalopathy showed a significant decrease in liver clearance. oxazepam. The mean elimination half-life (16.7 hours) was significantly prolonged compared to the control value (5.8 hours). The mean apparent clearance (0.55 ml / min. / Kg), the percentage of unbound drug (15.4%) and the clearance of unbound oxazepam (4.1 ml / min. / Kg) were significantly modified compared to the control values (1.19 ml / min. / Kg, 4.6 % and 25.4 ml / min. / kg, respectively). These results suggest decreased glucuronidation and elimination capacity of oxazepam in patients with decompensated liver disease and severe hepatic insufficiency.
Studies in patients with varying degrees of renal disease, including chronic renal failure and renal failure, have shown no clinically significant effect on total oxazepam clearance and mean steady state plasma levels compared to healthy subjects. Elimination of the inactive glucuronide was significantly reduced. In a study of patients with severe renal impairment on permanent hemodialysis, reduced clearance of unbound drug was found, although total oxazepam clearance was similar to that of subjects. of healthy controls. The amount of oxazepam recovered by dialysis was negligible.
05.3 Preclinical safety data
Toxicity
Serpax showed a very low acute toxicity with LD50 equal to (for oral administration): rat 6500 mg / kg; mouse 4500 mg / Kg. Numerous subacute and chronic toxicity tests have been conducted in different animal species in which Serpax has been shown to have very low toxicity.
Teratogenesis
Numerous tests conducted on different animal species would exclude teratogenic effects of oxazepam.
Carcinogenesis, mutagenesis
In a two-year carcinogenicity study, oxazepam was administered to rats with the diet.Male rats receiving 30 times the maximum human dose showed a statistical increase in benign thyroid follicular cell tumors, testicular interstitial cell adenomas and prostate adenomas in comparison to the control groups. In a previously published study it was reported that mice treated for 9 months with oxazepam doses of 35 to 100 times the human daily dose developed a dose-related increase in hepatic adenomas. In an independent microscope analysis of samples from this study, several of these tumors were classified as liver carcinomas. Another study reported a dose-related increase in liver adenomas or carcinomas in mice treated for up to two years with oxazepam doses equal to or greater than an average consumption of approximately 135 times the maximum daily human dose. The same study showed an "increased incidence of follicular thyroid cell adenomas in female B6C3F1 rats treated for two years with oxazepam doses equal to or greater than an average consumption of approximately 175 times the daily human dose. To date there is no evidence that the clinical use of oxazepam is associated with the onset of tumors.
Reports of in vitro mutagenicity with oxazepam have not reached conclusive results; in one study, oxazepam was found to be mutagenic in the Ames test on Salmonella typhimurium, while in a subsequent study conducted with and without metabolic activation, oxazepam was found to be non-mutagenic in none of the different Salmonella typhimurium strains, did it induce exchange of alleles or Chromosomal aberrations in Chinese Hamster ovary cell cultures. Another experiment with the Salmonella / microsome assay indicated that oxazepam is non-mutagenic in both the presence and absence of rat liver enzymatic activation.
Fertility Studies
Female rats that received a diet containing 0.05% or 0.75% oxazepam showed a significant decrease in the frequency of vaginal estrus. The effects of oxazepam on human fertility are unknown.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Serpax 15 mg tablets
Each tablet contains:
Excipients: lactose; magnesium stearate; cornstarch; pregelatinised starch.
Serpax 30 mg tablets
Each tablet contains:
Excipients: lactose; microcrystalline cellulose; polacrilin potassium; magnesium stearate.
06.2 Incompatibility
To date, no incompatibility is known.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Blisters (in PVC and aluminum)
Serpax 15 mg tablets - 20 tablets
Serpax 30 mg tablets - 20 tablets
06.6 Instructions for use and handling
See the information in section 4.2.
07.0 MARKETING AUTHORIZATION HOLDER
Meda Pharma S.p.A. Viale Brenta, 18 - 20139-Milan
08.0 MARKETING AUTHORIZATION NUMBER
SERPAX 15 mg tablets AIC n. 020835031
SERPAX 30 mg tablets AIC n. 020835043
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 1967
Authorization renewal: June 2010
10.0 DATE OF REVISION OF THE TEXT
March 2012
