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MEBARAL

 * Generic Name: mephobarbital
 * Brand Name: Mebaral
 * Drug Class: Anticonvulsants, Barbiturates

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 4/4/2022

home drugs a-z list mebaral (mephobarbital) drug

   
   
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DRUG SUMMARY

WHAT IS MEBARAL?

Mebaral (mephobarbital) is a barbiturate used as a sedative to treat anxiety,
tension, and apprehension (dreading or feeling uneasy about what you think may
happen). Mebaral is also used to treat seizures. Mebaral is available in generic
form.

WHAT ARE SIDE EFFECTS OF MEBARAL?

Common side effects of Mebaral include:

 *  drowsiness
 * dizziness
 * upset stomach
 * headache
 * memory or thinking problems
 * nervousness
 * agitation
 * nausea, or
 * vomiting

DOSAGE FOR MEBARAL

The adult dose of Mebaral for sedation is 32 to 100 mg; optimum dose, 50 mg,
three to four times daily. The average dose for adults to treat epilepsy is 400
mg to 600 mg daily.

WHAT DRUGS, SUBSTANCES, OR SUPPLEMENTS INTERACT WITH MEBARAL?

Mebaral may interact with blood thinners, doxycycline, griseofulvin,
phenobarbital, steroids, phenytoin, divalproex sodium, valproic acid, MAO
inhibitors, cold or allergy medicine, narcotics, sleeping pills, muscle
relaxers, and medicine for seizures, depression or anxiety. Tell your doctor all
medications and supplements you use.

MEBARAL DURING PREGNANCY OR BREASTFEEDING

During pregnancy, Mebaral should be used only when prescribed. It may harm a
fetus. Since untreated seizures are a serious condition that can harm both a
pregnant woman and her unborn baby, do not stop taking this medication unless
directed by your doctor. If you are pregnant, or think you may be pregnant, talk
to your doctor about using this medication during pregnancy. Birth control
pills, patches, implants, and injections may not work if taken with this
medication; discuss birth control with your doctor. This medication may lower
your folic acid levels, increasing the risk of spinal cord defects. Consult your
doctor to make sure you are taking enough folic acid. Prenatal care should
include tests for spinal cord defects. Small amounts of this drug pass into
breast milk. Consult your doctor before breastfeeding. Withdrawal symptoms may
occur if you suddenly stop taking this medication.

ADDITIONAL INFORMATION

Our Mebaral (mephobarbital) Side Effects Drug Center provides a comprehensive
view of available drug information on the potential side effects when taking
this medication.


FDA DRUG INFORMATION

 * Drug Description
 * Indications & Dosage
 * Side Effects
 * Drug Interactions
 * Warnings
 * Precautions
 * Overdose & Contraindications
 * Clinical Pharmacology
 * Medication Guide


DESCRIPTION FOR MEBARAL

Mephobarbital, 5-Ethyl-1-methyl-5-phenylbarbituric acid, is a babiturate with
sedative, hypnotic, and anticonvulsant properties. It occurs as a white, nearly
odorless, tasteless powder and is slightly soluble in water and in alcohol.

MEBARAL (mephobarbital) is available as tablets for oral administration. The
structural formula is:







Inactive Ingredients: Lactose, Starch, Stearic Acid, Talc.




USES FOR MEBARAL

MEBARAL (mephobarbital) is indicated for use as a sedative for the relief of
anxiety, tension, and apprehension, and as an anticonvulsant for the treatment
of grand mal and petit mal epilepsy.


DOSAGE FOR MEBARAL

Epilepsy: Average dose for adults: 400 mg to 600 mg (6 grains to 9 grains)
daily; children under 5 years: 16 mg to 32 mg (1/4 grain to ½ grain) three or
four times daily; children over 5 years: 32 mg to 64 mg (½ grain to 1 grain)
three or four times daily. MEBARAL (mephobarbital) is best taken at bedtime if
seizures generally occur at night, and during the day if attacks are diurnal.

Treatment should be started with a small dose which is gradually increased over
four or five days until the optimum dosage is determined. If the patient has
been taking some other antiepileptic drug, it should be tapered off as the doses
of MEBARAL (mephobarbital) are increased, to guard against the temporary marked
attacks that may occur when any treatment for epilepsy is changed abruptly.
Similarly, when the dose is lowered to a maintenance level or to be
discontinued, the amount should be reduced gradually over four or five days.

Special Patient Population: Dosage should be reduced in the elderly or
debilitated because these patients may be more sensitive to barbiturates. Dosage
should be reduced for patients with impaired renal function or hepatic disease.

Combination with Other Drugs: MEBARAL (mephobarbital) may be used in combination
with phenobarbital, either in the form of alternating courses or concurrently.
When the two drugs are used at the same time, the dose should be about one-half
the amount of each used alone. The average daily dose for an adult is from 50 mg
to 100 mg (3/4 grain to 1 ½ grains) of phenobarbital and from 200 mg to 300 mg
(3 grains to 4 ½ grains) of MEBARAL (mephobarbital) .

MEBARAL (mephobarbital) may also be used with phenytoin sodium; in some cases,
combined therapy appears to give better results than either agent used alone,
since phenytoin sodium is particularly effective for the psychomotor types of
seizure but relatively ineffective for petit mal. When the drugs are employed
concurrently, a reduced dose of phenytoin sodium is advisable, but the full dose
of MEBARAL (mephobarbital) may be given. Satisfactory results have been obtained
with an average daily dose of 230 mg (3 ½ grains) of phenytoin sodium plus about
600 mg (9 grains) of MEBARAL (mephobarbital) .

Sedation: Adults: 32 mg to 100 mg (½ grain to 1 ½ grains)–optimum dose, 50 mg
(3/4 grain)–three to four times daily. Children: 16 mg to 32 mg (1/4 grain to ½
grain) three to four times daily.


HOW SUPPLIED

Tablets—white, round, convex and the 32 mg and 50 mg tablets are scored.

32 mg (½ grain), bottles of 250 (NDC 67386-801-02).

50 mg (3/4 grain), bottles of 250 (NDC 67386-802-02).

100 mg (1 ½ grains), bottles of 250 (NDC 67386-803-02).

Store at room temperature up to 25° C (77° F).

Distributed by : OVATION, Pharmaceuticals, Inc., Deerfield, I 60015, USA.
Revised July 2003. FDA revision date: n/a


SIDE EFFECTS FOR MEBARAL

The following adverse reactions and their incidence were compiled from
surveillance of thousands of hospitalized patients. Because such patients may be
less aware of certain of the milder adverse effects of barbiturates, the
incidence of these reactions may be somewhat higher in fully ambulatory
patients.

More than 1 in 100 Patients. The most common adverse reactions estimated to
occur at a rate of 1 to 3 patients per 100 is:

Nervous System:Somnolence.

Less than 1 in 100 Patients. Adverse reactions estimated to occur at a rate of
less than 1 in 100 patients listed below, grouped by organ system, and by
decreasing order of occurrence are:

Nervous System: Agitation, confusion, hyperkinesia, ataxia, CNS depression,
nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia,
anxiety, dizziness, thinking abnormality.

Respiratory System: Hypoventilation, apnea.

Cardiovascular System: Bradycardia, hypotension, syncope.

Digestive System: Nausea, vomiting, constipation.

Other Reported Reactions: Headache, hypersensitivity reactions (angioedema, skin
rashes, exfoliative dermatitis), fever, liver damage, megaloblastic anemia
following chronic phenobarbital use.

DRUG ABUSE AND DEPENDENCE

Mephobarbital is a controlled substance in Narcotic Schedule IV. Barbiturates
may be habit forming. Tolerance, psychological dependence, and physical
dependence may occur especially following prolonged use of high doses of
barbiturates. As tolerance to barbiturates develops, the amount needed to
maintain the same level of intoxication increases; tolerance to a fatal dosage,
however, does not increase more than two-fold. As this occurs, the margin
between an intoxicating dosage and fatal dosage becomes smaller.

Symptoms of acute intoxication with barbiturates include unsteady gait, slurred
speech, and sustained nystagmus. Mental signs of chronic intoxication include
confusion, poor judgment, irritability, insomnia, and somatic complaints.

Symptoms of barbiturate dependence are similar to those of chronic alcoholism.
If an individual appears to be intoxicated with alcohol to a degree that is
radically disproportionate to the amount of alcohol in his or her blood the use
of barbiturates should be suspected. The lethal dose of a barbiturate is far
less if alcohol is also ingested.

The symptoms of barbiturate withdrawal can be severe and may cause death. Minor
withdrawal symptoms may appear 8 to 12 hours after the last dose of a
barbiturate. These symptoms usually appear in the following order: anxiety,
muscle twitching, tremor of hands and fingers, progressive weakness, dizziness,
distortion in visual perception, nausea, vomiting, insomnia, and orthostatic
hypotension. Major withdrawal symptoms (convulsions and delirium) may occur
within 16 hours and last up to 5 days after abrupt cessation of these drugs.
Intensity of withdrawal symptoms gradually declines over a period of
approximately 15 days. Individuals susceptible to a barbiturate abuse and
dependence include alcoholics and opiate abusers, as well as other
sedative-hypnotic and amphetamine abusers.

Drug dependence to barbiturates arises from repeated administration of a
barbiturate or agent with barbiturate-like effect on a continuous basis,
generally in amounts exceeding therapeutic dose levels. The characteristics of
drug dependence to barbiturates include: (a) a strong desire or need to continue
taking the drug; (b) a tendency to increase the dose; (c) a psychic dependence
on the effects of the drug related to subjective and individual appreciation of
those effects; and (d) a physical dependence on the effects of the drug
requiring its presence for maintenance of homeostasis and resulting in a
definite, characteristic, and self-limited abstinence syndrome when the drug is
withdrawn.

Treatment of barbiturate dependence consists of cautious and gradual withdrawal
of the drug. Barbiturate-dependent patients can be withdrawn by using a number
of different withdrawal regimens. In all cases withdrawal takes an extended
period of time. One method involves substituting a 30 mg dose of phenobarbital
for each 100 mg to 200 mg dose of barbiturate that the patient has been taking.
The total daily amount of phenobarbital is then administered in 3 to 4 divided
doses, not to exceed 600 mg daily. Should signs of withdrawal occur on the first
day of treatment, a loading dose of 100 mg to 200 mg of phenobarbital may be
administered IM in addition to the oral dose. After stabilization on
phenobarbital, the total daily dose is decreased by 30 mg a day as long as
withdrawal is proceeding smoothly. A modification of this regimen involves
initiating treatment at the patient's regular dosage level and decreasing the
daily dosage by 10% if tolerated by the patient.

Infants physically dependent on barbiturates may be given phenobarbital 3
mg/kg/day to 10 mg/kg/day. After withdrawal symptoms (hyperactivity, disturbed
sleep, tremors, hyperreflexia) are relieved, the dosage of phenobarbital should
be gradually decreased and completely withdrawn over a 2-week period.


DRUG INTERACTIONS FOR MEBARAL

Most reports of clinically significant drug interactions occurring with the
barbiturates have involved phenobarbital. However, the application of these data
to other barbiturates appears valid and warrants serial blood level
determinations of the relevant drugs when there are multiple therapies.

 1. Anticoagulants. Phenobarbital lowers the plasma levels of dicumarol (name
    previously used: bishydroxycoumarin) and causes a decrease in anticoagulant
    activity as measured by the prothrombin time. Barbiturates can induce
    hepatic microsomal enzymes resulting in increased metabolism and decreased
    anticoagulant response of oral anticoagulants (e.g., warfarin,
    acenocoumarol, dicumarol, and phenprocoumon). Patients stabilized on
    anticoagulant therapy may require dosage adjustments if barbiturates are
    added to or withdrawn from their dosage regimen.
 2. Corticosteroids. Barbiturates appear to enhance the metabolism of exogenous
    corticosteroids probably through the induction of hepatic microsomal
    enzymes. Patients stabilized on corticosteroid therapy may require dosage
    adjustments if barbiturates are added to or withdrawn from their dosage
    regimen.
 3. Griseofulvin. Phenobarbital appears to interfere with the absorption of
    orally administered griseofulvin, thus decreasing its blood level. The
    effect of the resultant decreased blood levels of griseofulvin on
    therapeutic response has not been established. However, it would be
    preferable to avoid concomitant administration of these drugs.
 4. Doxycycline. Phenobarbital has been shown to shorten the half-life of
    doxycycline for as long as 2 weeks after barbiturate therapy is
    discontinued. This mechanism is probably through the induction of hepatic
    microsomal enzymes that metabolize the antibiotic. If phenobarbital and
    doxycycline are administered concurrently, the clinical response to
    doxycycline should be monitored closely.
 5. Phenytoin, Sodium Valproate, Valproic Acid. The effect of barbiturates on
    the metabolism of phenytoin appears to be variable. Some investigators
    report an accelerating effect, while others report no effect. Because the
    effect of barbiturates on the metabolism of phenytoin is not predictable,
    phenytoin and barbiturate blood levels should be monitored more frequently
    if these drugs are given concurrently. Sodium valproate and valproic acid
    appear to decrease barbiturate metabolism; therefore, barbiturate blood
    levels should be monitored and appropriate dosage adjustments made as
    indicated.
 6. Central Nervous System Depressants. The concomitant use of other central
    nervous system depressants, including other sedatives or hypnotics,
    antihistamines, tranquilizers, or alcohol, may produce additive depressant
    effects.
 7. Monoamine Oxidase Inhibitors (MAOI). MAOI prolong the effects of
    barbiturates probably because metabolism of the barbiturate is inhibited.
 8. Estradiol, Estrone, Progesterone, and other Steroidal Hormones. Pretreatment
    with or concurrent administration of phenobarbital may decrease the effect
    of estradiol by increasing its metabolism. There have been reports of
    patients treated with antiepileptic drugs (e.g., phenobarbital) who become
    pregnant while taking oral contraceptives. An alternate contraceptive method
    might be suggested to women taking phenobarbital.


WARNINGS FOR MEBARAL

HABIT FORMING

Barbiturates may be habit forming. Tolerance, psychological, and physical
dependence may occur with continued use. (See Drug abuse and Dependence and
CLINICAL PHARMACOLOGY.) Patients who have psychological dependence on
barbiturates may increase the dosage or decrease the dosage interval without
consulting a physician and may subsequently develop a physical dependence on
barbiturates. To minimize the possibility of overdosage or the development of
dependence, the prescribing and dispensing of sedative-hypnotic barbiturates
should be limited to the amount required for the interval until the next
appointment. Abrupt cessation after prolonged use in the dependent person may
result in withdrawal symptoms, including delirium, convulsions, and possibly
death. Barbiturates should be withdrawn gradually from any patient known to be
taking excessive dosage over long periods of time. (See Drug abuse and
Dependence.)

ACUTE OR CHRONIC PAIN

Caution should be exercised when barbiturates are administered to patients with
acute or chronic pain, because paradoxical excitement could be induced or
important symptoms could be masked. However, the use of barbiturates as
sedatives in the postoperative surgical period and as adjuncts to cancer
chemotherapy is well established.

USE IN PREGNANCY

Barbiturates can cause fetal damage when administered to a pregnant woman.
Retrospective, case-controlled studies have suggested a connection between the
maternal consumption of barbiturates and a higher than expected incidence of
fetal abnormalities. Following oral or parenteral administration, barbiturates
readily cross the placental barrier and are distributed throughout fetal tissues
with highest concentrations found in the placenta, fetal liver, and brain. Fetal
blood levels approach maternal blood levels following parenteral administration.

Withdrawal symptoms occur in infants born to mothers who receive barbiturates
throughout the last trimester of pregnancy. (See Drug abuse and Dependence.) If
this drug is used during pregnancy, or if the patient becomes pregnant while
taking this drug, the patient should be apprised of the potential hazard to the
fetus.

SYNERGISTIC EFFECTS

The concomitant use of alcohol or other CNS depressants may produce additive CNS
depressant effects.


PRECAUTIONS FOR MEBARAL

GENERAL

Barbiturates may be habit forming. Tolerance and psychological and physical
dependence may occur with continuing use. (See Drug abuse and Dependence.)
Barbiturates should be administered with caution, if at all, to patients who are
mentally depressed, have suicidal tendencies, or a history of drug abuse.

Elderly or debilitated patients may react to barbiturates with marked
excitement, depression, and confusion. In some persons, barbiturates repeatedly
produce excitement rather than depression.

In patients with hepatic damage, barbiturates should be administered with
caution and initially in reduced doses. Barbiturates should not be administered
to patients showing the premonitory signs of hepatic coma.

Status epilepticus may result from the abrupt discontinuation of MEBARAL
(mephobarbital) , even when administered in small daily doses in the treatment
of epilepsy.

Caution and careful adjustment of dosage are required when MEBARAL
(mephobarbital) is used in patients with impaired renal, cardiac or respiratory
function, and in patients with myasthenia gravis and myxedema. The least
quantity feasible should be prescribed or dispensed at any one time in order to
minimize the possibility of acute or chronic overdosage.

Vitamin D Deficiency: MEBARAL (mephobarbital) may increase vitamin D
requirements, possibly by increasing vitamin D metabolism via enzyme induction.
Rarely, rickets and osteomalacia have been reported following prolonged use of
barbiturates.

Vitamin K: Bleeding in the early neonatal period due to coagulation defects may
follow exposure to anticonvulsant drugs in utero; therefore, vitamin K should be
given to the mother before delivery or to the child at birth.

LABORATORY TESTS

Prolonged therapy with barbiturates should be accompanied by periodic laboratory
evaluation of organ systems, including hematopoietic, renal, and hepatic
systems. (See PRECAUTIONS [General] and ADVERSE REACTIONS.)

CARCINOGENESIS

ANIMAL DATA

Phenobarbital sodium is carcinogenic in mice and rats after lifetime
administration. In mice, it produced benign and malignant liver cell tumors. In
rats, benign liver cell tumors were observed very late in life. Phenobarbital is
the major metabolite of MEBARAL (mephobarbital) .

HUMAN DATA

In a 29-year epidemiological study of 9,136 patients who were treated on an
anticonvulsant protocol which included phenobarbital, results indicated a higher
than normal incidence of hepatic carcinoma. Previously, some of these patients
were treated with thorotrast, a drug which is known to produce hepatic
carcinomas. Thus, this study did not provide sufficient evidence that
Phenobarbital sodium is carcinogenic in humans. Phenobarbital is the major
metabolite of MEBARAL (mephobarbital) .

A retrospective study of 84 children with brain tumors matched to 73 normal
controls and 78 cancer controls (malignant disease other than brain tumors)
suggested an association between exposure to barbiturates prenatally and an
increased incidence of brain tumors.

PREGNANCY

TERATOGENIC EFFECTS

Pregnancy Category D-See WARNINGS-Use in Pregnancy.

NONTERATOGENIC EFFECTS

Reports of infants suffering from long-term barbiturate exposure in utero
included the acute withdrawal syndrome of seizures and hyperirritability from
birth to a delayed onset of up to 14 days. (See Drug abuse and Dependence.)

LABOR AND DELIVERY

Hypnotic doses of these barbiturates do not appear to significantly impair
uterine activity during labor. Full anesthetic doses of barbiturates decrease
the force and frequency of uterine contractions. Administration of
sedative-hypnotic barbiturates to the mother during labor may result in
respiratory depression in the newborn. Premature infants are particularly
susceptible to the depressant effects of barbiturates. If barbiturates are used
during labor and delivery, resuscitation equipment should be available.

Data are currently not available to evaluate the effect of these barbiturates
when forceps delivery or other intervention is necessary. Also, data are not
available to determine the effect of these barbiturates on the later growth,
development, and functional maturation of the child.

NURSING MOTHERS

Caution should be exercised when a barbiturate is administered to a nursing
woman since small amounts of barbiturates are excreted in the milk.


OVERDOSE INFORMATION FOR MEBARAL

The toxic dose of barbiturates varies considerably. In general, an oral dose of
1 g of most barbiturates produces serious poisoning in an adult. Death commonly
occurs after 2 g to 10 g of ingested barbiturate. Barbiturate intoxication may
be confused with alcoholism, bromide intoxication, and with various neurological
disorders.

Acute overdosage with barbiturates is manifested by CNS and respiratory
depression which may progress to Cheyne-Stokes respiration, areflexia,
constriction of the pupils to a slight degree (though in severe poisoning they
may show paralytic dilation), oliguria, tachycardia, hypotension, lowered body
temperature, and coma. Typical shock syndrome (apnea, circulatory collapse,
respiratory arrest, and death) may occur.

In extreme overdose, all electrical activity in the brain may cease, in which
case a “flat” EEG normally equated with clinical death cannot be accepted. This
effect is fully reversible unless hypoxic damage occurs. Consideration should be
given to the possibility of barbiturate intoxication even in situations that
appear to involve trauma.

Complications such as pneumonia, pulmonary edema, cardiac arrhythmias,
congestive heart failure, and renal failure may occur. Uremia may increase CNS
sensitivity to barbiturates if renal function is impaired. Differential
diagnosis should include hypoglycemia, head trauma, cerebrovascular accidents,
convulsive states, and diabetic coma.

Treatment of overdosage is mainly supportive and consists of the following:

 1.  Maintenance of an adequate airway, with assisted respiration and oxygen
     administration as necessary.
 2.  Monitoring of vital signs and fluid balance.
 3.  If the patient is conscious and has not lost the gag reflex, emesis may be
     induced with ipecac. Care should be taken to prevent pulmonary aspiration
     of vomitus. After completion of vomiting, 30 g activated charcoal in a
     glass of water may be administered.
 4.  If emesis is contraindicated, gastric lavage may be performed with a cuffed
     endotracheal tube in place with the patient in the face down position.
     Activated charcoal may be left in the emptied stomach and a saline
     cathartic administered.
 5.  Fluid therapy and other standard treatment for shock, if needed.
 6.  If renal function is normal, forced diuresis may aid in the elimination of
     the barbiturate. Alkalinization of the urine increases renal excretion of
     some barbiturates, including mephobarbital (which is metabolized to
     phenobarbital).
 7.  Although not recommended as a routine procedure, hemodialysis may be used
     in severe barbiturate intoxications or if the patient is anuric or in
     shock.
 8.  Patient should be rolled from side to side every 30 minutes.
 9.  Antibiotics should be given if pneumonia is suspected.
 10. Appropriate nursing care to prevent hypostatic pneumonia, decubiti
     aspiration, and other complications of patients with altered states of
     consciousness.


CONTRAINDICATIONS FOR MEBARAL

Hypersensitivity to any barbiturate. Manifest or latent porphyria.


CLINICAL PHARMACOLOGY FOR MEBARAL

Barbiturates are capable of producing all levels of CNS mood alteration from
excitation to mild sedation, to hypnosis, and deep coma. Overdosage can produce
death. In high enough therapeutic doses, barbiturates induce anesthesia.

Barbiturates depress the sensory cortex, decrease motor activity, alter
cerebellar function, and produce drowsiness, sedation, and hypnosis.

Barbiturates are respiratory depressants. The degree of respiratory depression
is dependent upon dose. With hypnotic doses, respiratory depression produced by
barbiturates is similar to that which occurs during physiologic sleep with
slight decrease in blood pressure and heart rate.

Studies in laboratory animals have shown that barbiturates cause reduction in
the tone and contractility of the uterus, ureters, and urinary bladder. However,
concentrations of the drugs required to produce this effect in humans are not
reached with sedative-hypnotic doses.

Barbiturates do not impair normal hepatic function, but have been shown to
induce liver microsomal enzymes, thus increasing and/or altering the metabolism
of barbiturates and other drugs. (See PRECAUTIONS - DRUG INTERACTIONS.)

MEBARAL (mephobarbital) exerts a strong sedative and anticonvulsant action but
has a relatively mild hypnotic effect. It reduces the incidence of epileptic
seizures in grand mal and petit mal. MEBARAL (mephobarbital) usually causes
little or no drowsiness or lassitude. Hence, when it is used as a sedative or
anticonvulsant, patients usually become more calm, more cheerful, and better
adjusted to their surroundings without clouding of mental faculties. MEBARAL
(mephobarbital) is reported to produce less sedation than does phenobarbital.

Barbiturates are weak acids that are absorbed and rapidly distributed to all
tissues and fluids with high concentrations in the brain, liver, and kidneys.
Lipid solubility of the barbiturates is the dominant factor in their
distribution within the body. Barbiturates are bound to plasma and tissue
proteins to a varying degree with the degree of binding increasing directly as a
function of lipid solubility.

Approximately 50% of an oral dose of mephobarbital is absorbed from the
gastrointestinal tract. Therapeutic plasma concentrations for mephobarbital have
not been established nor has the half-life been determined. Following oral
administration, the onset of action of the drug is 30 to 60 minutes and the
duration of action is 10 to 16 hours. The primary route of mephobarbital
metabolism is N-demethylation by the microsomal enzymes of the liver to form
phenobarbital. Phenobarbital may be excreted in the urine unchanged or further
metabolized to p-hydroxyphenobarbital and excreted in the urine as glucuronide
or sulfate conjugates. About 75% of a single oral dose of mephobarbital is
converted to phenobarbital in 24 hours.

Therefore, chronic administration of mephobarbital may lead to an accumulation
of phenobarbital (not mephobarbital) in plasma. It has not been determined
whether mephobarbital or phenobarbital is the active agent during long-time
mephobarbital therapy.


PATIENT INFORMATION FOR MEBARAL

Practitioners should give the following information and instructions to patients
receiving barbiturates.

 1. The use of barbiturates carries with it an associated risk of psychological
    and/or physical dependence. The patient should be warned against increasing
    the dose of the drug without consulting a physician.
 2. Barbiturates may impair mental and/or physical abilities required for the
    performance of potentially hazardous tasks (e.g., driving, operating
    machinery, etc.).
 3. Alcohol should not be consumed while taking barbiturates. Concurrent use of
    the barbiturates with other CNS depressants (e.g., alcohol, narcotics,
    tranquilizers, and antihistamines) may result in additional CNS depressant
    effects.


FROM

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These cookies do not store any personally identifiable information.

TARGETING COOKIES

Targeting Cookies

These cookies may be set through our site by our advertising partners. They may
be used by those companies to build a profile of your interests and show you
relevant adverts on other sites. They do not store directly personal
information, but are based on uniquely identifying your browser and internet
device. If you do not allow these cookies, you will experience less targeted
advertising.

PERFORMANCE COOKIES

Performance Cookies

These cookies allow us to count visits and traffic sources so we can measure and
improve the performance of our site. They help us to know which pages are the
most and least popular and see how visitors move around the site. All
information these cookies collect is aggregated and therefore anonymous. If you
do not allow these cookies we will not know when you have visited our site, and
will not be able to monitor its performance.

FUNCTIONAL COOKIES

Functional Cookies

These cookies enable the website to provide enhanced functionality and
personalisation. They may be set by us or by third party providers whose
services we have added to our pages. If you do not allow these cookies then some
or all of these services may not function properly.

STORE AND/OR ACCESS INFORMATION ON A DEVICE 51 PARTNERS CAN USE THIS PURPOSE

Store and/or access information on a device

Cookies, device or similar online identifiers (e.g. login-based identifiers,
randomly assigned identifiers, network based identifiers) together with other
information (e.g. browser type and information, language, screen size, supported
technologies etc.) can be stored or read on your device to recognise it each
time it connects to an app or to a website, for one or several of the purposes
presented here.

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PERSONALISED ADVERTISING AND CONTENT, ADVERTISING AND CONTENT MEASUREMENT,
AUDIENCE RESEARCH AND SERVICES DEVELOPMENT 56 PARTNERS CAN USE THIS PURPOSE

Personalised advertising and content, advertising and content measurement,
audience research and services development

 * USE LIMITED DATA TO SELECT ADVERTISING 46 PARTNERS CAN USE THIS PURPOSE
   
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   Advertising presented to you on this service can be based on limited data,
   such as the website or app you are using, your non-precise location, your
   device type or which content you are (or have been) interacting with (for
   example, to limit the number of times an ad is presented to you).
   
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 * CREATE PROFILES FOR PERSONALISED ADVERTISING 39 PARTNERS CAN USE THIS PURPOSE
   
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   Information about your activity on this service (such as forms you submit,
   content you look at) can be stored and combined with other information about
   you (for example, information from your previous activity on this service and
   other websites or apps) or similar users. This is then used to build or
   improve a profile about you (that might include possible interests and
   personal aspects). Your profile can be used (also later) to present
   advertising that appears more relevant based on your possible interests by
   this and other entities.
   
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 * USE PROFILES TO SELECT PERSONALISED ADVERTISING 39 PARTNERS CAN USE THIS
   PURPOSE
   
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   Advertising presented to you on this service can be based on your advertising
   profiles, which can reflect your activity on this service or other websites
   or apps (like the forms you submit, content you look at), possible interests
   and personal aspects.
   
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 * CREATE PROFILES TO PERSONALISE CONTENT 14 PARTNERS CAN USE THIS PURPOSE
   
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   Information about your activity on this service (for instance, forms you
   submit, non-advertising content you look at) can be stored and combined with
   other information about you (such as your previous activity on this service
   or other websites or apps) or similar users. This is then used to build or
   improve a profile about you (which might for example include possible
   interests and personal aspects). Your profile can be used (also later) to
   present content that appears more relevant based on your possible interests,
   such as by adapting the order in which content is shown to you, so that it is
   even easier for you to find content that matches your interests.
   
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 * USE PROFILES TO SELECT PERSONALISED CONTENT 12 PARTNERS CAN USE THIS PURPOSE
   
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   Content presented to you on this service can be based on your content
   personalisation profiles, which can reflect your activity on this or other
   services (for instance, the forms you submit, content you look at), possible
   interests and personal aspects. This can for example be used to adapt the
   order in which content is shown to you, so that it is even easier for you to
   find (non-advertising) content that matches your interests.
   
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 * MEASURE ADVERTISING PERFORMANCE 52 PARTNERS CAN USE THIS PURPOSE
   
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   Information regarding which advertising is presented to you and how you
   interact with it can be used to determine how well an advert has worked for
   you or other users and whether the goals of the advertising were reached. For
   instance, whether you saw an ad, whether you clicked on it, whether it led
   you to buy a product or visit a website, etc. This is very helpful to
   understand the relevance of advertising campaigns.
   
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 * MEASURE CONTENT PERFORMANCE 16 PARTNERS CAN USE THIS PURPOSE
   
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   Information regarding which content is presented to you and how you interact
   with it can be used to determine whether the (non-advertising) content e.g.
   reached its intended audience and matched your interests. For instance,
   whether you read an article, watch a video, listen to a podcast or look at a
   product description, how long you spent on this service and the web pages you
   visit etc. This is very helpful to understand the relevance of
   (non-advertising) content that is shown to you.
   
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 * UNDERSTAND AUDIENCES THROUGH STATISTICS OR COMBINATIONS OF DATA FROM
   DIFFERENT SOURCES 33 PARTNERS CAN USE THIS PURPOSE
   
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   Reports can be generated based on the combination of data sets (like user
   profiles, statistics, market research, analytics data) regarding your
   interactions and those of other users with advertising or (non-advertising)
   content to identify common characteristics (for instance, to determine which
   target audiences are more receptive to an ad campaign or to certain
   contents).
   
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 * DEVELOP AND IMPROVE SERVICES 48 PARTNERS CAN USE THIS PURPOSE
   
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   Information about your activity on this service, such as your interaction
   with ads or content, can be very helpful to improve products and services and
   to build new products and services based on user interactions, the type of
   audience, etc. This specific purpose does not include the development or
   improvement of user profiles and identifiers.
   
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   Object to Legitimate Interests Remove Objection

 * USE LIMITED DATA TO SELECT CONTENT 6 PARTNERS CAN USE THIS PURPOSE
   
   Switch Label
   
   Content presented to you on this service can be based on limited data, such
   as the website or app you are using, your non-precise location, your device
   type, or which content you are (or have been) interacting with (for example,
   to limit the number of times a video or an article is presented to you).
   
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   Object to Legitimate Interests Remove Objection

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USE PRECISE GEOLOCATION DATA 15 PARTNERS CAN USE THIS PURPOSE

Use precise geolocation data

With your acceptance, your precise location (within a radius of less than 500
metres) may be used in support of the purposes explained in this notice.

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ACTIVELY SCAN DEVICE CHARACTERISTICS FOR IDENTIFICATION 3 PARTNERS CAN USE THIS
PURPOSE

Actively scan device characteristics for identification

With your acceptance, certain characteristics specific to your device might be
requested and used to distinguish it from other devices (such as the installed
fonts or plugins, the resolution of your screen) in support of the purposes
explained in this notice.

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ENSURE SECURITY, PREVENT AND DETECT FRAUD, AND FIX ERRORS 48 PARTNERS CAN USE
THIS PURPOSE

Always Active

Your data can be used to monitor for and prevent unusual and possibly fraudulent
activity (for example, regarding advertising, ad clicks by bots), and ensure
systems and processes work properly and securely. It can also be used to correct
any problems you, the publisher or the advertiser may encounter in the delivery
of content and ads and in your interaction with them.

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DELIVER AND PRESENT ADVERTISING AND CONTENT 41 PARTNERS CAN USE THIS PURPOSE

Always Active

Certain information (like an IP address or device capabilities) is used to
ensure the technical compatibility of the content or advertising, and to
facilitate the transmission of the content or ad to your device.

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MATCH AND COMBINE DATA FROM OTHER DATA SOURCES 39 PARTNERS CAN USE THIS PURPOSE

Always Active

Information about your activity on this service may be matched and combined with
other information relating to you and originating from various sources (for
instance your activity on a separate online service, your use of a loyalty card
in-store, or your answers to a survey), in support of the purposes explained in
this notice.

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LINK DIFFERENT DEVICES 35 PARTNERS CAN USE THIS PURPOSE

Always Active

In support of the purposes explained in this notice, your device might be
considered as likely linked to other devices that belong to you or your
household (for instance because you are logged in to the same service on both
your phone and your computer, or because you may use the same Internet
connection on both devices).

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IDENTIFY DEVICES BASED ON INFORMATION TRANSMITTED AUTOMATICALLY 36 PARTNERS CAN
USE THIS PURPOSE

Always Active

Your device might be distinguished from other devices based on information it
automatically sends when accessing the Internet (for instance, the IP address of
your Internet connection or the type of browser you are using) in support of the
purposes exposed in this notice.

List of IAB Vendors‎
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