Barbiturates (Systemic)

This monograph includes information on the following:

1) Amobarbital
2) Aprobarbital  
3) Butabarbital
4) Mephobarbital
5) Metharbital  * 
6) Pentobarbital
7) Phenobarbital
8) Secobarbital
9) Secobarbital and Amobarbital

VA CLASSIFICATION
Amobarbital Oral
Primary: CN301

Amobarbital Parenteral
Primary: CN301
Secondary: CN400

Aprobarbital Oral
Primary: CN301

Butabarbital Oral
Primary: CN301

Mephobarbital Oral
Primary: CN400

Metharbital Oral
Primary: CN400

Pentobarbital Oral
Primary: CN301

Pentobarbital Parenteral
Primary: CN301
Secondary: CN400

Phenobarbital Oral
Primary: CN301
Secondary: CN400; GA900

Phenobarbital Parenteral
Primary: CN301
Secondary: CN400; GA900

Secobarbital Oral
Primary: CN301

Secobarbital Parenteral
Primary: CN301
Secondary: CN400


Note: Controlled substance classification—

Note: Controlled substances in the U.S. and Canada as follows {119}9 {119}8 {119}7 {119}6 {119}5 {119}4 {119}3:



Drug
U.S.
Canada
Amobarbital
II
C
Aprobarbital
III
 
Butabarbital
III
C
Mephobarbital
IV
C
Pentobarbital
Oral
II
C
Parenteral
II
C
Rectal
III
C
Phenobarbital
IV
C
Secobarbital
Oral
II
C
Parenteral
II
 
Secobarbital and
Amobarbital
II
C
Commonly used brand name(s): Alurate2; Amytal1; Ancalixir7; Barbita7; Busodium3; Butalan3; Butisol3; Gemonil5; Luminal7; Mebaral4; Nembutal6; Nova Rectal6; Novopentobarb6; Novosecobarb8; Sarisol No. 23; Seconal8; Solfoton7; Tuinal9.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Sedative-hypnotic—Amobarbital; Aprobarbital; Butabarbital; Pentobarbital; Phenobarbital (parenteral only); Secobarbital;

Anticonvulsant—Amobarbital (parenteral only); Mephobarbital; Metharbital; Pentobarbital (parenteral only); Phenobarbital; Secobarbital (parenteral only);

Antihyperbilirubinemic—Phenobarbital;

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Anesthesia, adjunct—Amobarbital, butabarbital, pentobarbital, phenobarbital (parenteral), and secobarbital are indicated for use as preoperative medication to help reduce anxiety and facilitate induction of anesthesia {119}2 {119}1 {119}0 {167}9 {167}8 {167}7 {167}6 {167}5 {167}4 {167}3 {167}2 {167}1 {167}0.

Narcoanalysis—Amobarbital (parenteral) may be indicated in narcoanalysis {04}9 {04}8 {04}7.

Epilepsy, tonic-clonic seizure pattern (treatment) or
Epilepsy, simple partial seizure pattern (treatment)—Phenobarbital {04}6 {04}5 {04}4, a long-acting barbiturate, is indicated as long-term anticonvulsant therapy for the treatment of generalized tonic-clonic and simple partial (cortical focal) seizures; mephobarbital {04}3 {04}2 {04}1 and metharbital, also long-acting barbiturates, may be indicated as alternatives to phenobarbital {04}0 {55}9 {55}8 {55}7 {55}6.

Convulsions (treatment)
Seizures (prophylaxis and treatment)
Status epilepticus (treatment) or
Tetanus (treatment adjunct)—Parenteral barbiturates {55}5 {55}4, especially phenobarbital, are indicated in the emergency treatment of certain acute convulsive episodes such as those associated with status epilepticus, eclampsia, meningitis, and toxic reactions to strychnine. They are also indicated as adjunctive treatment for acute convulsive episodes associated with tetanus. {55}3 {55}2 {55}1 {55}0 {113}9 {113}8 {113}7 {113}6 {113}5
—Phenobarbital is used in the prophylaxis and treatment of febrile seizures{113}4{113}3{113}2 .1

[Hyperbilirubinemia (prophylaxis and treatment)]1—Phenobarbital (oral and parenteral) is used in the prevention and treatment of hyperbilirubinemia in neonates. It is used also to lower bilirubin concentrations in patients with congenital nonhemolytic unconjugated hyperbilirubinemia or chronic intrahepatic cholestasis. {113}1

[Ischemia, cerebral (treatment)]1or
[Hypertension, cerebral (treatment)]1—Pentobarbital (parenteral) is used for induction of coma to protect the brain from various states, including ischemia and increased intracranial pressure that follow stroke and head trauma; however, this use is controversial and further studies are needed.

—Amobarbital, aprobarbital, butabarbital, pentobarbital, phenobarbital, secobarbital, and secobarbital and amobarbital have been used for the short-term treatment of insomnia; however, they generally have been replaced by benzodiazepines. If barbiturates are used, they are not recommended for long-term use since they appear to lose their effectiveness in sleep induction and maintenance after 2 weeks or less. {113}0 {117}9 {117}8 {117}7 {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8 {119}7 {119}6 {119}5 {119}4 {119}3 {119}2 {119}1 {119}0 {04}9 {04}8 {04}7 {04}6 {04}5 {04}4 {04}3 {04}2 {04}1 {04}0

—Amobarbital, aprobarbital, butabarbital, mephobarbital, pentobarbital, phenobarbital, and secobarbital have also been used for routine sedation to relieve anxiety, tension, and apprehension {13}9 {13}8 {13}7 {13}6 {13}5 {13}4 {13}3 {13}2; however, barbiturates generally have been replaced by benzodiazepines for daytime sedation {13}1 {13}0 {113}9 {113}8 {113}7 {113}6 {113}5 {113}4.

Unaccepted
Amobarbital (parenteral) has been used as a diagnostic aid in schizophrenia {113}3 but it generally has been replaced by other agents {113}2.

Amobarbital (parenteral) has also been used in the management of catatonic and negativistic reactions {113}1; however, phenothiazines generally are more appropriate therapy for catatonic reactions. It has also been used in the management of manic reactions, although benzodiazepines and lithium are usually preferred. {113}0

[Phenobarbital (oral and parenteral) has been used in the treatment of familial, senile, or essential action tremors; however, it generally has been replaced by other agents, such as benzodiazepines and beta-adrenergic blockers.]

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Table 1. Pharmacology/Pharmacokinetics



Drug
Protein
Binding *
(%)
Half-life (hr)
Onset of
Action
(min)
Duration
of Action
(hr)
Elimination/
% Excreted
Unchanged §
Range
Mean
Long-acting
      60 or longer
10–12
 
Mephobarbital #
  11–67
34
    Renal
Metharbital
          Renal/2%; 20%
excreted as
barbital
Phenobarbital
Low to
Moderate
(20–45)
53–118 **
79
    Renal/25–50%
Intermediate-acting
      45–60
6–8
 
Amobarbital
Moderate (61)
16–40
25
    Renal/<1%
Aprobarbital
Low (20)
14–34
24
    Renal/25–50%
Butabarbital
Low (26)
34–42
††
 
    Renal/<1%
Short-acting
      10–15
3–4
 
Pentobarbital
Moderate to
High (60–70)
15–50
‡‡
 
    Renal/<1%
Secobarbital
Moderate to
High (46–70)
15–40
28
    Renal/5%
* Bound to plasma and tissue proteins to a varying degree; binding increases proportionate to lipid solubility {97}9 {97}8 {97}7 {97}6 {97}5 {97}4 {97}3 {97}2 {97}1 {97}0 {98}9
 Following oral administration. Phenobarbital has the slowest, and secobarbital the fastest, onset of action {98}8 {98}7 {98}6 {98}5 {98}4 {98}3
 Following oral administration. Duration of action is related to the rate at which the barbiturates are redistributed throughout the body and is variable among individuals and in the same individual from time to time. Phenobarbital has the longest, and secobarbital the shortest, duration of action {98}2 {98}1 {98}0 {110}9 {110}8 {110}7 {110}6 {110}5 {110}4 {110}3 {110}2
§ Metabolic products are excreted in the urine and, less commonly, in the feces. Inactive metabolites are excreted as conjugates of glucuronic acid. {110}1 {110}0 {110}9 {110}8 {110}7 {110}6 {110}5 {110}4 {110}3 {110}2 {110}1 {110}0
Peritoneal dialysis and hemodialysis {16}9 remove phenobarbital from the body; serum phenobarbital concentrations should be determined during and after peritoneal dialysis and hemodialysis {16}8
# Activity due mostly to accumulation of phenobarbital
** Half-life is 60 to 180 hours in children (half-life 48 hours or less for newborns) {16}7 {16}6
†† One manufacturer states that the half-life of butabarbital is 100 hours {16}5 {16}4 {16}3 {16}2 {16}1 {16}0 {117}9
‡‡ Dose-dependent; the mean half-life of elimination is 50 and 22 hours following a 50- and 100-mg dose, respectively {117}8

Physicochemical characteristics:
Molecular weight—
    Amobarbital: 226.27
    Amobarbital sodium: 248.26
    Aprobarbital: 210.23
    Butabarbital sodium: 234.23
    Mephobarbital: 246.27
    Metharbital: 198.22
    Pentobarbital: 226.27
    Pentobarbital sodium: 248.26
    Phenobarbital: 232.24
    Phenobarbital sodium: 254.22
    Secobarbital sodium: 260.27

Mechanism of action/Effect:

Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma {117}7 {117}6 {117}5 {117}4 {117}3 {117}2 {117}1. In sufficiently high therapeutic doses, barbiturates induce anesthesia. Recent studies have suggested that the sedative-hypnotic and anticonvulsant effects of barbiturates may be related to their ability to enhance and/or mimic the inhibitory synaptic action of gamma-aminobutyric acid (GABA). {117}0 {118}9 {118}8 {118}7 {118}6 {118}5 {118}4 {118}3 {118}2


Sedative-hypnotic:

Barbiturates depress the sensory cortex, decrease motor activity, alter cerebral function, and produce drowsiness, sedation, and hypnosis {118}1 {118}0 {16}9. Although the mechanism of action has not been completely established, the barbiturates appear to have a particular effect {16}8 at the level of the thalamus where they inhibit ascending conduction in the reticular formation, thus interfering with the transmission of impulses to the cortex.

The mechanism of action of pentobarbital in protecting the brain from ischemia and intracranial pressure is not completely understood; however, it is related to pentobarbital's anesthetic action (produced by sufficiently high dosage) and possibly to the depression of neuronal activity and metabolism {16}7.



Anticonvulsant:

Barbiturates are believed to act by depressing monosynaptic and polysynaptic transmission in the CNS. They also increase the threshold for electrical stimulation of the motor cortex.



Antihyperbilirubinemic:

Phenobarbital lowers serum bilirubin concentrations probably by induction of glucuronyl transferase, the enzyme which conjugates bilirubin.



Other actions/effects:

Barbiturates have little analgesic action at subanesthetic doses and may increase reaction to painful stimuli {16}6 {16}5 {16}4 {16}3 {16}2 {16}1 {16}0 {167}9 {167}8 {167}7.

Although phenobarbital, mephobarbital, and metharbital are the only barbiturates effective as anticonvulsants in subhypnotic doses, all of the barbiturates exhibit anticonvulsant activity in anesthetic doses {167}6 {167}5 {167}4 {167}3 {167}2 {167}1 {167}0 {15}9.

Barbiturates are respiratory depressants; the degree of respiratory depression is dose-dependent {15}8 {15}7 {15}6 {15}5 {15}4 {15}3 {15}2 {15}1 {15}0 {119}9 {119}8 {119}7 {119}6 {119}5 {119}4 {119}3 {119}2 {119}1.

Barbiturates have been shown to reduce the rapid eye movement (REM) phase of sleep or dreaming stage. Also, Stages III and IV sleep (slow-wave sleep, SWS) are decreased. {119}0 {04}9 {04}8 {04}7 {04}6 {04}5 {04}4 {04}3 {04}2 {04}1 {04}0 {117}9 {117}8 {117}7

Animal studies have shown that barbiturates cause reduction in the tone and contractility of the uterus, ureters, and urinary bladder; however, concentrations required to produce this effect in humans are not attained with sedative-hypnotic doses {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8.

Barbiturates have been shown to induce liver microsomal enzymes, thereby increasing and altering the metabolism of {119}7 other medications or compounds {119}6 {119}5 {119}4 {119}3 {119}2 {119}1 {119}0 {15}9 {15}8 {15}7 {15}6 {15}5 {15}4 {15}3 {15}2 {15}1 {15}0 {117}9 {117}8.

Absorption:

Absorbed in varying degrees following oral, parenteral, or rectal administration {117}7 {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {119}9.

Barbiturate sodium salts are absorbed more rapidly than the free acids because of rapid dissolution {119}8 {119}7 {119}6 {119}5 {119}4 {119}3 {119}2 {119}1 {119}0 {16}9.

The rate of absorption is increased if barbiturates are taken well diluted or on an empty stomach {16}8 {16}7 {16}6 {16}5 {16}4 {16}3 {16}2 {16}1 {16}0 {117}9.

Distribution:

Rapidly distributed to all tissues and fluids with high concentrations in the brain, liver, and kidneys {117}8 {117}7 {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {16}9 {16}8 {16}7 {16}6 {16}5 {16}4 {16}3 {16}2.

Lipid solubility is the primary factor in distribution within the body. The more lipid soluble the barbiturate, the more rapidly it penetrates all tissues of the body; phenobarbital has the lowest lipid solubility and secobarbital the highest {16}1 {16}0 {16}9 {16}8 {16}7 {16}6 {16}5 {16}4 {16}3 {16}2 {16}1 {16}0 {167}9 {167}8.

Biotransformation:

Hepatic, primarily by the hepatic microsomal enzyme system {167}7 {167}6 {167}5 {167}4 {167}3 {167}2 {167}1 {167}0 {04}9 {04}8 {04}7 {04}6 {04}5 {04}4 {04}3 {04}2 {04}1 {04}0.

About 75% of a single oral dose of mephobarbital is metabolized to phenobarbital in 24 hours {04}9 {04}8.

Metharbital is metabolized to barbital {04}7 {04}6.

Onset of action:

Oral or rectal—Varies from 20 to 60 minutes {04}5 {04}4 {04}3 {04}2.

Intramuscular—Slightly faster than for oral or rectal {04}1 {04}0 {13}9 {13}8.

Intravenous—Ranges from almost immediately for pentobarbital sodium to 5 minutes for phenobarbital sodium {13}7 {13}6 {13}5 {13}4 {13}3.

Therapeutic serum concentration

Anticonvulsant—Phenobarbital: 10 to 40 mcg per mL (43 to 172 micromoles/L) {13}2.

Note: The optimal blood phenobarbital concentration should be determined by response in seizure control and the appearance of toxic effects.
To achieve blood concentrations considered therapeutic in children, higher-per-kg dosages of phenobarbital and most other anticonvulsants generally are required {13}1 {13}0.


Time to peak effect:

Phenobarbital—Maximal CNS depression may not occur for 15 minutes or more after intravenous administration of phenobarbital sodium {113}9 {113}8 {113}7 {113}6 {113}5.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to one of the barbiturates may be sensitive to other barbiturates also.

Carcinogenicity/Tumorigenicity/Mutagenicity

For butabarbital and secobarbital—No long-term studies in animals have been done to determine the carcinogenic and mutagenic potential of butabarbital or secobarbital {113}4 {113}3 {113}2 {113}1.

For pentobarbital—Adequate studies have not been done in humans or animals to determine the carcinogenic potential of pentobarbital {113}0 {98}9 {98}8 {98}7 {98}6.

For phenobarbital—Studies in animals have shown that phenobarbital is carcinogenic in mice and rats following lifetime administration. It produced benign and malignant liver cell tumors in mice and benign liver cell tumors very late in life in rats. A study in humans did not provide sufficient evidence that phenobarbital is carcinogenic in humans. {98}5 {98}4 {98}3 {98}2 {98}1

Pregnancy/Reproduction
Fertility—
For butabarbital: No long-term studies in animals have been done to determine the effects of butabarbital on fertility {98}0.

Pregnancy—
Barbiturates readily cross the placenta following oral or parenteral administration. They are distributed throughout fetal tissues, the highest concentrations being found in the placenta, fetal liver, and brain. {118}9 {118}8 {118}7 {118}6 Following parenteral administration, fetal blood concentration approaches maternal blood concentration {118}5 {118}4 {118}3 {118}2 {118}1 {118}0 {05}9 {05}8 {05}7 {05}6 {05}5 {05}4 {05}3 {05}2.


Barbiturates have been shown to cause an increased incidence of fetal abnormalities. Risk-benefit must be carefully considered when the medication is required in life-threatening situations or in serious diseases for which other medications cannot be used or are ineffective. {05}1 {05}0 {58}9 {58}8 {58}7 {58}6 {58}5 {58}4 {58}3 {58}2 {58}1 {58}0 {117}9 {117}8 {117}7 {117}6

Third trimester: Use of barbiturates throughout the last trimester of pregnancy may cause physical dependence with resulting withdrawal symptoms in the neonate. In infants suffering from long-term exposure in utero, the acute withdrawal syndrome of seizures and hyperirritability has been reported to occur from birth to a delayed onset of up to 14 days. {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {17}9 {17}8 {17}7 {17}6 {17}5 {17}4 {17}3

Use of long-acting barbiturates, especially phenobarbital, as anticonvulsants during pregnancy is reportedly associated with a neonatal coagulation defect that may cause bleeding during the early neonatal period (usually within 24 hours of birth). This coagulation defect is characterized by decreased concentrations of vitamin K–dependent clotting factors and prolongation of the prothrombin time and/or the partial thromboplastin time. Vitamin K should be given to the mother during delivery and to the infant (intramuscularly or subcutaneously) immediately after birth. {17}2 {17}1 {17}0 {40}9 {40}8 {40}7 {40}6 {40}5

Also, one study in humans has suggested that prenatal exposure to barbiturates may be associated with an increased incidence of brain tumors {40}4 {40}3 {40}2 {40}1 {40}0 {55}9 {55}8 {55}7 {55}6 {55}5 {55}4 {55}3.

FDA Pregnancy Category D {55}2 {55}1 {55}0 {99a}9 {99a}8 {99a}7 {99a}6 {99a}5 {99a}4 {99a}3 {99a}2 {99a}1 {99a}0 {117}9 {117}8 {117}7.


Labor and delivery—

Barbiturates in hypnotic doses do not appear to inhibit uterine activity; however, full anesthetic doses of barbiturates decrease the force and frequency of uterine contractions {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8 {119}7 {119}6 {119}5 {119}4 {119}3 {119}2.

Use of barbiturates during labor may cause respiratory depression in the neonate, especially the premature neonate, because of immature hepatic function {119}1 {119}0 {17}9 {17}8 {17}7 {17}6 {17}5 {17}4 {17}3 {17}2 {17}1 {17}0 {113}9 {113}8 {113}7 {113}6 {113}5 {113}4 {113}3 {113}2 {113}1.

If barbiturates are used during labor and delivery, it is recommended that resuscitation equipment be readily available {113}0 {17}9 {17}8 {17}7 {17}6 {17}5 {17}4 {17}3 {17}2 {17}1 {17}0 {40}9 {40}8 {40}7 {40}6 {40}5.

Breast-feeding

Barbiturates are distributed into breast milk; use by nursing mothers may cause CNS depression in the infant {40}4 {40}3 {40}2 {40}1 {40}0 {55}9 {55}8 {55}7 {55}6 {55}5 {55}4 {55}3 {55}2 {55}1 {55}0.

Pediatrics

Some children may react to barbiturates with paradoxical excitement.


Geriatrics


Geriatric patients may react to usual doses of barbiturates with excitement, confusion, or mental depression {99a}9 {99a}8 {99a}7 {99a}6 {99a}5 {99a}4 {99a}3 {99a}2 {99a}1 {99a}0 {117}9 {117}8 {117}7 {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8 {119}7 {119}6 {119}5 {119}4.

The risk of barbiturate-induced hypothermia may be increased in elderly patients, especially with high doses or in acute overdose of barbiturates.

In addition, elderly patients are more likely to have age-related hepatic or renal function impairment, which may require a reduction of dosage in patients receiving a barbiturate {119}3 {119}2 {119}1 {119}0 {02}9 {02}8 {02}7.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Acetaminophen    (therapeutic effects of acetaminophen may be decreased when the medication is used concurrently in patients receiving chronic barbiturate therapy because of increased metabolism resulting from induction of hepatic microsomal enzymes; also, risk of hepatotoxicity with single toxic doses or prolonged use of high doses of acetaminophen may be increased in alcoholics or in patients regularly using hepatic enzyme inducers such as barbiturates {02}6 {02}5 {02}4 {02}3 {02}2)


Addictive medications, other, especially CNS depressants with habituating potential    (prolonged concurrent use may increase the risk of habituation; caution is recommended {02}1)


» Adrenocorticoids, glucocorticoid and mineralocorticoid{02}0{04}9{04}8{04}7{04}6{04}5{04}4{04}3{04}2{04}1{04}0{13}9{13}8{13}7{13}6{13}5{13}4{13}3{13}2{13}1{13}0{168}9{168}8{168}7{168}6{168}5{168}4{168}3 or
Chloramphenicol{168}2{168}1{168}0{01}9{01}8 or
» Corticotropin{01}7{01}6{01}5{01}4{01}3{01}2{01}1{01}0{17}9{17}8{17}7{17}6 or
Cyclosporine{17}5{17}4 or
Dacarbazine{17}3 or
Digitalis glycosides{17}2{17}1{17}0{40}9 or
Metronidazole{40}8{40}7{40}6{40}5{40}4{40}3{40}2 or
Quinidine{40}1{40}0{55}9    (effects may be decreased when these medications are used concurrently with barbiturates, especially phenobarbital, because of enhanced metabolism resulting from induction of hepatic microsomal enzymes; dosage adjustment of these medications, with the exception of digoxin, may be necessary {55}8 {55}7 {55}6 {55}5 {55}4 {55}3 {55}2 {55}1 {55}0 {99a}9 {99a}8)


» Alcohol{99a}7{99a}6{99a}5{99a}4{99a}3{99a}2{99a}1{99a}0{117}9{117}8{117}7{117}6{117}5 or
» CNS depression–producing medications, other (See Appendix II )    (concurrent use may increase the CNS depressant effects of either these medications or barbiturates; caution is recommended and dosage of one or both agents should be reduced {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8 {119}7 {119}6 {119}5 {119}4 {119}3 {119}2 {119}1 {119}0 {99}9 {99}8 {99}7 {99}6 {99}5 {99}4 {99}3 {99}2 {99}1 {99}0 {111}9 {111}8 {111}7 {111}6)


Amphetamines{111}5    (concurrent use may cause a delay in the intestinal absorption of phenobarbital {111}4 {111}3)


Anesthetics, halogenated hydrocarbon{111}2{111}1    (chronic use of barbiturates prior to enflurane, halothane, or methoxyflurane anesthesia may increase anesthetic metabolism leading to increased risk of hepatotoxicity {111}0 {111}9)

    (chronic use of barbiturates prior to methoxyflurane anesthesia may increase formation of nephrotoxic metabolites leading to increased risk of nephrotoxicity {111}8 {111}7)


» Anticoagulants, coumarin- or indandione-derivative{111}6{111}5{111}4    (effects may be decreased when these medications are used concurrently with barbiturates because of increased metabolism resulting from induction of hepatic microsomal enzymes; also, bleeding may result when the barbiturate is discontinued {111}3; periodic prothrombin-time determinations may be required to determine if dosage adjustments of anticoagulants are necessary {111}2 {111}1 {111}0 {18}9 {18}8 {18}7 {18}6 {18}5 {18}4 {18}3 {18}2 {18}1 {18}0 {40}9 {40}8 {40}7 {40}6 {40}5 {40}4 {40}3 {40}2 {40}1 {40}0 {41}9 {41}8 {41}7 {41}6 {41}5 {41}4 {41}3)


Anticonvulsants, hydantoin{41}2{41}1{41}0    (concurrent use with barbiturates appears to produce variable and unpredictable effects on the metabolism of hydantoin anticonvulsants; blood concentrations of hydantoin anticonvulsants should be closely monitored when these medications are used concurrently {55}9 {55}8 {55}7 {55}6 {55}5 {55}4 {55}3 {55}2 {55}1 {55}0 {117}9 {117}8 {117}7 {117}6 {117}5 {117}4 {117}3 {117}2)


Anticonvulsants, succinimide or{117}1{117}0
» Carbamazepine{119}9{119}8{119}7    (concurrent use with barbiturates may result in increased metabolism, leading to decreased serum concentrations and reduced elimination half-lives of carbamazepine or succinimide anticonvulsants because of induction of hepatic microsomal enzyme activity; monitoring of serum concentrations as a guide to dosage is recommended, especially when carbamazepine or a succinimide anticonvulsant is added to or withdrawn from an existing regimen {119}6 {119}5 {119}4 {119}3 {119}2 {119}1)


Antidepressants, tricyclic{119}0{18}9{18}8    (effects of tricyclic antidepressants may be decreased when these medications are used concurrently with barbiturates, especially phenobarbital, because of increased metabolism resulting from induction of hepatic microsomal enzymes {18}7 {18}6)


Calcium channel blocking agents{18}5{18}4{18}3    (caution is advised during titration of calcium channel blocker dosage for those patients taking medication known to promote hypotension, such as barbiturate preanesthetics, since the combination may result in excessive hypotension {18}2 {18}1)


Carbonic anhydrase inhibitors{18}0    (osteopenia induced by barbiturates, especially phenobarbital, may be enhanced when carbonic anhydrase inhibitors are used concurrently; it is recommended that patients receiving concurrent therapy be monitored for early signs of osteopenia and that the carbonic anhydrase inhibitor be discontinued and appropriate treatment initiated if necessary {40}9 {40}8)


» Contraceptives, estrogen-containing, oral{40}7{40}6    (concurrent use with barbiturates, especially phenobarbital, may result in reduced contraceptive reliability because of accelerated estrogen metabolism caused by induction of hepatic microsomal enzymes; use of a nonhormonal method of birth control or a progestin-only oral contraceptive may be necessary {40}5 {40}4 {40}3 {40}2 {40}1 {40}0 {41}9 {41}8 {41}7 {41}6 {41}5 {41}4 {41}3 {41}2 {41}1 {41}0 {55}9 {55}8 {55}7 {55}6)


Cyclophosphamide{55}5{55}4    (concurrent use with barbiturates, especially phenobarbital, may induce microsomal metabolism to increase formation of alkylating metabolites of cyclophosphamide, thereby reducing the half-life and increasing the leukopenic activity of cyclophosphamide {55}3)


Disopyramide{55}2    (concurrent use with barbiturates, especially phenobarbital, may reduce serum disopyramide to ineffective concentrations; therefore, monitoring of its serum concentrations is necessary during concurrent therapy {55}1)


» Divalproex sodium{55}0 or
» Valproic acid{117}9{117}8{117}7    (concurrent use may decrease the metabolism of barbiturates, resulting in increased serum {117}6 concentrations, which may lead to increased CNS depression and neurological toxicity; barbiturate serum {117}5 concentrations should be monitored to determine if dosage adjustment is necessary when these medications are used concurrently; also, the half-life of valproic acid may be decreased and dosage adjustment may be necessary {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8 {119}7 {119}6 {119}5 {119}4 {119}3 {119}2 {119}1)

    (in addition, phenobarbital may enhance valproic acid hepatotoxicity, presumably through the formation of hepatotoxic valproate metabolites {119}0 {18}9)


Doxycycline{18}8{18}7{18}6    (half-life of doxycycline may be shortened when this medication is used concurrently with barbiturates, especially phenobarbital, probably because of increased metabolism resulting from induction of hepatic microsomal enzymes; this effect may continue for up to 2 weeks after barbiturate therapy is discontinued; adjustment of doxycycline dosage during and after therapy or substitution of another tetracycline may be necessary {18}5 {18}4 {18}3 {18}2 {18}1 {18}0 {40}9 {40}8 {40}7 {40}6 {40}5 {40}4 {40}3 {40}2 {40}1 {40}0 {55}9)


Fenoprofen{55}8{55}7    (concurrent use with phenobarbital may decrease the elimination half-life of fenoprofen, possibly because of increased metabolism resulting from induction of hepatic microsomal enzyme activity; fenoprofen dosage adjustment may be required {55}6)


Griseofulvin{55}5{55}4{55}3    (absorption may be decreased when this medication is used concurrently with barbiturates, especially phenobarbital, resulting in decreased serum concentrations; although the effect of decreased serum {55}2 concentrations on therapeutic response has not been established, concurrent use preferably should be avoided {55}1 {55}0 {117}9 {117}8 {117}7 {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8 {119}7 {119}6)


Guanadrel{119}5 or
Guanethidine{119}4    (concurrent use with barbiturates may aggravate orthostatic hypotension {119}3 {119}2)


Haloperidol{119}1{119}0    (concurrent use with barbiturate anticonvulsants may cause a change in the pattern and/or frequency of epileptiform seizures; dosage adjustments of anticonvulsants may be necessary; serum concentrations of haloperidol may be significantly reduced {18}9)


Hypothermia-producing medications, other (See Appendix II )    (concurrent use with barbiturates in high doses or acute overdose may increase the risk of hypothermia)


Ketamine{18}8    (concurrent use of ketamine, especially in high doses or when rapidly administered, with barbiturate preanesthetics may increase the risk of hypotension and/or respiratory depression {18}7)


Leucovorin{18}6    (large doses may counteract the anticonvulsant effects of barbiturate anticonvulsants {18}5)


Levothyroxine{18}4    (concurrent use of barbiturates may increase hepatic degradation of levothyroxine, which may result in increased requirements; dosage adjustment may be necessary {18}3 {18}2)


Loxapine{18}1 or
Phenothiazines{18}0{40}9{40}8 or
Thioxanthenes{40}7    (may lower the seizure threshold; dosage adjustment of barbiturate anticonvulsants may be necessary {40}6 {40}5 {40}4)

    (concurrent use of chlorpromazine with phenobarbital has been shown to increase the metabolism {40}3 of chlorpromazine; therefore, phenobarbital may decrease serum concentrations of phenothiazines when used concurrently {40}2 {40}1 {40}0)


Maprotiline{41}9    (in addition to possibly enhancing CNS depressant effects, concurrent use of maprotiline may lower the convulsive threshold, at high doses, and decrease the effects of barbiturate anticonvulsants {41}8)


Methylphenidate{41}7    (concurrent use may increase serum concentrations of barbiturate anticonvulsants, especially phenobarbital, because of metabolism inhibition, possibly resulting in toxicity; dosage adjustment of the barbiturate anticonvulsant may be necessary {41}6)


Mexiletine{41}5    (concurrent use with barbiturates may accelerate metabolism and result in decreased plasma concentrations of mexiletine; plasma concentrations of mexiletine should be monitored during concurrent use to ensure efficacy is maintained {41}4 {41}3)


Monoamine oxidase (MAO) inhibitors, including furazolidone, pargyline, and procarbazine{41}2{41}1{41}0    (concurrent use may prolong the CNS depressant effects of barbiturates, probably because metabolism of the barbiturate is inhibited {55}9 {55}8 {55}7 {55}6 {55}5 {55}4 {55}3 {55}2 {55}1 {55}0 {58}9 {58}8 {58}7 {58}6)

    (concurrent use with barbiturate anticonvulsants may cause a change in the pattern of epileptiform seizures; dosage adjustment of the barbiturate anticonvulsant may be necessary {58}5 {58}4)


Phenylbutazone{58}3{58}2{58}1    (concurrent use may decrease the efficacy of barbiturates by inducing hepatic microsomal enzymes and increasing their metabolism; also, hepatic enzyme inducers such as barbiturates may increase phenylbutazone metabolism and decrease its half-life {58}0 {117}9)


Posterior pituitary{117}8    (concurrent use with barbiturates may increase the risk of cardiac arrhythmias and coronary insufficiency {117}7)


Primidone{117}6{117}5    (although concurrent use with barbiturate anticonvulsants is rarely indicated, since primidone is metabolized to phenobarbital {117}4, it may cause a change in the pattern of epileptiform seizures because of altered medication metabolism and also increase the sedative effect of either primidone or the barbiturate anticonvulsant {117}3; decreases in primidone dosage may be necessary {117}2)


Rifampin{117}1{117}0{119}9    (concurrent use with rifampin may enhance the metabolism of hexobarbital by induction of hepatic microsomal enzymes, resulting in lower serum concentrations; there are conflicting data on rifampin's effect on phenobarbital; dosage adjustment may be required)


Vitamin D{119}8    (effects may be reduced by barbiturates, especially phenobarbital, because of accelerated metabolism by hepatic microsomal enzyme induction; vitamin D supplementation may be required in patients on long-term barbiturate anticonvulsant therapy to prevent osteomalacia, although rickets is rare {119}7 {119}6 {119}5)


Xanthines, such as{119}4{119}3{119}2 :
Aminophylline
Caffeine
Oxtriphylline
Theophylline    (concurrent use with barbiturates, especially phenobarbital, may increase metabolism of the xanthines [except dyphylline] by induction of hepatic microsomal enzymes, resulting in increased theophylline clearance; also, concurrent use may antagonize hypnotic effects of barbiturates {119}1 {119}0)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Cyanocobalamin Co 57    (absorption of radioactive cyanocobalamin may be impaired by concurrent use of barbiturate anticonvulsants, especially phenobarbital)


Metyrapone test    (increased metabolism of metyrapone by an hepatic enzyme inducer such as a barbiturate may decrease the response to metyrapone {01}9)


Phentolamine test    (barbiturates may cause a false-positive phentolamine test; it is recommended that all medications be withdrawn at least 24 hours, preferably 48 to 72 hours, prior to a phentolamine test)

With physiology/laboratory test values
Bilirubin, serum    (concentrations may be decreased in neonates, in patients with congenital nonhemolytic unconjugated hyperbilirubinemia, and in epileptics; this effect is presumably due to induction of glucuronyl transferase, the enzyme responsible for the conjugation of bilirubin)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Porphyria, acute intermittent or variegata, or history of    (barbiturates may aggravate symptoms by inducing enzymes responsible for porphyrin synthesis {01}8 {01}7 {01}6 {01}5 {01}4 {01}3 {01}2 {01}1 {01}0 {40}9 {40}8 {40}7 {40}6 {40}5 {40}4 {40}3 {40}2 {40}1 {40}0 {55}9 {55}8 {55}7 {55}6 {55}5 {55}4 {55}3 {55}2 {55}1 {55}0 {58}9 {58}8 {58}7 {58}6)


Risk-benefit should be considered when the following medical problems exist
Anemia, severe    (may be complicated by barbiturate-induced respiratory depression, especially with phenobarbital)


Asthma, history of    (hypersensitivity reactions such as bronchospasm more likely to occur in these patients {58}5 {58}4 {58}3 {58}2)


Diabetes mellitus, especially with phenobarbital
» Drug abuse or dependence, history of    (predisposition of patient to habituation and dependence {58}1 {58}0 {117}9 {117}8 {117}7 {117}6 {117}5 {117}4 {117}3 {117}2 {117}1 {117}0 {119}9 {119}8 {119}7 {119}6 {119}5 {119}4 {119}3)


» Hepatic coma, premonitory signs of, or
Hepatic function impairment    (barbiturates metabolized in liver; medication should be administered with caution and, initially, in reduced dosage {119}2 {119}1 {119}0 {04}9 {04}8 {04}7 {04}6 {04}5 {04}4 {04}3 {04}2 {04}1 {04}0 {19}9 {19}8 {19}7 {19}6 {19}5 {19}4 {19}3 {19}2 {19}1 {19}0 {113}9 {113}8 {113}7 {113}6 {113}5 {113}4 {113}3 {113}2)


Hyperkinesis    (condition may be exacerbated)


Hyperthyroidism    (symptoms may be exacerbated because barbiturates displace thyroxine from plasma proteins)


Hypoadrenalism, borderline    (systemic effects of exogenous hydrocortisone and endogenous cortisol may be diminished by barbiturates {113}1 {113}0 {168}9 {168}8 {168}7 {168}6 {168}5 {168}4 {168}3 {168}2 {168}1 {168}0)


Mental depression and/or
Suicidal tendencies    (condition may be exacerbated, especially in elderly patients {04}9 {04}8 {04}7 {04}6 {04}5 {04}4 {04}3 {04}2 {04}1 {04}0 {40}9 {40}8 {40}7 {40}6)


» Pain, acute or chronic    (paradoxical excitement may be induced or important symptoms may be masked {40}5 {40}4 {40}3 {40}2 {40}1 {40}0 {58}9 {58}8 {58}7 {58}6 {58}5 {58}4 {58}3 {58}2 {58}1 {58}0 {113}9 {113}8 {113}7 {113}6 {113}5 {113}4 {113}3 {113}2 {113}1 {113}0 {04}9 {04}8 {04}7)


Renal function impairment, especially with intermediate- and long-acting barbiturates    (barbiturates excreted primarily by kidneys; dosage reduction may be necessary {04}6 {04}5 {04}4)


» Respiratory disease involving dyspnea or obstruction, particularly status asthmaticus    (serious ventilatory depression may occur {04}3 {04}2 {04}1 {04}0 {40}9 {40}8 {40}7 {40}6 {40}5 {40}4 {40}3 {40}2 {40}1 {40}0 {58}9 {58}8 {58}7 {58}6)


» Sensitivity to barbiturate prescribed    (in patients sensitive to barbiturates, severe hepatic damage can occur from ordinary doses and is usually associated with dermatitis and involvement of parenchymatous organs {58}5 {58}4 {58}3 {58}2 {58}1 {58}0 {113}9 {113}8 {113}7 {113}6 {113}5 {113}4 {113}3 {113}2)


Caution should be used also in debilitated patients because they may react to usual doses with marked excitement, mental depression, and confusion{113}1{113}0{18}9{18}8{18}7{18}6{18}5{18}4{18}3{18}2{18}1{18}0{41}9{41}8
For parenteral dosage forms only:
Cardiac disease    (adverse circulatory reactions may occur with intravenous administration, especially with too-rapid administration)


Hypertension    (hypotension may occur with intravenous administration, especially in these patients; slow administration usually prevents this occurrence)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Folate concentrations, serum    (determinations recommended periodically because of increased folate requirements of patients on long-term anticonvulsant therapy with phenobarbital and possibly mephobarbital {41}7)


Hematopoietic function and
Hepatic function and
Renal function    (determinations recommended at periodic intervals during prolonged barbiturate therapy {41}6 {41}5 {41}4 {41}3 {41}2 {41}1 {41}0 {55}9 {55}8 {55}7 {55}6 {55}5 {55}4 {55}3 {55}2 {55}1 {55}0 {117}9)


Barbital concentrations, serum    (determinations recommended when clinically indicated during metharbital therapy)


Phenobarbital concentrations, serum    (determinations recommended as clinically indicated when phenobarbital or mephobarbital is used as an anticonvulsant)




Side/Adverse Effects

Note: Exfoliative dermatitis and Stevens-Johnson syndrome, possibly fatal, may occur rarely as hypersensitivity reactions to barbiturates. If dermatologic reactions occur, the barbiturate should be discontinued.
Severe respiratory depression, apnea, laryngospasm, bronchospasm, or hypertension may occur with intravenous administration of barbiturates, especially if administered too rapidly {117}8 {117}7 {117}6 {117}5 {117}4 {117}3 {117}2.
Prolonged barbiturate therapy may result in osteopenia or rickets {117}1.
Barbiturate dependence may occur, especially following prolonged use of high doses. The characteristics of dependence include: a strong desire or need to continue taking the barbiturate; a tendency to increase the dose; a psychological dependence on the effects of the medication; and a physical dependence on the effects of the medication requiring its presence for maintenance of homeostasis and resulting in an abstinence syndrome when the barbiturate is discontinued. Symptoms of withdrawal are related to the pharmacokinetics of the specific barbiturate and can be severe and may even cause death. {117}0 {19}9 {19}8 {19}7 {19}6 {19}5 {19}4 {19}3 {19}2 {19}1

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Sensitivity to barbiturates (confusion)—especially in geriatric or debilitated patients{19}0{99}9{99}8{99}7{99}6
    
mental depression —especially in geriatric or debilitated patients
    
paradoxical reaction (unusual excitement)—especially in children or geriatric or debilitated patients{99}5{99}4{99}3{99}2{99}1{99}0{99a}9{99a}8{99a}7{99a}6

Incidence rare
    
Agranulocytosis (sore throat and/or fever)
    
allergic reaction (skin rash or hives; swelling of eyelids, face, or lips; wheezing or tightness in chest)—especially in patients who have asthma, urticaria, angioedema, and similar conditions
    
exfoliative dermatitis (fever; red, thickened, or scaly skin)
    
hallucinations
    
hypotension or megaloblastic anemia (unusual tiredness or weakness)—with chronic barbiturate use
    
Stevens-Johnson syndrome (bleeding sores on lips; chest pain; muscle or joint pain; painful sores, ulcers, or white spots in mouth; skin rash or hives; sore throat or fever){99a}5
    
thrombocytopenia (unusual bleeding or bruising)
    
thrombophlebitis (soreness, redness, swelling, or pain at injection site)—for parenteral dosage forms only

With prolonged or chronic use
    
Hepatic damage (yellow eyes or skin)
    
osteopenia or rickets (bone pain, tenderness, or aching; loss of appetite; muscle weakness; unusual weight loss)

{99a}4{99a}3{99a}2{99a}1{99a}0{51}9{51}8{51}7{51}6{51}5{51}4{51}3{51}2{51}1{51}0

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Clumsiness or unsteadiness
    
dizziness or lightheadedness
    
drowsiness
    
``hangover'' effect

Incidence less frequent
    
Anxiety or nervousness
    
constipation
    
feeling faint
    
headache
    
irritability
    
nausea or vomiting
    
nightmares or trouble in sleeping

{20}9{20}8{20}7{20}6{20}5{20}4{20}3{20}2{20}1{20}0{42}9{42}8{42}7{42}6{42}5{42}4{42}3{42}2{42}1{42}0{59}9{59}8{59}7{59}6

Those indicating possible barbiturate withdrawal and need for medical attention if they occur after medication is discontinued
Minor symptoms
—may occur within 8 to 12 hours and usually occur in the following sequence:    
Anxiety or restlessness
    
muscle twitching
    
trembling of hands
    
weakness
    
dizziness
    
vision problems
    
nausea
    
vomiting
    
trouble in sleeping, increased dreaming, or nightmares
    
orthostatic hypotension (feeling faint; lightheadedness)

Major symptoms
—may occur within 16 hours and last up to 5 days    
Convulsions
    
hallucinations
{59}5{59}4{59}3{59}2{59}1{59}0{101}9{101}8

Note: Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days {101}7 {101}6 {101}5.

{101}4{101}3{101}2{101}1{101}0{112}9{112}8{112}7{112}6{112}5{112}4{112}3{112}2{112}1{112}0{121}9{121}8{121}7{121}6{121}5{121}4{121}3
{121}2{121}1{121}0{121}9{121}8{121}7{121}6{121}5{121}4{121}3{121}2{121}1{121}0{121}9{121}8


Overdose
For specific information on the agents used in the management of barbiturate overdose, see:
   • Charcoal, Activated (Oral-Local) monograph; and/or
   • Ipecac (Oral-Local) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
    
Confusion, severe
    
decrease in or loss of reflexes {121}7
    
drowsiness, severe
    
fever {121}6
    
hypothermia ( low body temperature){121}5
    
shortness of breath or slow or troubled breathing
    
slow heartbeat
    
slurred speech
    
staggering
    
unusual movements of the eyes
    
weakness, severe
{121}4{121}3{121}2{121}1{121}0{101}9{101}8{101}7{101}6{101}5{101}4{101}3{101}2{101}1{101}0{102}9{102}8{102}7{102}6{102}5{102}4{102}3{102}2{102}1{102}0{112}9{112}8

Note: In acute barbiturate overdosage, CNS and respiratory depression may progress to Cheyne-Stokes respiration, areflexia, slight constriction of the pupils (in severe toxicity, pupils may be dilated), oliguria, tachycardia, lowered body temperature, and coma. Typical shock syndrome (apnea, circulatory collapse, respiratory arrest, and death) may occur. {112}7 {112}6 {112}5 {112}4 {112}3 {112}2
In extreme barbiturate overdosage, all electrical activity in the brain may cease. In this case an electroencephalogram (EEG) may be ``flat,"" but this does not necessarily indicate clinical death since, unless hypoxic damage occurs, this effect is fully reversible. {112}1 {112}0 {112}9 {112}8 {112}7 {112}6 {112}5 {112}4 {112}3 {112}2 {112}1
Complications in barbiturate overdosage such as pneumonia, pulmonary edema, cardiac arrhythmias, congestive heart failure, and renal failure may occur {112}0 {57} {84} {90} {92} {95} {115} {117} {119}.
In acute overdosage, the blood barbiturate concentration for some of the barbiturates relative to the degree of CNS depression in nontolerant persons is as follows:

Table 2. General Dosing Information



Drug
Onset/Duration
of Action
Barbiturate Blood Concentrations (mcg/mL)
Categories of Degree of CNS Depression *

(1)
(2)
(3)
(4)
(5)
Pentobarbital
Fast/short
£2
0.5–3
10–15
12–25
15–40
Secobarbital
Fast/short
£2
0.5–5
10–15
15–25
15–40
Amobarbital
Intermediate/
£3
2–10
30–40
30–60
40–80
  intermediate
         
Butabarbital
Intermediate/
£5
3–25
40–60
50–80
60–100
  intermediate
         
Phenobarbital
Slow/long
£10
5–40
50–80
70–120
100–200
* Categories of degree of CNS depression in nontolerant persons:

• (1) Under the influence and appreciably impaired for purposes of driving a motor vehicle or performing tasks requiring alertness and unimpaired judgment and reaction time.


• (2) Sedated, therapeutic range, calm, relaxed, and easily aroused.


• (3) Comatose, difficult to arouse, and significant respiratory depression.


• (4) Comparable with death in aged or ill persons or in presence of obstructed airway, other toxic agents, or exposure to cold.


• (5) Usual lethal concentration, the upper end of the range includes those who received some supportive treatment



Chronic
    
Confusion, severe
    
irritability, continuing
    
poor judgment
    
trouble in sleeping
{84}{90}{92}{99a}{115}{116}{117}

Treatment of overdose
Treatment of barbiturate overdose is primarily supportive and consists of the following {46} {48} {51} {52} {53} {54} {55} {56} {57} {58} {59} {60} {69} {70} {84} {90} {92} {95} {99a} {114} {115} {116} {117} {118} {119} {120} {121}


To decrease absorption:
If the patient is conscious and has not lost the gag reflex, emesis may be induced with ipecac syrup; care should be taken to prevent pulmonary aspiration of vomitus. After vomiting is completed, 30 {90} {92} to 60 grams of activated charcoal in a glass of water or sorbitol may be administered to prevent absorption and increase excretion of the barbiturate. {84} {90} {92} {95} {115} {116}

If emesis is contraindicated, gastric lavage may be performed with a cuffed endotracheal tube in place with the patient face down {69} {70} {84} {90} {92} {95} {114} {115}. Activated charcoal should be left in the stomach and a saline cathartic may be administered {84} {115} {116}.



To enhance elimination:
If renal function is normal, forced diuresis may help to eliminate the barbiturate {84} {90} {92} {115} {116}.

Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital, also aprobarbital, and mephobarbital (which is metabolized to phenobarbital) {84} {90} {92} {95}.

Although hemodialysis {90} {92} or hemoperfusion is not recommended as a routine procedure, it may be used in severe barbiturate poisoning or if the patient is anuric or in shock {69} {70} {84} {90} {92} {95} {114} {116}.



Monitoring:
Vital signs and fluid balance should be monitored {84} {90} {92} {115} {116}.



Supportive care:
An adequate airway should be maintained, with assisted respiration and administration of oxygen as needed {69} {70} {84} {90} {92} {95} {115} {116}.

Blood pressure and body temperature should be maintained {40} {69} {70} {95} {114}.

Fluid therapy and other standard treatment for shock should be administered, if necessary {69} {70} {84} {90} {92} {95} {114} {115} {116}.

A vasopressor may be required if hypotension occurs {95}.

Fluid or sodium overload should be avoided, especially if cardiovascular status is decreased.

Chest physiotherapy should be administered.

If pneumonia is suspected, appropriate cultures should be taken and antibiotics should be administered {69} {70} {84} {90} {92} {114} {115} {116}.

Also, appropriate care should be taken to prevent hypostatic pneumonia, decubiti, aspiration, and other complications that may occur with altered states of consciousness {84} {90} {92} {115} {116}.

Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Barbiturates (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to barbiturates

Pregnancy—Barbiturates readily cross placenta; increase in incidence of fetal abnormalities (FDA Pregnancy Category D); use during third trimester of pregnancy may cause physical dependence with resulting withdrawal symptoms in neonate; long-acting barbiturates associated with neonatal coagulation defect that may cause bleeding during early neonatal period; use during labor may cause respiratory depression in neonate





Breast-feeding—Barbiturates distributed into breast milk; use by nursing mothers may cause CNS depression in infant





Use in children—Children may react to barbiturates with paradoxical excitement






Use in the elderly—Elderly patients may react to usual doses of barbiturates with excitement, confusion, or mental depression; risk of barbiturate-induced hypothermia may be increased in elderly patients; elderly patients more likely to have age-related hepatic or renal function impairment, which may require a dosage reduction of barbiturates
Other medications, especially alcohol, adrenocorticoids, corticotropin, other CNS depression–producing medications, coumarin- or indandione-derivative anticoagulants, carbamazepine, divalproex sodium, estrogen-containing contraceptives, or valproic acid
Other medical problems, especially history of drug abuse or dependence, premonitory signs of hepatic coma, acute or chronic pain, or respiratory disease involving dyspnea or obstruction (particularly status asthmaticus)

Caution if any laboratory tests required; possible interference with results of metyrapone test.

Proper use of this medication
» Importance of not using more medication than the amount prescribed because of habit-forming potential

» Not increasing dose if medication appears less effective after a few weeks; checking with physician {46} {47} {48}

» For anticonvulsant use: Compliance with therapy; not missing any doses

» Proper dosing
Missed dose: If on scheduled dosing regimen—Taking as soon as possible; not taking if almost time for next dose; not doubling doses

Proper administration

For extended-release dosage form
Swallowing capsule or tablet whole

Not breaking, crushing, or chewing

For suppository dosage form
Proper administration technique

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress during prolonged therapy

Checking with physician before discontinuing medication after prolonged use; gradual dosage reduction may be necessary to avoid the possibility of withdrawal symptoms

» Avoiding use of alcohol or other CNS depressants

» Suspected psychological or physical dependence: Checking with physician

» Suspected overdose: Getting emergency help at once

» Caution if dizziness, lightheadedness, or drowsiness occurs

» Use of another or additional method of contraception if taking estrogen-containing oral contraceptives concurrently


Side/adverse effects
Signs of potential side effects, especially allergic reaction or intolerance to barbiturate, blood dyscrasias, exfoliative dermatitis, hallucinations, hepatic damage (with prolonged or chronic use), mental depression, paradoxical reaction, osteopenia or rickets (with prolonged or chronic use), or Stevens-Johnson syndrome

Unusual excitement may be more likely to occur in children and in elderly or very ill patients

Confusion and mental depression may be more likely to occur in elderly or very ill patients


General Dosing Information
Dosage of the barbiturates must be individualized, based on the patient's age, weight, and condition {48} {49} {50} {51} {52} {53} {90} {92}.

In patients with impaired hepatic function, lower doses should be used initially. Lower doses may be required also in patients with impaired renal function. {31} {49} {51} {52} {53} {55} {90} {92} {99a}

Patients on dialysis may require an increase in dosage.

Tolerance may occur with repeated administration of the barbiturates, especially of the long-acting ones and with large doses of the shorter-acting ones {51} {55} {56} {57} {60} {84} {90} {92} {115} {116} {117} {119} {120} {121}.

Prolonged administration of barbiturates as hypnotics generally is not recommended because they have not been shown to be effective for a period of more than 2 weeks {46} {47} {51} {52} {53} {69} {70} {84} {115} {116}.

Prolonged uninterrupted use of barbiturates, particularly the short-acting ones, may result in psychic or physical dependence {46} {47} {48} {49} {51} {52} {53} {54} {55} {56} {57} {58} {59} {60} {69} {70} {84} {90} {92} {95} {99a} {114} {115} {116} {117} {118} {119} {120} {121}.

Chronic use of barbiturates at doses 3 to 4 times the therapeutic concentration will usually produce physical dependence in about 75% of patients.

Daily administration in excess of 400 mg of pentobarbital or secobarbital for approximately 90 days is likely to produce some degree of physical dependence; a dosage of 600 to 800 mg taken for at least 35 days is sufficient to produce withdrawal seizures. The average daily dose for the barbiturate addict generally is about 1.5 grams. {51} {52} {53} {55} {57} {84} {90} {92} {115}

Barbiturates should be withdrawn gradually in order to avoid the possibility of precipitating withdrawal symptoms {46} {47} {48} {49} {50} {51} {52} {53} {54} {55} {56} {84} {90} {92} {99a} {115} {116} {117} {118} {119}.

To minimize the possibility of acute or chronic overdosage, the least possible quantity of a barbiturate should be prescribed and dispensed at any one time {84}.

The toxic dose of barbiturates varies but generally an oral dose of 1 gram of most barbiturates produces serious poisoning in an adult. Death commonly occurs after 2 to 10 grams of ingested barbiturate. {48} {84} {90} {92}

Diet/Nutrition
Patients on long-term anticonvulsant therapy with phenobarbital and possibly mephobarbital may have increased folic acid requirements {171}. In addition, patients on long-term therapy may require supplements of vitamin D to prevent osteomalacia {172}.

For parenteral dosage forms only
Prior to administration, parenteral solutions should be inspected visually for particulate matter and discoloration, if possible {52} {55}.

For intravenous injections, it is preferable to use the larger veins to minimize the risk of irritation and the possibility of resulting thrombosis. Administration into varicose veins is not recommended because of poor circulation in these veins. {30} {52}

Intravenous injections should be administered slowly and patients should be carefully monitored during administration. This requires maintenance of blood pressure, respiration, and cardiac function and recording of vital signs. Equipment for resuscitation and artificial ventilation should be readily available. {52} {55}

Intramuscular injections should be administered deeply into large muscles, such as the gluteus maximus or vastus lateralis because superficial intramuscular injection may be painful and may produce sterile abscesses or sloughs. {47} {51} {55} {58} {92} {117} {119}

No more than 5 mL, regardless of drug concentration, should be injected intramuscularly at any one site because of possible tissue irritation {30} {47} {55} {114}.

Parenteral solutions of barbiturate salts are highly alkaline; therefore, caution should be used to avoid perivascular extravasation or intra-arterial injection, since extravasation may cause local tissue damage with subsequent necrosis and intra-arterial injection may cause spasm, severe pain, and possibly gangrene {55} {56} {114} {117} {119}.

For rectal dosage forms only
Barbiturates may be administered rectally when oral or parenteral administration may be undesirable. If the rectal dosage form is not available, the soluble sodium salt of the barbiturate may be incorporated in a retention enema. {117} {119}

To assure accuracy in dosage, suppositories should not be divided {53}.

Rectal administration of barbiturates is not recommended for status epilepticus; intravenous injection is the preferred route of administration for this condition.

For treatment of dependence
Treatment of dependence consists of the following {84} {90} {92} {99a} {115} {116} {117} {118} {119} {120}

   • Gradual withdrawal of the barbiturate {90} {115} {116}.
   • An example of the different withdrawal regimens used (all of which require an extended period of time) involves substituting a 30-mg dose of phenobarbital for each 100- to 200-mg dose of the barbiturate that the patient has been taking. The total daily amount of phenobarbital then is administered as a single dose or in 3 or 4 divided doses, not to exceed 600 mg per day. If signs of withdrawal occur on the first day of treatment, a loading dose of 100 to 200 mg of phenobarbital may be administered intramuscularly 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. This regimen may be modified by initiating treatment at the patient's regular dosage level and decreasing the daily dosage by 10% if tolerated by the patient. {48} {49} {51} {52} {53} {54} {55} {56} {57} {60} {84} {115} {116}
   • For infants physically dependent on barbiturates, initially a dose of 3 to 10 mg of phenobarbital per kg of body weight per day may be given. 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. {48} {49} {51} {52} {53} {54} {55} {56} {57} {58} {59} {60} {84} {90} {92} {99a} {115} {116}
   • Also, barbiturate withdrawal may be accomplished with benzodiazepines, such as diazepam {16}.

For treatment of adverse effects
For extravasation into subcutaneous tissues—Recommended treatment includes

   • Application of moist heat to affected area.
   • Injection of a 0.5% procaine solution into the affected area.
For accidental intra-arterial injection—Recommended treatment includes

   • Release of tourniquet or restrictive garments to permit dilution of injected medication.
   • Injection of 10 mL of a 1% procaine solution into the artery and, if necessary, brachial plexus block to relieve spasm.
   • Anticoagulant therapy may prevent thrombosis.
   • Supportive treatment.

AMOBARBITAL

Summary of Differences


Category:
Parenteral amobarbital also may be indicated as an anticonvulsant.



Indications:
Parenteral amobarbital also may be indicated in narcoanalysis; and has been used in diagnosis of schizophrenia and for catatonic, negativistic, and manic reactions, but generally has been replaced by other agents.



Pharmacology/pharmacokinetics:


Long-acting barbiturate—
Onset of action: 60 minutes or longer.

Duration of action: 10 to 12 hours.



Protein binding—
Moderate.




Additional Dosing Information
See also General Dosing Information.

For parenteral dosage forms only
The rate of intravenous injection should not exceed 100 mg per minute for adults or 60 mg per square meter of body surface per minute for children. Faster rates of administration may cause serious respiratory depression. {47} {114}

Superficial intramuscular or subcutaneous injections may be painful and may produce sterile abscesses or sloughs.


Oral Dosage Forms

AMOBARBITAL TABLETS USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Oral, 65 to 200 mg at bedtime {01} {02} {69} {70} {117} {119} {164}.



Sedative:
Daytime—Oral, 50 to 300 mg a day in divided doses {01} {02} {69} {70} {164}.



Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Sedative-hypnotic


Hypnotic:
Dosage has not been established {02}.



Sedative:
Daytime—Oral, 2 mg per kg of body weight or 60 mg per square meter of body surface three times a day {02} {167}.

Preoperative—Oral, 2 to 6 mg per kg of body weight, up to a maximum of 100 mg per dose {01} {55} {117} {119} {164}.



Strength(s) usually available
U.S.—
Not commercially available {69} {71}.

Canada—


30 mg (Rx) [Amytal]{104a}


100 mg (Rx) [Amytal]{104a}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.



AMOBARBITAL SODIUM CAPSULES USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Oral, 65 to 200 mg at bedtime {01} {02} {29} {55} {70} {117} {119} {164}.



Sedative:
Daytime—Oral, 50 to 300 mg a day in divided doses {01} {02} {55} {117} {119} {164}.

During labor—Oral, 200 to 400 mg, repeated every one to three hours, if necessary, up to a total dose of 1 gram {03} {29} {70}.

Preoperative—Oral, 200 mg one to two hours before surgery {03} {29} {70} {164}.



Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Sedative-hypnotic


Hypnotic:
Dosage has not been established {02}.



Sedative:
Daytime—Oral, 2 mg per kg of body weight or 60 mg per square meter of body surface three times a day {02} {167}.

Preoperative—Oral, 2 to 6 mg per kg of body weight, up to a maximum of 100 mg per dose {01}.



Strength(s) usually available
U.S.—


200 mg (Rx) [Amytal][Generic]{70}{71}{72}

Canada—


200 mg (Rx) [Amytal]{104a}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.




Parenteral Dosage Forms

AMOBARBITAL SODIUM STERILE USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Intramuscular or intravenous, 65 to 200 mg {01} {47} {114} {117} {119} .



Sedative:
Intramuscular or intravenous, 30 to 50 mg two or three times a day {55} {117} {119}.


Anticonvulsant
Intravenous, 65 to 500 mg {04} {55}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual adult prescribing limits
Intramuscular, up to 500 mg per dose {05} {47} {114}.

Intravenous, up to 1 gram per dose {05} {47} {114}.

Usual pediatric dose
Sedative-hypnotic


Hypnotic:


Children up to 6 years of age—
Intramuscular, 2 to 3 mg per kg of body weight per dose {04} {113}.



Children 6 years of age and over—
Intramuscular, 2 to 3 mg per kg of body weight per dose {04} {113}.

Intravenous, 65 to 500 mg per dose {02} {04} {114}.




Sedative:


Preoperative—
Intravenous, 65 to 500 mg or 3 to 5 mg per kg of body weight per dose {01} {55} {117} {119}.



Anticonvulsant


Children up to 6 years of age:
Intramuscular or intravenous, 3 to 5 mg per kg of body weight or 125 mg per square meter of body surface per dose {04} {167}.



Children 6 years of age and over:
Intravenous, 65 to 500 mg per dose {05} {47} {113} {114} {167}.



Size(s) usually available:
U.S.—


500 mg (Rx) [Amytal]{71}{114}

Canada—


500 mg (Rx) [Amytal]{104a}

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
Solutions of amobarbital sodium should be prepared aseptically with sterile water for injection {114}. For preparation of various concentrations of solutions for injection, see the manufacturer's package insert {114}.

Stability:
After reconstitution, solution should be used within 30 minutes since amobarbital sodium hydrolyzes in solution or upon exposure to air. Solution should not be used if it does not become absolutely clear within 5 minutes after reconstitution or if a precipitate forms after the solution clears. {47} {114}

Note: Controlled substance in the U.S. and Canada.



APROBARBITAL

Summary of Differences


Pharmacology/pharmacokinetics:


Intermediate-acting barbiturate—
Onset of action: 45 to 60 minutes.

Duration of action: 6 to 8 hours.



Protein binding—
Low.




Oral Dosage Forms

APROBARBITAL ELIXIR

Usual adult dose
Sedative-hypnotic
Hypnotic: Oral, 40 to 160 mg at bedtime {06} {31} {55} {117} {119}.

Sedative: Daytime—Oral, 40 mg three times a day {06} {55} {117} {119}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Dosage has not been established {06}.

Strength(s) usually available
U.S.—


40 mg per 5 mL (Rx) [Alurate (alcohol 20%) (dextrose) (saccharin) (sorbitol) (sucrose) (FD&C Yellow No. 6) (FD&C Red No. 40)]{73}{73a}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight, light-resistant container, unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.
   • Keep container tightly closed.

Note: Controlled substance in the U.S.



BUTABARBITAL

Summary of Differences


Pharmacology/pharmacokinetics:


Intermediate-acting barbiturate—
Onset of action: 45 to 60 minutes.

Duration of action: 6 to 8 hours.



Protein binding—
Low.




Oral Dosage Forms

BUTABARBITAL SODIUM ELIXIR USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Oral, 50 to 100 mg at bedtime {07} {32} {48} {55} {77} {105} {115} {116} {117} {119} .



Sedative:
Daytime—Oral, 15 to 30 mg three or four times a day {07} {48} {55} {77} {105} {115} {116} {117} {119} .

Preoperative—Oral, 50 to 100 mg sixty to ninety minutes before surgery {07} {32} {48} {55} {77} {115} {116} {117} {119}.



Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients. {32} {48} {77} {115} {116}


Usual pediatric dose
Sedative-hypnotic


Hypnotic:
Dosage must be individualized by physician.



Sedative:
Daytime—Oral, 2 mg per kg of body weight or 60 mg per square meter of body surface three times a day {02} {04} {77} {105} .

Preoperative—Oral, 2 to 6 mg per kg of body weight, up to a maximum of 100 mg per dose {07} {48} {55} {77} {115} {116} {117} {119}.



Strength(s) usually available
U.S.—


30 mg per 5 mL (Rx) [Busodium] [Butalan] [Butisol (alcohol [by volume] 7%) (tartrazine)][Generic]{76}{77}{80}{82}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.
   • Keep container tightly closed.

Note: Controlled substance in the U.S.



BUTABARBITAL SODIUM TABLETS USP

Usual adult dose
See Butabarbital Sodium Elixir USP .

Usual pediatric dose
See Butabarbital Sodium Elixir USP .

Strength(s) usually available
U.S.—


15 mg (Rx) [Busodium] [Butisol (scored)][Generic]


30 mg (Rx) [Busodium] [Butisol (scored) (tartrazine)] [Sarisol No. 2][Generic]


50 mg (Rx) [Butisol (scored) (tartrazine)]


100 mg (Rx) [Busodium] [Butisol (scored)][Generic]
{76}{77}{80}{81}{82}{83}
Canada—


15 mg (Rx) [Butisol (scored) (sodium 2 mg)]


30 mg (Rx) [Butisol (scored) (sodium 3 mg) (tartrazine)]


100 mg (Rx) [Butisol (scored) (sodium 10 mg)]
{105}{106}
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.



MEPHOBARBITAL

Summary of Differences


Category:
Indicated only as an anticonvulsant.



Pharmacology/pharmacokinetics:


Biotransformation—
About 75% of a single dose metabolized to phenobarbital in 24 hours.



Long-acting barbiturate—
Onset of action: 60 minutes or longer.

Duration of action: 10 to 12 hours.




Patient consultation:
Compliance with therapy when used as an anticonvulsant.



Additional Dosing Information
See also General Dosing Information.
In epilepsy

   • Therapy with mephobarbital should begin with small doses, the dosage being gradually increased over a period of 4 to 5 days until the optimum dosage is determined {49} {84}.
   • When used to replace another anticonvulsant, the dosage of mephobarbital should be gradually increased while the dosage of the other medication is maintained initially and then gradually decreased in order to maintain seizure control {49} {84}.
   • Mephobarbital may be alternated with phenobarbital therapy {49}.
   • When used in conjunction with phenytoin, the dose of phenytoin may need to be reduced, but the full dose of mephobarbital may be given {49} {84}.
   • Mephobarbital should be withdrawn slowly in order to avoid precipitating seizures or status epilepticus. When the dosage is to be reduced to a maintenance level or discontinued, the amount should be reduced over a period of 4 to 5 days or possibly longer. {49} {84}


Oral Dosage Forms

MEPHOBARBITAL TABLETS USP

Usual adult dose
Anticonvulsant
Oral, 200 mg at bedtime to 600 mg a day in divided doses {08} {33} {49} {55} {84} {107} {117} {119}.

Sedative-hypnotic
Sedative: Daytime—Oral, 32 to 100 mg three or four times a day {08} {49} {55} {84} {107} {117} {119}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients. {84}


Usual pediatric dose
Anticonvulsant
Children up to 5 years of age: Oral, 16 to 32 mg three or four times a day {08} {33} {49} {84} {107} {117} .

Children 5 years of age and over: Oral, 32 to 64 mg three or four times a day {08} {33} {49} {84} {107}.

Sedative-hypnotic
Sedative: Daytime—Oral, 16 to 32 mg three or four times a day {08} {84} {107}.


Strength(s) usually available
U.S.—


32 mg (Rx) [Mebaral (scored) (lactose) (starch) (stearic acid) (talc)]


50 mg (Rx) [Mebaral (lactose) (starch) (stearic acid) (talc)]


100 mg (Rx) [Mebaral (lactose) (starch) (stearic acid) (talc)]
{84}{85}
Canada—


30 mg (Rx) [Mebaral (lactose 65 mg)]{107}


100 mg (Rx) [Mebaral (lactose 59 mg)]{107}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.



METHARBITAL

Summary of Differences


Category:
Indicated only as an anticonvulsant.



Pharmacology/pharmacokinetics:


Biotransformation—
Metabolized to barbital.



Long-acting barbiturate—
Onset of action: 60 minutes or longer.

Duration of action: 10 to 12 hours.




Patient consultation:
Compliance with therapy.



Additional Dosing Information
See also General Dosing Information.

Metharbital should be withdrawn gradually in order to avoid the possibility of precipitating seizures or status epilepticus {50}.

When used to replace or supplement other anticonvulsant therapy, the dosage of metharbital should be gradually increased while the dosage of the other medication is maintained initially and then gradually decreased in order to maintain seizure control {50}.


Oral Dosage Forms

METHARBITAL TABLETS

Usual adult dose
Anticonvulsant
Oral, initially 100 mg one to three times a day, the dosage being increased up to 800 mg per day, if necessary {09} {34} {50} {55} {86} {117} {119}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Anticonvulsant
Oral, 50 mg one to three times a day; or 5 to 15 mg per kg of body weight per day in divided doses {09} {34} {50}.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—
Not commercially available.

In other countries—


100 mg [Gemonil (scored) (lactose)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.


PENTOBARBITAL

Summary of Differences


Category:
Parenteral pentobarbital also may be indicated as an anticonvulsant.



Indications:
Parenteral pentobarbital also used to protect brain from ischemia and increased intracranial pressure that follow stroke and head trauma.



Pharmacology/pharmacokinetics:


Short-acting barbiturate—
Onset of action: 10 to 15 minutes.

Duration of action: 3 to 4 hours.



Protein binding—
Moderate to high.




Additional Dosing Information
See also General Dosing Information.

When administered during labor, doses greater than 200 mg may cause respiratory depression in the newborn.

For parenteral dosage forms only
The injection is for intramuscular or intravenous use only; it is not recommended for subcutaneous administration {36} {52} {92}.

Intravenous injections should be made slowly, not to exceed 50 mg per minute, to avoid adverse respiratory and circulatory reactions {36} {52} {92}.


Oral Dosage Forms

PENTOBARBITAL ELIXIR USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Oral, 100 mg (pentobarbital sodium) at bedtime {10} {51} {55} {90} {117} {119}.



Sedative:
Daytime—Oral, 20 mg (pentobarbital sodium) three or four times a day {02} {04} {55} {117} {119}.



Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients. {90}


Usual pediatric dose
Sedative-hypnotic


Hypnotic:
Dosage must be individualized by physician {51} {90}.



Sedative:
Daytime—Oral, 2 to 6 mg (pentobarbital sodium) per kg of body weight per day {113}.

Preoperative—Oral, 2 to 6 mg (pentobarbital sodium) per kg of body weight, up to a maximum of 100 mg per dose {10} {51} {55} {90} {117} {119}.



Strength(s) usually available
U.S.—


20 mg of pentobarbital sodium (18.2 mg of pentobarbital) per 5 mL (Rx) [Nembutal (alcohol 18%)]{88}{89}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.
   • Keep container tightly closed.

Note: Controlled substance in the U.S.



PENTOBARBITAL SODIUM CAPSULES USP

Usual adult dose
Sedative-hypnotic
Hypnotic: Oral, 100 mg at bedtime {10} {35} {51} {55} {90} {108}.

Sedative: Preoperative—Oral, 100 mg {10} {35} {90} {108}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients. {35} {51} {90}


Usual pediatric dose
Sedative-hypnotic
Hypnotic: Dosage must be individualized by physician {10} {51} {90}.

Sedative: Preoperative—Oral, 2 to 6 mg per kg of body weight, up to a maximum of 100 mg per dose {10} {51} {55} {90} {117} {119}.


Strength(s) usually available
U.S.—


50 mg (Rx) [Nembutal][Generic]


100 mg (Rx) [Nembutal (tartrazine)][Generic]
{89}{90}{91}
Canada—


100 mg (Rx) [Nembutal (tartrazine)] [Novopentobarb]{108}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.




Parenteral Dosage Forms

PENTOBARBITAL SODIUM INJECTION USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Intramuscular, 150 to 200 mg {01} {10} {36} {37} {52} {55} {92} {117} {119}.

Intravenous, 100 mg initially; after one minute, additional small doses may be administered at one-minute intervals, if necessary, up to a total of 500 mg {01} {10} {36} {37} {52} {55} {92} {108} {117} {119}.



Sedative:
Preoperative—Intramuscular, 150 to 200 mg {04} {113}.


Anticonvulsant
Intravenous, 100 mg initially; after one minute, additional small doses may be administered at one-minute intervals, if necessary, up to a total of 500 mg {10} {36} {37} {52} {92}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients. {92}


Usual pediatric dose
Sedative-hypnotic


Hypnotic:
Intramuscular, 2 to 6 mg per kg of body weight, up to a maximum of 100 mg per dose {10} {36} {52} {92}.

Intravenous, 50 mg initially; after one minute, additional small doses may be administered at one-minute intervals, if necessary, until desired effect is obtained {02} {10} {108}.



Sedative:
Preoperative—Intramuscular, 2 to 6 mg per kg of body weight, up to a maximum of 100 mg per dose {01} {10} {37} {167}.


Anticonvulsant
Intramuscular or intravenous, 50 mg initially; after one minute, additional small doses may be administered at one-minute intervals, if necessary, until desired effect is obtained {04} {10} {113}.


Strength(s) usually available
U.S.—


50 mg per mL (Rx) [Nembutal (alcohol 10%) (propylene glycol 40% v/v)][Generic]{89}{91}{92}

Canada—


50 mg per mL (Rx) [Nembutal (alcohol 10%) (propylene glycol 40%)]{108}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. {92}

Stability:
Do not use if solution is discolored or contains a precipitate {92}.

Note: Controlled substance in the U.S. and Canada.




Rectal Dosage Forms

PENTOBARBITAL SODIUM SUPPOSITORIES

Usual adult dose
Sedative-hypnotic


Hypnotic:
Rectal, 120 to 200 mg at bedtime {11} {38} {53} {93} {165}.



Sedative:
Daytime—Rectal, 30 mg two to four times a day {53} {93} {165}.



Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients. {93}


Usual pediatric dose
Sedative-hypnotic


Hypnotic:
Children up to 2 months of age: Dosage has not been established {11} {38} {53} {93} {165}.

Children 2 months to 1 year of age (4.5 to 9 kg): Rectal, 30 mg {11} {38} {53} {93} {165}.

Children 1 to 4 years of age (9 to 18 kg): Rectal, 30 or 60 mg {11} {38} {53} {93} {165}.

Children 5 to 12 years of age (18 to 36 kg): Rectal, 60 mg {11} {38} {53} {93} {165}.

Children 12 to 14 years of age (36 to 50 kg): Rectal, 60 or 120 mg {11} {38} {53} {93} {165}.



Sedative:


Daytime—
Rectal, 2 mg per kg of body weight or 60 mg per square meter of body surface three times a day {04} {53} {165}.



Preoperative—
Children up to 2 months of age: Dosage has not been established {01}.

Children 2 months to 1 year of age: Rectal, 30 mg {01} {117} {119} {165}.

Children 1 to 4 years of age: Rectal, 30 or 60 mg {01} {117} {119} {165}.

Children 5 to 12 years of age: Rectal, 60 mg {01} {117} {119} {165}.

Children 12 to 14 years of age: Rectal, 60 or 120 mg {117} {119}.




Strength(s) usually available
U.S.—


30 mg (Rx) [Nembutal (semisynthetic glycerides)]


60 mg (Rx) [Nembutal (semisynthetic glycerides)]


120 mg (Rx) [Nembutal (semisynthetic glycerides)]


200 mg (Rx) [Nembutal (semisynthetic glycerides)]
{89}{93}
Canada—


25 mg (Rx) [Nova Rectal (in a polyethylene glycol base)]{165}


50 mg (Rx) [Nova Rectal (in a polyethylene glycol base)]{165}

Packaging and storage:
Store between 2 and 15 °C (36 and 59 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • For rectal use only.
   • Avoid alcoholic beverages.
   • May cause drowsiness.
   • Refrigerate.

Note: Controlled substance in the U.S. and Canada.



PHENOBARBITAL

Summary of Differences


Category:
Also indicated as an anticonvulsant.

Oral and parenteral phenobarbital also used as an antihyperbilirubinemic; and has been used as an antitremor agent, although generally has been replaced by benzodiazepines and beta-adrenergic blockers.



Pharmacology/pharmacokinetics:


Distribution—
Distributed less rapidly than other barbiturates because it has lowest lipid solubility.



Time to peak effect—
Maximal CNS depression may not occur for 15 minutes or more after intravenous administration.



Long-acting barbiturate—
Onset of action: 60 minutes or longer.

Duration of action: 10 to 12 hours.



Protein binding—
Low to moderate.




Patient consultation:
Compliance with therapy when used as an anticonvulsant.



Additional Dosing Information
See also General Dosing Information.
In epilepsy

   • In children, higher-per-kg dosage of phenobarbital and most other anticonvulsants generally are required to achieve blood concentrations considered therapeutic.
   • Several weeks of phenobarbital therapy may be required to achieve maximum antiepilepsy effects.
   • Phenobarbital should be withdrawn slowly in order to avoid precipitating seizures or status epilepticus.
   • When phenobarbital is replaced by another anticonvulsant, the dosage of phenobarbital should be maintained initially and then reduced gradually while, at the same time, the dosage of the replacement medication is increased gradually in order to maintain seizure control.
   • When administered intravenously, phenobarbital sodium may require 15 minutes or more to attain peak concentrations in the brain; therefore, it is important to use the minimal dosage required and to wait for the anticonvulsant effect to develop before administering a second dose, in order to avoid the possibility of severe barbiturate-induced depression {55}.

For parenteral dosage forms only
Sterile phenobarbital sodium may be administered subcutaneously after reconstitution, but phenobarbital sodium injection is not recommended for subcutaneous use.

The rate of the intravenous injection should not exceed 60 mg per minute. Faster rates of administration may cause serious respiratory depression. {55} {117}

Following intravenous administration, up to 30 minutes may be required for maximum effect.

Bioequivalence information


For phenobarbital tablets
Bioavailability differences between generic products from different manufacturers have been reported in the past {183} {184}. However, no controlled studies systematically comparing the large number of tablets commercially available from different manufacturers have been conducted. In two studies published in 1979 and 1984 comparing phenobarbital tablets from different manufacturers in male volunteers, there were no significant differences in mean peak plasma concentrations (C max) or relative area under the plasma concentration-time curve (AUC); however, statistically significant delays in reaching time of peak concentration (t max) were demonstrated among products {183} {184}. In response to the potential problem of bio-inequivalence, official dissolution standards were changed {185}, and problems have not been documented in the years following establishment of these standards {185}. The current standard excludes slow-dissolving tablets {185}.



Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

PHENOBARBITAL CAPSULES

Usual adult dose
Anticonvulsant
Oral, 60 to 250 mg (base) per day, as a single dose or in divided doses {01} {39} {55} {95} {117} {119} .

Sedative-hypnotic
Hypnotic: Oral, 100 to 320 mg (base) at bedtime {01} {12} {39} {55} {95} {117} {119} .

Sedative: Daytime—Oral, 30 to 120 mg (base) in two or three divided doses a day {01} {12} {55} {95} {117} {119} .

[Antihyperbilirubinemic]1
Oral, 30 to 60 mg (base) three times a day {04} {113}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Anticonvulsant
Oral, 1 to 6 mg (base) per kg of body weight per day, as a single dose or in divided doses {12} {167}.

Sedative-hypnotic


Hypnotic:
Dosage must be individualized by physician.



Sedative:
Daytime—Oral, 2 mg (base) per kg of body weight or 60 mg per square meter of body surface three times a day {12} {95} {113}.

Preoperative—Oral, 1 to 3 mg (base) per kg of body weight {04} {39} {55} {117} {119}.


[Antihyperbilirubinemic]1
Neonates: Oral, 5 to 10 mg (base) per kg of body weight per day for the first few days after birth {13} {113} .

Children up to 12 years of age: Oral, 1 to 4 mg (base) per kg of body weight three times a day {04} {113}.


Strength(s) usually available
U.S.—


15 mg (Rx) [Solfoton]{94}{94a}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S.



PHENOBARBITAL ELIXIR USP

Usual adult dose
See Phenobarbital Capsules .

Usual pediatric dose
See Phenobarbital Capsules .

Strength(s) usually available
U.S.—


20 mg per 5 mL (Rx)[Generic]{95}{96}

Canada—


20 mg per 5 mL (Rx) [Ancalixir]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.
   • Keep container tightly closed.

Note: Controlled substance in the U.S. and Canada.



PHENOBARBITAL TABLETS USP

Note: Bioavailability differences between products from different manufacturers have been reported in the past {183} {184}. However, no controlled studies systematically comparing the large number of tablets commercially available from different manufacturers have been conducted. In two studies published in 1979 and 1984 comparing phenobarbital tablets from different manufacturers in male volunteers, there were no significant differences in mean peak plasma concentrations (C max) or relative area under the plasma concentration-time curve (AUC); however, statistically significant delays in reaching time of peak concentration (T max) were demonstrated among products {183} {184}. In response to the potential problem of bio-inequivalence, official dissolution standards were changed {185}, and problems have not been documented in the years following establishment of these standards {185}. The current standard excludes slow-dissolving tablets {185}.


Usual adult dose
See Phenobarbital Capsules .

Usual pediatric dose
See Phenobarbital Capsules .

Strength(s) usually available
U.S.—


8 mg (Rx)[Generic]


15 mg (Rx) [Barbita] [Solfoton][Generic]


30 mg (Rx)[Generic]


60 mg (Rx)[Generic]


100 mg (Rx)[Generic]
{94}{95}{95a}{96}
Canada—


15 mg (Rx)[Generic]


30 mg (Rx)[Generic]


60 mg (Rx)[Generic]


100 mg (Rx)[Generic]
{109}{109a}
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.




Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

PHENOBARBITAL SODIUM INJECTION USP

Usual adult dose
Anticonvulsant
Intravenous, 100 to 320 mg, repeated if necessary up to a total dose of 600 mg during a twenty-four-hour period {16} {39} {117} {119}.

Status epilepticus: Intravenous (slow), 10 to 20 mg per kg of body weight, repeated if necessary {16} {39} {167}.

Sedative-hypnotic


Hypnotic:
Intramuscular or intravenous, 100 to 325 mg {15} {55} {113}.



Sedative:
Daytime—Intramuscular or intravenous, 30 to 120 mg a day in two or three divided doses {04} {55} {117} {119}.

Preoperative—Intramuscular, 130 to 200 mg sixty to ninety minutes before surgery {15} {55} {113} {117} {119}.



Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Anticonvulsant
Initial: Intravenous, 10 to 20 mg per kg of body weight as a single loading dose {16} {55} {117}.

Maintenance: Intravenous, 1 to 6 mg per kg of body weight per day {16} {55} {117} {119}.

Status epilepticus: Intravenous, 15 to 20 mg per kg of body weight, administered over a period of ten to fifteen minutes {16} {55} {117} {119} {167}.

Sedative-hypnotic
Hypnotic: Dosage must be individualized.

Sedative: Preoperative—Intramuscular or intravenous, 1 to 3 mg per kg of body weight, sixty to ninety minutes prior to surgery {04} {55} {113} {117} {119}.

[Antihyperbilirubinemic]1
Intramuscular, 5 to 10 mg per kg of body weight per day for the first few days after birth {04} {13} {113}.


Strength(s) usually available
U.S.—


30 mg per mL (Rx)[Generic]


60 mg per mL (Rx)[Generic]


65 mg per mL (Rx)[Generic]


130 mg per mL (Rx) [Luminal (alcohol 10%) (propylene glycol 67.8% by volume)][Generic]
{97}{98}
Canada—


30 mg per mL (Rx)[Generic]{110}


120 mg per mL (Rx)[Generic]{110}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Stability:
Do not use if solution is discolored or contains a precipitate.

Note: Controlled substance in the U.S. and Canada.



PHENOBARBITAL SODIUM STERILE USP

Usual adult dose
Anticonvulsant
Intravenous, 100 to 320 mg, repeated if necessary up to a total dose of 600 mg during a twenty-four-hour period {16} {117} {118}.

Status epilepticus: Intravenous (slow), 10 to 20 mg per kg of body weight, repeated if necessary {16} {167}.

Sedative-hypnotic


Hypnotic:
Intramuscular, intravenous, or subcutaneous, 100 to 325 mg {15} {119}.



Sedative:
Daytime—Intramuscular, intravenous, or subcutaneous, 30 to 120 mg a day in two or three divided doses {04} {117} {119}.

Preoperative—Intramuscular, 130 to 200 mg sixty to ninety minutes before surgery {15} {117} {119}.



Note: Geriatric and debilitated patients may react to usual doses of barbiturates with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Anticonvulsant
Initial: Intravenous, 10 to 20 mg per kg of body weight as a single loading dose {16} {117}.

Maintenance: Intravenous, 1 to 6 mg per kg of body weight per day {16}.

Status epilepticus: Intravenous, 15 to 20 mg per kg of body weight, administered over a period of ten to fifteen minutes {16} {167}.

Sedative-hypnotic
Hypnotic: Dosage must be individualized.

Sedative: Preoperative—Intramuscular, 1 to 3 mg per kg of body weight {04}.

[Antihyperbilirubinemic]1
Intramuscular, 5 to 10 mg per kg of body weight per day for the first few days after birth {04} {13} {113}.


Size(s) usually available:
U.S.—


120 mg (Rx)[Generic]{98}

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
Solutions of phenobarbital sodium for subcutaneous or intramuscular injection may be prepared by dissolving 120 mg of anhydrous phenobarbital sodium powder in 1 mL of sterile water for injection. For intravenous use, 120 mg of anhydrous phenobarbital sodium powder should be dissolved in 3 mL of sterile water for injection. When solutions are prepared, the sterile water for injection should be introduced slowly into the vial by means of a sterile syringe. Several minutes may be required for the medication to dissolve completely; solution should not be injected if it has not become clear after 5 minutes. {118}

Stability:
After reconstitution, solution should be used within thirty minutes since phenobarbital hydrolyzes in solution or upon exposure to air. Solution should not be used if it does not become absolutely clear within 5 minutes after reconstitution or if a precipitate forms after the solution clears.

Note: Controlled substance in the U.S.



SECOBARBITAL

Summary of Differences


Category:
Parenteral secobarbital also may be indicated as an anticonvulsant (in tetanus).



Pharmacology/pharmacokinetics:


Distribution—
Distributed more rapidly than other barbiturates because it has highest lipid solubility.



Short-acting barbiturate—
Onset of action: 10 to 15 minutes.

Duration of action: 3 to 4 hours.



Protein binding—
Moderate to high.




Additional Dosing Information
See also General Dosing Information.

For parenteral dosage forms only
The rate of the intravenous injection should not exceed 50 mg per 15-second period. Faster rates of administration may cause respiratory depression or apnea, laryngospasm, or vasodilation with fall in blood pressure. {05} {58} {117}

For rectal dosage forms only
To prepare a solution for rectal administration, dilute the commercially available 5% secobarbital sodium injection with lukewarm tap water to a concentration of 10 to 15 mg per mL (1 to 1.5%).


Oral Dosage Forms

SECOBARBITAL SODIUM CAPSULES USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Oral, 100 mg at bedtime {17} {40} {55} {99a} {117} {119}.



Sedative:
Daytime—Oral, 30 to 50 mg three or four times a day {17} {113}.

Preoperative—Oral, 200 to 300 mg one to two hours before surgery {17} {40} {55} {99a} {117} {119}.



Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Sedative-hypnotic


Sedative:
Daytime—Oral, 2 mg per kg of body weight or 60 mg per square meter of body surface three times a day {02} {04} {13} {168}.

Preoperative—Oral, 2 to 6 mg per kg of body weight, up to a maximum of 100 mg per dose, one to two hours before surgery {01} {17} {40} {55} {99a} {117} {119}.



Strength(s) usually available
U.S.—


100 mg (Rx) [Seconal][Generic]{99}

Canada—


50 mg (Rx) [Seconal]{111}


100 mg (Rx) [Novosecobarb] [Seconal]{111}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.




Parenteral Dosage Forms

SECOBARBITAL SODIUM INJECTION USP

Usual adult dose
Sedative-hypnotic


Hypnotic:
Intramuscular, 100 to 200 mg {18} {40} {41} {55} {117} {119}.

Intravenous, 50 to 250 mg {18} {40} {41} {55} {117} {119}.



Sedative:
Dentistry—Intramuscular, 1.1 to 2.2 mg per kg of body weight ten to fifteen minutes before procedure {18} {40} {55} {117} {119}.

Nerve block—Intravenous, 100 to 150 mg {18} {40} {41} {55} {58} {117} {119}.


Anticonvulsant (in tetanus)
Intramuscular or intravenous, 5.5 mg per kg of body weight, repeated every three to four hours as needed {01} {40} {55} {58} {117} {119}.


Note: Geriatric and debilitated patients may react to usual doses of barbiturates with excitement, confusion, or mental depression. Lower doses may be required in these patients.


Usual pediatric dose
Sedative-hypnotic


Hypnotic:


Intramuscular—
3 to 5 mg per kg of body weight or 125 mg per square meter of body surface, up to a maximum of 100 mg per dose {04} {19} {113} {168} .



Rectal, the following doses as a 1 to 1.5% solution—
Children weighing up to 40 kg: 5 mg per kg of body weight {04} {40} {58} {113}.

Children weighing 40 kg and over: 4 mg per kg of body weight {04} {40} {58} {113}.




Sedative:


Preoperative—
Intramuscular, 4 to 5 mg per kg of body weight {18} {41} {55} {117}.



Anticonvulsant (in tetanus)
Intramuscular or intravenous, 3 to 5 mg per kg of body weight or 125 mg per square meter of body surface per dose {19}.


Strength(s) usually available
U.S.—


50 mg per mL (Rx)[Generic]{99}{99a}

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). Protect from light.

Preparation of dosage form:
Secobarbital sodium injection may be administered in a concentration of 50 mg per mL or it may be diluted with sterile water for injection, 0.9% sodium chloride injection, or Ringer's injection {51}.

Stability:
Do not use if solution is discolored or contains a precipitate.

Note: Controlled substance in the U.S.



SECOBARBITAL AND AMOBARBITAL


Oral Dosage Forms

SECOBARBITAL SODIUM AND AMOBARBITAL SODIUM CAPSULES USP

Usual adult dose
Sedative-hypnotic
Oral, 1 capsule at bedtime or one hour preoperatively {20} {42} {59} {101} {112} {121}.


Note: Geriatric and debilitated patients may react to usual doses with excitement, confusion, or mental depression. Lower doses may be required in these patients. {121}


Usual pediatric dose
Dosage has not been established {121}.

Strength(s) usually available
U.S.—


50 mg of secobarbital and 50 mg of amobarbital (Rx) [Tuinal]


100 mg of secobarbital and 100 mg of amobarbital (Rx) [Tuinal]
{101}{102}
Canada—


50 mg of secobarbital and 50 mg of amobarbital (Rx) [Tuinal]{112}


100 mg of secobarbital and 100 mg of amobarbital (Rx) [Tuinal]{112}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.

Note: Controlled substance in the U.S. and Canada.




Revised: 08/15/1995



References
  1. FDA Class Labeling Guidelines for Single-Entity Barbiturates, 11/80.
  1. AMA-DE 5th ed., pp 201-204.
  1. Amytal (oral) PI, Lilly, Rev 10/79, Rec 4/80.
  1. AHFS 28:24, 1986.
  1. Amytal (parenteral) PI, Lilly, Rev 10/79, Rec 4/80.
  1. Alurate PI, Roche, PDR 1986, p 1472.
  1. Butisol PI, Wallace, PDR 1986, p 1872.
  1. Mebaral PI, Winthrop-Breon, PDR 1986, p 1922.
  1. Gemonil PI, Abbott, PDR 1986, pp 525-526.
  1. Nembutal PI, Abbott, PDR 1986, p 535.
  1. Nembutal Rectal PI, Abbott, PDR 1986, p 537.
  1. Phenobarbital (oral) PI, Wyeth, Rev 3/85.
  1. Pediatric Drug Handbook, Shirkey, 1977-79.
  1. F&C, 4/83, p 276.
  1. Phenobarbital (parenteral) PI, Wyeth, Rev 3/83.
  1. Panel comments.
  1. Seconal PI, Lilly, PDR 1986, p. 1069.
  1. Secobarbital PI, Wyeth, Rev 10/85.
  1. Pediatric Dosage Handbook, APHA, 1980.
  1. Tuinal PI, Lilly, PDR 1986, p 1070.
  1. Lotusate PI, Winthrop-Breon, Rev 5/84.
  1. USAN 1986.
  1. USP/NF XXI.
  1. Manufacturer comment, 6/27/85.
  1. Manufacturer comment.
  1. Panelist comment.
  1. Mexiletine monograph.
  1. Amytal Tabs PI, Lilly, Rev 8/85, Rec 5/87.
  1. Amytal Caps PI, Lilly, Rev 1/86, Rec 5/87.
  1. Amytal Na, Sterile, PI, Lilly, Rev 8/85, Rec 5/87.
  1. Alurate Elixir, Roche, PDR 1987, p 1642.
  1. Butisol PI, Wallace, Rev 2/85, Rec 5/87.
  1. Mebaral PI, Winthrop-Breon, Rev 6/85, Rec 4/87.
  1. Gemonil PI, Abbott, Rev 10/85, Rec 5/87.
  1. Nembutal Caps, Abbott, PDR 1987, p 535.
  1. Nembutal Inj PI, Abbott, Rev 11/86, Rec 5/87.
  1. Pentobarbital Na Inj PI, Wyeth, Rev 10/86, Rec 5/87.
  1. Nembutal Na Supp PI, Abbott, Rev 8/85, Rec 5/87.
  1. Phenobarbital Inj PI, Lederle, Rev 1/86, Rec 5/87.
  1. Seconal PI, Lilly, Rev 8/86, Rec 5/87.
  1. Secobarb Inj PI, Wyeth, Rev 10/86, Rec 5/87.
  1. Tuinal PI, Lilly, Rev 2/86, Rec 5/87.
  1. Lotusate PI, Winthrop-Breon, Rev 7/85, Rec 4/87.
  1. Reviewer comment, 3/9/87, Rec 5/19/87.
  1. USP DI 1988.
  1. Amytal (Oral) PI, Abbott, Rev 8/85, Rec 5/87.
  1. Amytal (Par) PI, Abbott, Rev 8/85, Rec 5/87.
  1. Butisol PI, Wallace, Rev 2/85, Rec 5/87.
  1. PDR 1988, p 2239; & Mebaral PI, Winthrop, Rev 6/85, Rec 4/87.
  1. PDR 1988, p 529, Gemonil, Abbott.
  1. PDR 1988, p 536, Nembutal Capsules, Abbott.
  1. PDR 1988, p 538, Nembutal Sodium Inj, Abbott.
  1. PDR 1988, p 540, Nembutal Sodium Supp, Abbott.
  1. Solfoton PI, Poythress, Rev 9/81, Rec 4/87.
  1. Phenobarbital Tablets PI, Lederle, Rev 1/86, Rec 5/87.
  1. Luminal Inj PI, Lilly, Rev 3/84, Rec 4/87.
  1. Seconal (Oral) PI, Lilly, Rev 8/86, Rec 5/87.
  1. Seconal (Par) PI, Lilly, Rev 5/82, Rec 5/87.
  1. Tuinal PI, Lilly, Rev 2/86, Rec 5/87.
  1. Lotusate PI, Winthrop, Rev 7/85, Rec 4/87.
  1. Anticonvulsants, Succinimide (Sys) monograph, DI 89.
  1. Panelist comment.
  1. Clin Pharmacol Ther 18:733, 1975, Cereghino J J et. al.
  1. Neurology 1987, Dreifuss, F.
  1. AHFS 1988, 28:24.04.
  1. G & G, 7th ed, p 352.
  1. Drug Tx, Avery, 2nd ed.
  1. Panelist comment.
  1. Amytal Tablets PI, Lilly, Rev 2/18/87, Rec 1/89.
  1. Amytal Capsules PI, Lilly, Rev 1/14/86, Rec 1/89.
  1. Redbook 1989, p 150.
  1. Redbook 1989, p 145.
  1. PDR 1989, Alurate (Winthrop), Rev 6/88, p 1717.
  1. Redbook 1989, p 135.
  1. Bluebook 1987-88, p 46.
  1. F & C, Rev 12/86, p 277a.
  1. Bluebook 1987-88, p 119.
  1. Bluebook 1987-88, p 200.
  1. Butisol PI, Wallace, Rev 2/85, Rec 11/88.
  1. Redbook 1989, p 199.
  1. PDR 1989, Butisol (Wallace), p 2196.
  1. Redbook 1989, p 201.
  1. Redbook 1989, p 626.
  1. Redbook 1989, pp 199, 200.
  1. Generic Butabarbital Sodium Tablets PI, West-Ward, Rev 1/88, Rec 3/89.
  1. PDR 1989, Mebaral (Winthrop), p 2258.
  1. Redbook 1989, p 458.
  1. PDR 1989, p 531.
  1. Redbook 1989, p 349.
  1. F & C, 12/86, p 280.
  1. Redbook 1989, p 501.
  1. PDR 1989, Nembutal Capsules (Abbott), p 539.
  1. Redbook 1989, p 547.
  1. PDR 1989, Nembutal Injection (Abbott), p 542.
  1. PDR 1989, Nembutal Supp (Abbott), p 544.
  1. Redbook 1989, p 645.
  1. Bluebook 1987-1988, p 527.
  1. Generic Phenobarbital Elixir & Tablets PI, Lilly, Rev 8/25/88, Rec 1/89.
  1. Redbook 1989, p 172.
  1. Redbook 1989, p 555.
  1. Redbook 1989, p 447.
  1. Redbook 1989, p 556.
  1. Redbook 1989, p 629.
  1. Seconal Sodium PI, Lilly, Rev 5/82, Rec 5/87.
  1. Bluebook 1987-88, p 517.
  1. Tuinal PI, Lilly, Rev 2/24/86, Rec 1/89.
  1. Redbook 1989, p 709.
  1. Redbook 1989, p 445.
  1. PDR 1989, p 2253.
  1. CPS 1988, p 46.
  1. CPS 1988, Rev 1983, p 125.
  1. CPS 1988, Rev 1987, p 230.
  1. CPS 1988, Rev 1988, p 528.
  1. CPS 1988, p 595.
  1. CPS 1988, p 364.
  1. CPS 1988, p 714.
  1. CPS 1988, p 506.
  1. CPS 1988, p 835.
  1. CPS 1988, p 958.
  1. AHFS 28:24
  1. Amytal Sodium, Sterile, PI (Lilly), Rev 2/18/87, Rec 1/89.
  1. Butisol Sodium Tablets & Elixir PI (Wallace), Rev 2/85, Rec 11/88.
  1. Generic Butabarbital Sodium Tablets PI (West-Ward), Rev 1/88, Rec 3/89.
  1. Generic Phenobarbital Tablets PI (Danbury), Rev 3/86, Rec 1/89.
  1. Generic Sterile Phenobarbital Sodium PI (Lilly), Rev 10/4/85, Rec 1/89.
  1. Generic Phenobarbital Tablets PI (Lederle), Rev 1/86, Rec 4/24/89.
  1. Lotusate PI(Winthrop), Rev 3/87, Rec 2/89.
  1. Tuinal PI (Lilly), Rev 2/24/86, Rec 1/89.
  1. Acetaminophen (Sys) monograph, USP DI 1989, p 2.
  1. Adrenocorticoids (Sys—Mineralocorticoid Effects), USP DI 1989, p 50.
  1. Adrenocorticoids/Corticotropin (Sys—Glucocorticoid Effects), USP DI 1989, p 87.
  1. Cyclosporine (Sys), USP DI 1989, p 963.
  1. Dacarbazine (Sys), USP DI 1989, p 971.
  1. Digitalis Glycosides (Sys), USP DI 1989, p 1027.
  1. Thyroid Hormones (Sys), USP DI 1989, p 2333.
  1. Quinidine (Sys), USP DI 1989, p 2085.
  1. Amphetamines (Sys), USP DI 1989, p 158.
  1. Anesthetics, Inhalation (Sys), USP DI 1989, p 233.
  1. Anticoagulants (Sys), USP DI 1989, p 287.
  1. Anticonvulsants, Hydantoin (Sys), USP DI 1989, p 298.
  1. Anticonvulsants, Succinimide (Sys), USP DI 1989, p 306.
  1. Antidepressants, Tricyclic, USP DI 1989, p 318.
  1. Ascorbic Acid (Sys), USP DI 1989, p 480.
  1. Ca Channel Blocking Agents (Sys), USP DI 1989, p 681.
  1. Carbonic Anhydrase Inhibitors (Sys), USP DI 1989, p 715.
  1. Estrogens & Progestins (Sys), USP DI 1989, p 1173.
  1. Cyclophosphamide (Sys), USP DI 1989, p 953.
  1. Disopyramide (Sys), USP DI 1989, p 1062.
  1. Guanadrel (Sys), USP DI 1989, p 1281.
  1. Guanethidine (Sys), USP DI 1989, p 1284.
  1. Valproic Acid (Sys), USP DI 1989, p 2392.
  1. Tetracyclines (Sys), USP DI 1989, p 2288.
  1. Anti-inflammatory Analgesics, Nonsteroidal (Sys), USP DI 1989, p 419.
  1. Anti-inflammatory Analgesics, Nonsteroidal (Sys), USP DI 1989, pp 415, 417.
  1. Griseofulvin (Sys), USP DI 1989, p 1271.
  1. Haloperidol (Sys), USP DI 1989, p 1293.
  1. Ketamine (Sys), USP DI 1989, p 1453.
  1. Leucovorin (Sys), USP DI 1989, p 1501.
  1. Thyroid Hormones (Sys), USP DI 1989, p 2333.
  1. Loxapine (Sys), USP DI 1989, p 1542.
  1. Phenothiazines (Sys), USP DI 1989, p 1936.
  1. Thioxanthenes (Sys), USP DI 1989, p 2320.
  1. Maprotiline (Sys), USP DI 1989, p 1555.
  1. Methylphenidate (Sys), USP DI 1989, p 1636.
  1. Mexiletine (Sys), USP DI 1989, p 1658.
  1. MAOIs (Sys), USP DI 1989, p 310.
  1. Posterior Pituitary (Sys), USP DI 1989, p 2001.
  1. Primidone (Sys), USP DI 1989, p 2024.
  1. Vitamin D (Sys), USP DI 1989, p 2423.
  1. Bronchodilators, Xanthine-derivative (Sys), USP DI 1989, p 625.
  1. CPS 1988, Amytal, p 41.
  1. CPS 1988, Pentobarb Supp, p 628.
  1. Carbamazepine (Sys), USP DI 1989, p 702.
  1. Problems in Ped Drug Therapy, 2nd ed, p 566.
  1. AMA-DE 6th ed, p 105.
  1. Metyrapone (Systemic), USP DI 1991
  1. Baciewicz AM, Self TH. Rifampin drug interactions. Arch Intern Med. 8/84; 144:1667-71.
  1. Inoue E. Clinical implications of anticonvulsant-induced folate deficiency. Clin Pharm (Jul-Aug) 1982; 1: 372-3.
  1. Levy R et al, eds. Antiepileptic Drugs. 3rd ed. New York: Raven Press Ltd, 1989: 122; 267-378; 420.
  1. Pisani F, Perucca E and DiPerri R. Clinically relevant antiepileptic drug interactions. J Int Med Res 1990; 18: 1-15.
  1. Facts and Comparisons Drug Information Facts, 1983, p 190.
  1. Shinn and Shrewsbury; Evaluation of Drug Interactions, 3rd ed, pp.141, 358.
  1. Package insert, Flagyl IV and IV RTU (Searle), Rev 3/88, Rec 3/89.
  1. Mead PB, et al. Possible alteration of metronidazole metabolism by phenobarbital. N Eng J Med. 6/17/82; 306:1490.
  1. Gupte S. Phenobarbital and metabolism of metronidazole. N Eng J Med. 1983; 308(9):529.
  1. Hansten PD and Horn JR. Drug Interactions. 6th ed. Philadelphia: Lea and Febiger, 1989.
  1. Facts and Comparisons Drug Information Facts. Jan 1990.
  1. Mattson RH, Cramer JA, Darney PD, and Naftolin F. Use of oral contraceptives by women with epilepsy. JAMA (Jul 11) 1986; 256 (2): 238-240.
  1. Manufacturer comment on Belladonna Alkaloids and Barbiturates ballot, 2/91.
  1. Sylvestri MF, Ueda CT. In vitro and in vivo characteristics of some commercial phenobarbital tablets. Int J Clin Pharmacol Biopharm 1979 Dec; 17(12): 492-7.
  1. Meyer MC, Straughn AB, Raghow G, Schary WL, Rotenberg KS. Absorption of phenobarbital from tablets and elixir. J Pharm Sci 1984 Apr; 73(4): 485-8.
  1. Personal communication, Drug Standards Division, USP, 7/95.
Hide
(web2)