Drugs List

Therapeutic Indications

Uses

Epilepsy - except absence seizures
Status epilepticus

Contraindications

Acute porphyria
Breastfeeding
Severe hepatic disorder
Severe renal impairment
Severe respiratory depression

Precautions and Warnings

Children under 18 years
Debilitation
Elderly
Hepatic impairment
History of alcohol abuse
History of drug misuse
Hypothyroidism
Pregnancy
Renal impairment
Respiratory impairment

Advise ability to drive/operate machinery may be affected by side effects
Increased risk of osteomalacia; consider vitamin D supplement
Monitor for mental changes, suicidal depression and antisocial behaviour
Prolonged or excessive use may result in dependence
Advise patients/carers to seek medical advice if suicidal intent develops
Hyperactivity may be exacerbated
Rebound effect may occur after cessation of treatment
Tolerance may develop with continued use
May affect results of some laboratory tests
May affect thyroid function tests
Do not withdraw this drug suddenly
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Effect of hormonal contraceptive may be reduced
Neonate exposed in utero: Administer vitamin K at birth
Pregnancy: Administer vitamin K in the last few weeks of pregnancy
Pregnancy: Advise taking folate supplement as risk of neural tube defects

Long-term treatment with phenobarbital is associated with decreased bone mineral density, resulting in an increased risk of developing osteopenia, osteoporosis and fractures in at-risk patients (those immobilised for long periods or who have inadequate sun exposure or dietary calcium intake). Consider vitamin D supplementation for all at-risk patients on long-term treatment.

Pregnancy and Lactation

Pregnancy

Use phenobarbital sodium with caution in pregnancy.

Phenobarbital can cross the placenta. Studies have shown that phenobarbital can increase the risks of teratogenic effects when used in pregnancy. Briggs (2015) states that taking phenobarbital during pregnancy increases the risk of congenital defects such as a haemorrhage at birth or addiction. It can interfere with the uptake of folic acid, causing folic acid deficiency, therefore it is recommended to take folic acid supplements before conception and throughout pregnancy (Schaefer et al, 2015).
Phenobarbital is also known to induce enzymes that can lead to a reduction in vitamin K-dependent clotting factor which in turn can increase the risk of neonatal bleeding. Schaefer (2015) states that it is recommended for the mother to take prophylactic treatment with vitamin K1 before delivery and also administer vitamin K1 to the neonate immediately after delivery.

Briggs (2015) states that there is a greater risk to the mother if phenobarbital is not administered during pregnancy and seizure control is lost. The manufacturer suggests to only use phenobarbital during the first and third trimester if the potential benefits to the mother outweigh any potential risks to the foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Phenobarbital sodium is contraindicated in breastfeeding.

Phenobarbital is excreted in breast milk. Schaefer (2015) states that a breastfed infant could receive a significant amount of phenobarbital sodium if taken during breastfeeding, which can potentially result in sedating the infant. Hale (2014) and Briggs (2015) also support Schaefer stating that high concentrations of phenobarbital are likely to accumulate in the blood of the infant due to its long half life. It is advisable to monitor the infant if using phenobarbital during breastfeeding, especially if administering high doses due to the increased risk of sedating the infant (Briggs et al, 2015).

The Drugs and Lactation Database (LactMed) states using phenobarbital during breastfeeding can decrease withdrawal symptoms in the infant if they were exposed to the drug in the uterus. The manufacturer states breastfeeding is not recommended when administering phenobarbital sodium.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agranulocytosis
Allergic skin reactions
Aplastic anaemia
Ataxia
Behavioural disturbances
Cholestasis
Cognitive impairment
Confusion
Dependence
Depression
Disturbed vitamin D metabolism
Drowsiness
Dupuytren's contracture
Erythema multiforme
Excitement (paradoxical)
Exfoliative dermatitis
Fixed drug eruption
Folate deficiency
Hallucinations
Headache
Hepatitis
Hyperactivity
Hyperexcitability (children)
Hypocalcaemia
Hypophosphataemia
Hypoprothrombinaemia
Hypotension
Impaired memory
Insomnia
Irritability
Lethargy
Liver function disturbances
Macrocytic anaemia
Maculopapular rash
Megaloblastic anaemia
Mental status changes
Metabolic bone disease
Morbilliform eruption
Necrosis (injection site)
Nystagmus
Osteomalacia
Osteopenia
Osteoporosis
Paradoxical reactions
Photosensitivity
Purpura exfoliative dermatitis
Renal rickets
Respiratory depression
Restlessness
Scarlatiniform rash
Sedation
Stevens-Johnson syndrome
Thrombocytopenia
Toxic epidermal necrolysis
Withdrawal symptoms

Presentation

Parenteral formulations of phenobarbital sodium.

Drugs List

Therapeutic Indications

Uses

Epilepsy - except absence seizures
Status epilepticus

Dosage

Adults

Children

Contraindications

Acute porphyria
Breastfeeding
Severe hepatic disorder
Severe renal impairment
Severe respiratory depression

Precautions and Warnings

Children under 18 years
Debilitation
Elderly
Hepatic impairment
History of alcohol abuse
History of drug misuse
Hypothyroidism
Pregnancy
Renal impairment
Respiratory impairment

Advise ability to drive/operate machinery may be affected by side effects
Increased risk of osteomalacia; consider vitamin D supplement
Monitor for mental changes, suicidal depression and antisocial behaviour
Prolonged or excessive use may result in dependence
Advise patients/carers to seek medical advice if suicidal intent develops
Hyperactivity may be exacerbated
Rebound effect may occur after cessation of treatment
Tolerance may develop with continued use
May affect results of some laboratory tests
May affect thyroid function tests
Do not withdraw this drug suddenly
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Effect of hormonal contraceptive may be reduced
Neonate exposed in utero: Administer vitamin K at birth
Pregnancy: Administer vitamin K in the last few weeks of pregnancy
Pregnancy: Advise taking folate supplement as risk of neural tube defects

Long-term treatment with phenobarbital is associated with decreased bone mineral density, resulting in an increased risk of developing osteopenia, osteoporosis and fractures in at-risk patients (those immobilised for long periods or who have inadequate sun exposure or dietary calcium intake). Consider vitamin D supplementation for all at-risk patients on long-term treatment.

Pregnancy and Lactation

Pregnancy

Use phenobarbital sodium with caution in pregnancy.

Phenobarbital can cross the placenta. Studies have shown that phenobarbital can increase the risks of teratogenic effects when used in pregnancy. Briggs (2015) states that taking phenobarbital during pregnancy increases the risk of congenital defects such as a haemorrhage at birth or addiction. It can interfere with the uptake of folic acid, causing folic acid deficiency, therefore it is recommended to take folic acid supplements before conception and throughout pregnancy (Schaefer et al, 2015).
Phenobarbital is also known to induce enzymes that can lead to a reduction in vitamin K-dependent clotting factor which in turn can increase the risk of neonatal bleeding. Schaefer (2015) states that it is recommended for the mother to take prophylactic treatment with vitamin K1 before delivery and also administer vitamin K1 to the neonate immediately after delivery.

Briggs (2015) states that there is a greater risk to the mother if phenobarbital is not administered during pregnancy and seizure control is lost. The manufacturer suggests to only use phenobarbital during the first and third trimester if the potential benefits to the mother outweigh any potential risks to the foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Phenobarbital sodium is contraindicated in breastfeeding.

Phenobarbital is excreted in breast milk. Schaefer (2015) states that a breastfed infant could receive a significant amount of phenobarbital sodium if taken during breastfeeding, which can potentially result in sedating the infant. Hale (2014) and Briggs (2015) also support Schaefer stating that high concentrations of phenobarbital are likely to accumulate in the blood of the infant due to its long half life. It is advisable to monitor the infant if using phenobarbital during breastfeeding, especially if administering high doses due to the increased risk of sedating the infant (Briggs et al, 2015).

The Drugs and Lactation Database (LactMed) states using phenobarbital during breastfeeding can decrease withdrawal symptoms in the infant if they were exposed to the drug in the uterus. The manufacturer states breastfeeding is not recommended when administering phenobarbital sodium.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agranulocytosis
Allergic skin reactions
Aplastic anaemia
Ataxia
Behavioural disturbances
Cholestasis
Cognitive impairment
Confusion
Dependence
Depression
Disturbed vitamin D metabolism
Drowsiness
Dupuytren's contracture
Erythema multiforme
Excitement (paradoxical)
Exfoliative dermatitis
Fixed drug eruption
Folate deficiency
Hallucinations
Headache
Hepatitis
Hyperactivity
Hyperexcitability (children)
Hypocalcaemia
Hypophosphataemia
Hypoprothrombinaemia
Hypotension
Impaired memory
Insomnia
Irritability
Lethargy
Liver function disturbances
Macrocytic anaemia
Maculopapular rash
Megaloblastic anaemia
Mental status changes
Metabolic bone disease
Morbilliform eruption
Necrosis (injection site)
Nystagmus
Osteomalacia
Osteopenia
Osteoporosis
Paradoxical reactions
Photosensitivity
Purpura exfoliative dermatitis
Renal rickets
Respiratory depression
Restlessness
Scarlatiniform rash
Sedation
Stevens-Johnson syndrome
Thrombocytopenia
Toxic epidermal necrolysis
Withdrawal symptoms

Withdrawal Symptoms and Signs

Abrupt withdrawal should be avoided due to the risk of rebound seizures and withdrawal symptoms. A severe withdrawal syndrome may be precipitated including the following symptoms, rebound insomnia, anxiety, tremor, dizziness, nausea, fits and delirium.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Phenobarbital Sodium Injection BP 30 mg/ml. Martindale Pharma. Revised November 2012.

Summary of Product Characteristics: Phenobarbital Sodium Injection BP 60 mg/ml. Martindale Pharma. Revised November 2012.

Summary of Product Characteristics: Phenobarbital Sodium Injection BP 200 mg/ml. Martindale Pharma. Revised November 2012.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
<.Phenobarbital> Last revised: 07 September 2013
Last accessed: 08 March 2017

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14 September 2017