Phenobarbital Other names: Phenobarbitone

Concurrent administration with CNS depressants may lead to an additive CNS depressant effect.

The effect of phenobarbital can be reduced by concomitant use of the herbal remedy St John’s wort.

Phenobarbital increases the rate of metabolism reducing serum concentrations of corticosteroids.

Concurrent administration with alcohol may lead to an additive CNS depressant effect.

Phenobarbital increases the rate of metabolism reducing serum concentrations of anticoagulants.

Phenobarbital increases the rate of metabolism reducing serum concentrations of thyroid hormones. May increase requirements for thyroid hormones in hypothyroidism.

Reduced contraceptive effect.

Reduced contraceptive effect.

Antidepressants including MAOIs, SSRIs and tricyclics may antagonise the antiepileptic activity of phenobarbital by lowering the convulsive threshold.

Phenobarbital possibly reduces plasma levels of abacavir, amprenavir, darunavir, lopinavir, indinavir, nelfinavir, saquinavir.

Phenobarbital possibly reduces plasma concentration of aprepitant.

Phenobarbital possibly reduces concentration of aripiprazole.

Phenobarbital increases the rate of metabolism reducing serum concentrations of carbamazepine, lamotrigine, tiagabine, zonisamide, primidone and possibly ethosuxamide.

Phenobarbital increases the rate of metabolism reducing serum concentrations of chloramphenicol, doxycycline, metronidazole and rifampicin.

Concurrent use of chlorpromazine and thioridazine with phenobarbital can reduce the serum levels of either drug.

Phenobarbital increases the rate of metabolism reducing serum concentrations of ciclosporin or tacrolimus.

Phenobarbital increases the rate of metabolism reducing serum concentrations of clonazepam.

Blood levels of digitoxin can be halved by concurrent use.

Disopyramide and quinidine loss of arrhythmia control is possible. Plasma levels of antiarrhymics should be monitored, if phenobarbital is added or withdrawn. Changes in dosage may be necessary.

Concomitant use with eplerenone should be avoided.

Phenobarbital possibly reduces the plasma levels of etoposide or irinotecan.

Phenobarbital causes reduced levels of felodipine, isradipine, diltiazem, verapamil, nimodipine and nifedipine and an increase in dosage may be required.

The antifungal effects of griseofulvin can be reduced or even abolished by concurrent use.

Haloperidol serum levels are approximately halved by concurrent used with phenobarbital.

Phenobarbital possibly reduces plasma concentrations of itraconazole or posaconazole.

The effect of phenobarbital is possibly reduced.

Methadone levels can be reduced by concurrent use of phenobarbital and withdrawal symptoms have been reported in patients maintained on methadone when phenobarbital has been added. Increases in the methadone dosage may be necessary.

Plasma concentration of phenobarbital is possibly increased.

Phenobarbital increases the rate of metabolism reducing serum concentrations of metoprolol, timolol and possibly propranolol.

Phenobarbital increases the rate of metabolism reducing serum concentrations of montelukast.

Phenobarbital plasma concentrations increased by oxcarbazepine, phenytoin and sodium valproate.

Phenobarbital increases the rate of metabolism reducing serum concentrations of paroxetine, mianserin.

Avoid concomitant use of telithromycin during and for 2 weeks after phenobarbital.

Phenobarbital increases the rate of metabolism reducing serum concentrations of theophylline. May require an increase in theophylline dose.

Phenobarbital increases the rate of metabolism reducing serum concentrations of tibolone.

Phenobarbital increases the rate of metabolism reducing serum concentrations of tropisetron.

Vigabatrin possibly decreases phenobarbital plasma concentrations.

If folic acid supplements are given to treat folate deficiency, which can be caused by the use of phenobarbital, the serum phenobarbital levels may fall, leading to decreased seizure control in some patients.

Avoid concomitant use of voriconazole.

Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of phenobarbital. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment.

If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, phenobarbital treatment should be discontinued. The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis.

If the patient has developed SJS or TEN with the use of phenobarbital, it must not be re-started in this patient at any time.

Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomized placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for phenobarbital.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behavior emerge.

Phenobarbital increases the rate of metabolism reducing serum concentrations of gestrinone and possibly toremifene.

Phenobarbital therapy in epileptic pregnant women presents a risk to the fetus in terms of major and minor congenital defects such as congenital craniofacial, digital abnormalities and, less commonly, cleft lip and palate. The risk of teratogenic effects developing appears to be greater if more than one antiepileptic drug is administered. The risk to the mother, however is greater if phenobarbital is withheld and seizure control is lost. The risk: benefit balance, in this case, favours continued use of the drug during pregnancy at the lowest possible level to control seizures.

Patients taking Phenobarbital should be adequately supplemented with folic acid before conception and during pregnancy. Folic acid supplementation during pregnancy can help to reduce the risk of neural defects to the infant.

Phenobarbital readily crosses the placenta following oral administration and is distributed throughout fetal tissue, the highest concentrations being found in the placenta, fetal liver and brain. Adverse effects on neurobehavioral development have also been reported.

Haemorrhage at birth and addiction are also a risk. Prophylactic treatment with vitamin K₁ for the mother before delivery (as well as the neonate) is recommended, the neonate should be monitored for signs of bleeding.

Phenobarbital is excreted into breast milk and there is a small risk of neonatal sedation. Breast feeding is therefore not advisable.

Phenobarbital may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Patients should be advised to make sure they are not affected before undertaking any potentially hazardous tasks.