Phenobarbital is a potent inducer of the hepatic enzyme system containing cytochrome P450 (mainly isoenzyme CYP3A4). Induction with phenobarbital occurs when it is used in doses as low as 60 mg per day. This property is the basis of pharmacokinetic interactions with other drugs, i.e. phenobarbital boosts both its own metabolism and the metabolism of many other drugs that undergo biotransformation in the liver. The latter have different effects on the action of barbiturates.
- Alcohol - simultaneous reception with alcohol can lead to potentiation of the oppressive effect on the central nervous system. The same effects are observed with simultaneous admission with other CNS depressants.
- Antidepressants - including MAO inhibitors, SSRIs and TCAs can reduce the antiepileptic activity of phenobarbital by reducing the convulsive threshold.
- Antiepileptic agents - plasma concentrations of phenobarbital increase with simultaneous reception with oxcarbazepine, phenytoin and sodium valproate. Vigabatrin - there is evidence of a decrease in the plasma concentration of phenobarbital.
- Neuroleptics - simultaneous use of aminazine or thioridazine with phenobarbital may lead to a mutual decrease in plasma concentration.
- Folic acid - administration of folic acid preparations for the treatment of folic acid deficiency, which can be observed with the use of phenobarbital, causes a decrease in the plasma level of phenobarbital, which leads to inadequate control of seizures in some patients.
- Memantine - the effectiveness of phenobarbital may decrease.
- Methylphenidate - can increase the plasma concentration of phenobarbital.
- Drugs based on St. John's wort perfumed - The effectiveness of phenobarbital can be reduced with simultaneous application.
Effects of phenobarbital on other drugs
Phenobarbital increases the metabolic rate of the following drugs, which leads to a decrease in plasma concentrations:
- antiarrhythmics - disopyramide and quinidine - It is possible to reduce the concentrations of anti-arrhythmic effect. When appointing or abolishing phenobarbital, control of plasma concentrations of antiarrhythmics is necessary. You may need to change their dosing regimen;
- antibacterial drugs - levomycetin, doxycycline, metronidazole and rifampicin. It is necessary to avoid simultaneous use of telithromycin against the background and within 2 weeks after taking phenobarbital;
- anticoagulants;
- antidepressants - paroxetine, mianserin and tricyclic antidepressants;
- antiepileptic means - carbamazepine, lamotrigine, tiagabine, zonisamide, primidon and, possibly, ethosuccide;
- antifungal drugs - the antifungal effect of griseofulvin can be reduced or absent whensimultaneous reception with phenobarbital. Phenobarbital probably reduces plasma concentrations of itraconazole and posaconazole. It is not recommended to share with voriconazole;
- antipsychotics - phenobarbital, possibly reduces the plasma concentration of aripiprazole;
- antiviral drugs - phenobarbital possibly reduces plasma concentrations of abacavir, amprenavir, darunavir, lopinavir, indinavir, nelfinavir, saquinavir;
- anxiolytics and hypnotics - clonazepam;
- aprepitant - phenobarbital it is possible to reduce the concentration in the plasma of aprepitant;
- beta-blockers - metoprolol, timolol and, perhaps, propranolol;
- calcium channel blockers - phenobarbital leads to a decrease in the level of felodipine, isradipine, diltiazem, verapamil, nimodipine and nifedipine, which may require increasing their doses;
- cardiac glycosides - when used simultaneously with phenobarbital, the concentration in the blood of digitoxin can be halved;
- cyclosporine and tacrolimus; corticosteroids;
- cytostatics - phenobarbital possibly reduces the plasma concentrations of etoposide and irinotecan;
- diuretics - do not recommend simultaneous use of phenobarbital with eplerenone;
- haloperidol - plasma concentrations are reduced by about half when used simultaneously with phenobarbital;
- antagonists of hormones - gestrinone and, perhaps, toremifene;
- methadone - when used concomitantly with phenobarbital plasma concentrations and withdrawal symptoms may appear, which may require an increase in the dose of methadone;
- montelukast;
- estrogens - decreased contraceptive effect;
- progestogens - decreased contraceptive effect;
- theophylline - may require an increase in the dose of theophylline;
- thyroid hormones - may require an increase in thyroid hormone doses for hypothyroidism;
- tibolone;
- troposetron;
- vitamins - barbiturates possibly increase the need for vitamin D.
Enhances the effects of sodium oxybutyrate. Joint use is not recommended.
Phenobarbital can change diagnostic tests with cyanocobalamin, with metiapone, phentolamine (false positive test).