This panel provides information on interacting drugs and their ADRs along with references
| Interacting drug |
Toxicity |
Interaction Type |
Mechanism |
Reference |
|---|
| Disopyramide ((3737-09-5)) | Loss Of Arrhythmic Control | Antagonistic | Phenytoin, which is a known enzyme-inducer, increases the metabolism
of the disopyramide by the liver. Although, the major metabolite
(N-dealkyldisopyramide) also possesses antiarrhythmic activity the net
effect is a reduction in arrhythmic control | Effect of phenytoin on serum disopyramide concentrations
|
| Lidocaine (137-58-6) | Sinoatrial Arrest | Additive | Phenytoin and lidocaine appear to have additive cardiac depressant actions. The reduced lidocaine serum levels are possibly due to liver enzyme induction when lidocaine is given orally the marked reduction in levels results from the stimulation of hepatic first-pass metabolism by phenytoin. In addition, patients taking antiepileptics including phenytoin had higher plasma concentrations of alpha-1-acid glycoprotein, which may result in a lower free fraction of lidocaine in the plasma | Plasma levels of lidocaine during combined treatment with phenytoin and procainamide
|
| Streptozocin (18883-66-4) | Abolish The Effects Of Streptozocin | Antagonistic | Unknown | Influence of diphenylhydantoin on the effect of streptozotocin
|
| Teniposide (29767-20-2) | Haematological Relapse And Cns Relapse | Antagonistic | antiepileptics are potent liver enzyme inducers, which may increase the metabolism of teniposide by the liver | Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia
|
| Praziquantel (55268-74-1) | Neurocysticercosis Treatment Failures | Antagonistic | Not established | Phenytoin and carbamazepine decreased oral bioavailability of praziquantel
|
| Quinidine (56-54-2) | Loss Of Arrhythmia Control | Antagonistic | The evidence suggests that phenytoin, primidone or phenobarbital (all known enzyme-inducers) increase the hepatic metabolism of quinidine and thereby reduce its levels | Interaction of quinidine with anticonvulsant drugs
|
| Albendazole (54965-21-8) | Reduce Efficacy For Systemic Infections | Antagonistic | Phenytoin appear to induce the oxidative
metabolism of albendazole by the cytochrome P450 isoenzyme
CYP3A to roughly the same extent, resulting in significantly reduced levels
of albendazole sulfoxide. | Pharmacokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neurocysticercosis
|
| Allopurinol (315-30-0) | Nystagmus | Synergistic | not known | Drug interaction between phenytoin and allopurinol
|
| Amiodarone (1951-25-3) | Ataxia | Synergistic | Uncertain. It seems possible that amiodarone inhibits the liver enzymes concerned with the metabolism of phenytoin, resulting in a rise in its serum levels | Steady-state interaction between amiodarone and phenytoin in normal subjects
|
| Apazone (13539-59-8) | Phenytoin Toxicity | Synergistic | azapropazone inhibits the liver enzymes concerned with the metabolism of phenytoin, resulting in its accumulation | Interaction of azapropazone with phenytoin
|
| Carbamazepine (298-46-4) | Neurotoxicity | Synergistic | Not understood,carbamazepine can inhibit the cytochrome P450 isoenzyme CYP2C19, which is one of the enzymes involved in phenytoin metabolism.19 Carbamazepine might therefore cause increases in phenytoin levels by this mechanism. | Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19
|
| Chloramphenicol (56-75-7) | Phenytoin Toxicity | Synergistic | Chloramphenicol is a enzyme inducer affects the liver enzymes (possibly cytochrome P450 isoenzyme CYP2C1915) concerned with the metabolism of phenytoin thereby reducing its rate of clearance from the body | Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes
|
| Chlorphenamine (132-22-9) | Involuntary Jaw Movements | Synergistic | The reason for these reactions is not clear but it has been suggested that chlorphenamine may have inhibited the metabolism of phenytoin by the liver. | Involuntary movements caused by phenytoin intoxication in epileptic patients
|
| Cimetidine (51481-61-9) | Bone Marrow Depression | Synergistic | Cimetidine inhibits the activity of the liver enzymes concerned with the metabolism of phenytoin, thus allowing it to accumulate in the body | Cimetidine interaction with phenytoin
|
| Ciprofloxacin (85721-33-1) | Decreased Phenytoin Levels | Antagonistic | The mechanism for the effect of ciprofloxacin
on phenytoin levels is unknown, and is unlikely to be due to effects
on hepatic metabolism or oral absorption | ciprofloxacin-phenytoin interaction
|
| Cisplatin (15663-27-1) | Seizures | Antagonistic | Not fully understood, but a suggested reason for the fall in serum antiepileptic levels is that these antineoplastics damage the intestinal wall, which reduces the absorption of the antiepileptic | Decreased phenytoin levels in patients receiving chemotherapy
|
| Co-trimoxazole (8064-90-2) | Nystagmus | Synergistic | inhibiting the metabolism of the phenytoin by the liver (possibly by the cytochrome P450 isoenzyme CYP2C9) | Phenytoin intoxication and cotrimoxazole
|
| Diazoxide (364-98-7) | Seizure Control Lost | Antagonistic | diazoxide increases the metabolism and the clearance of phenytoin from the body. The half-life of diazoxide is possibly reduced by phenytoin | Drug interaction: diazoxide and diphenylhydantoin
|
| Dicumarol (66-76-2) | Phenytoin Toxicity | Synergistic | Dicoumarol appear to inhibit the metabolism of phenytoin by the liver, so that its loss from the body is reduced. Phenytoin is an inducer of the cytochrome P450 isoenzyme CYP2C9, which is involved in metabolism of the coumarin anticoagulants | Dicoumarol-induced diphenylhydantoin intoxication
|
| Disulfiram (97-77-8) | Rise In Phenytoin Serum Levels | Synergistic | Disulfiram inhibits the liver enzymes concerned with the metabolism of phenytoin (possibly the cytochrome P450 isoenzyme CYP2C9) | Mathematical analysis of a phenytoin-disulfiram interaction
|
| Fluconazole (86386-73-4) | Phenytoin Toxicity | Synergistic | Fluconazole inhibits the cytochrome P450 isoenzymes responsible for phenytoin metabolism (probably CYP2C9) | Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man
|
| Fluoxetine (54910-89-3) | Abnormal Thinking | Synergistic | Fluoxetine inhibited the metabolism of phenytoin by the cytochrome P450 isoenzyme CYP2C9 in human liver tissue. | Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro: studies of phenytoin p-hydroxylation
|
| Folic Acid (59-30-3) | Seizure Control Is Partially Or Totally Lost | Antagonistic | Patients taking antiepileptics may have subnormal serum folic acid levels. Frequencies of 27 to 76% have been reported for phenobarbital, primidone, and phenytoin alone or in various ombinations.8 One possible explanation
is that this is due to the enzyme-inducing characteristics of these
antiepileptics, which makes excessive demands on folate for the synthesis
of the enzymes concerned with drug metabolism | Folic acid deficiency in patients receiving anticonvulsant drugs
|
| Imipramine (50-49-7) | Drowsiness | Synergistic | imipramine inhibits the metabolism of the phenytoin by the liver, which results in its accumulation in the body. In vitro study has shown that the tricyclics can inhibit the cytochrome P450
isoenzyme CYP2C19 | Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin
|
| Isoniazid (54-85-3) | Phenytoin Toxicity | Synergistic | Isoniazid inhibits the liver microsomal enzymes that metabolise phenytoin, and as a result the phenytoin accumulates and its serum levels rise | Inhibition of Cytochrome P450 (CYP450) Isoforms by Isoniazid: Potent Inhibition of CYP2C19 and CYP3A
|
| Nitrofurantoin (67-20-9) | Seizure Control Lost | Antagonistic | Not understood | Interaction of nitrofurantoin with diphenylhydantoin
|
| Sultiame (61-56-3) | Phenytoin Toxicity | Synergistic | sultiame interferes with the metabolism of the
phenytoin by the liver, leading to its accumulation in the body. | Drug--interaction between sulthiame (Ospolot (R)) and phenytoin in the treatment of epilepsy
|
| Tamoxifen (10540-29-1) | Phenytoin Toxicity | Synergistic | tamoxifen and phenytoin both compete for the same metabolising
enzymes. | High-dose tamoxifen in treatment of brain tumors: interaction with antiepileptic drugs
|
| Thioridazine (50-52-2) | Phenytoin Toxicity | Synergistic | Uncertain. Phenothiazines such as thioridazine are inhibitors of the cytochrome P450 isoenzyme CYP2D6 | Inhibition of phenytoin metabolism by other drugs used in epilepsy
|
| Ticlopidine (55142-85-3) | Somnolence | Synergistic | The metabolism of phenytoin to 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) by the cytochrome P450 isoenzyme CYP2C19, and to a lesser extent by CYP2C9, in the liver is inhibited by ticlopidine. Further metabolism of HPPH to dihydroxylated products is mediated mainly by CYP2C19 and this may also be inhibited by ticlopidine | Ticlopidine impairs phenytoin clearance: a case report
|
| Tolbutamide (64-77-7) | Increase In Blood Glucose | Synergistic | phenytoin-induced hyperglycaemia occurs because the release of insulin from the pancreas is impaired,and antidiabetics
competitively inhibit phenytoin hydroxylation by the cytochrome P450 isoenzyme CYP2C9. | The in vitro inhibition of insulin secretion by diphenylhydantoin
|
| Valproic Acid (99-66-1) | Hepatotoxicity | Antagonistic | The initial fall in total serum phenytoin levels appears to result from the displacement of phenytoin from its protein binding sites by valproate, the extent being subject to the diurnal variation in valproate levels. This allows more of the unbound drug to be exposed to metabolism by the liver and the total phenytoin levels fall | Valproic acid in epilepsy: clinical and pharmacological effects
|
| Vigabatrin (60643-86-9) | Increase In Seizure Frequency | Antagonistic | Not understood | A multicentre study of vigabatrin for drug-resistant epilepsy
|
| Viloxazine (46817-91-8) | Nystagmus | Antagonistic | Uncertain | Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction
|
| Progabide (62666-20-0) | Serum Phenytoin Level Increased | Synergistic | Uncertain | Effect of progabide on serum phenytoin and carbamazepine concentrations
|
| Procarbazine (671-16-9) | Hypersensitivity | Synergistic | enzyme-inducing antiepileptics may increase the metabolism of procarbazine to metabolites | Anticonvulsant usage is associated with an increased risk of procarbazine hypersensitivity reactions in patients with brain tumors
|
| Zonisamide (68291-97-4) | Decreased Zonisamide Serum Level | Antagonistic | Uncertain | The necessity of adjusting the dosage of zonisamide when coadministered with other anti-epileptic drugs
|