Label Changes for:
Dilantin-125 (phenytoin) Oral Suspension
Changes have been made to the PRECAUTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Drugs affected by phenytoin
- Phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite. Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir.
- Resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents pancuronium, vecuronium, rocuronium, and cisatracurium has occurred in patients chronically administered phenytoin. Whether or not phenytoin has the same effect on other nondepolarizing agents is unknown. Patients should be monitored closely for more rapid recovery from neuromuscular blockade than expected, and infusion rate requirements may be higher
- Coadministration of Dilantin is contraindicated with delavirdine due to potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.
Drug Interactions (revised)
- Phenytoin is extensively bound to serum plasma proteins and is prone to competitive displacement. Phenytoin is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19, and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes. Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected.
The most commonly occurring drug interactions are listed below:
Note: The list is not intended to be inclusive or comprehensive. Individual drug package inserts should be consulted.
Drugs that affect phenytoin concentrations:
- Drugs, which may increase phenytoin serum levels, include: acute alcohol intake, amiodarone,anti-epileptic agents (felbamate, topiramate, oxcarbazepine), azoles (fluconazole, ketoconazole,itraconazole, voriconazole), chloramphenicol, chlordiazepoxide, cimetidine, diazepam, disulfiram,estrogens, ethosuximide, fluorouracil, fluoxetine, fluvoxamine, H2-antagonists, halothane,isoniazid, methylphenidate, omeprazole, phenothiazines, salicylates, sertraline, succinimides,sulfonamides, ticlopidine, tolbutamide, trazodone, and warfarin.
- Drugs, which may decrease phenytoin levels, include: carbamazepine, chronic alcohol abuse,nelfinavir, reserpine, ritonavir, and sucralfate.
- Ingestion times of phenytoin and antacid preparations containing calcium should be staggered inpatients with low serum phenytoin levels to prevent absorption problems.
- Drugs which may either increase or decrease phenytoin serum levels include: phenobarbital,sodium valproate, and valproic acid. Similarly, the effect of phenytoin on phenobarbital, valproicacid, and sodium valproate serum levels is unpredictable.
- The addition or withdrawal of these agents in patients on phenytoin therapy may require anadjustment of the phenytoin dose to achieve optimal clinical outcome.
Drugs affected by phenytoin:
- Drugs that should not be coadministered with phenytoin: Delavirdine
- Drugs whose efficacy is impaired by phenytoin include: azoles (fluconazole, ketoconazole, itraconazole, voriconazole), corticosteroids, doxycycline, estrogens, furosemide, irinotecan, oral contraceptives, paclitaxel, paroxetine, quinidine, rifampin, sertraline, teniposide, theophylline, vitamin D, and warfarin.
- Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin.
- Phenytoin decreases plasma concentrations of certain HIV antivirals (amprenavir, efavirenz, Kaletra (lopinavir/ritonavir), indinavir, nelfinavir, ritonavir, saquinavir), and anti-epileptic agents (felbamate, topiramate, oxcarbazepine, quetiapine).
- The addition or withdrawal of phenytoin during concomitant therapy with these agents may require adjustment of the dose of these agents to achieve optimal clinical outcome.
Body As a Whole: Allergic reactions in the form of rash and rarely more serious forms (see Skin and Appendages paragraph below) and DRESS (see WARNINGS) have been observed. Anaphylaxis has also been reported.
There have also been reports of coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.
- Digestive System: …enlargement of the lips, gingival hyperplasia,
- Skin and Appendages: …There have also been reports of hypertrichosis.
- Special Senses: Altered taste sensation including metallic taste.
- Urogenital: Peyronie’s disease