EPILAN
Manufacturer DetailsAFD
Anglo-French Drugs & Industries Ltd # 41 3rd Cross V Block S.S.T Rajajinagar Bangalore 56010
Compositions:
Phenytoin sod 100mg+ Phenobarbitone 30mg tablets,
Phenytoin sod 100mg+ Phenobarbitone 30mg tablets,
| Strength | Rate | Packing Style |
|---|---|---|
| 100mg+30mg | 367.42 | 10s tablets |
List of Related Indications:
- Grand mal
- Migraine
- Psychomotor seizures
- Trigeminal neuralgia
- Vascular headache
List Of Drugs:
- Phenytoin Sodium - @- ( *** ) - Anticonvulsant- (June 2007)
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Other Information
Patient Information
Pharmacology/ Pharmacokinetics
Interaction with Food
Pregnancy and lactation
Drug Interaction:
Anticonvulsants -
BARBITURATES - OXAZOLIDINEDIONES- MISCELLANEOUS-
Phenobarbitone Paramethadione Lamotrigine
Trimethadione Primidone
HYDANTOINS- Valproic acid
Phenytoin BENZODIAPINES- Cabamazepine
Mephenytoin Clonazepam Phenacemide
Ethotoin Clorazepate Felbamate
Diazepam Gabapentin
SUCCINIMIDES-
Ethosuximide
Methsuximide
Phensuximide
Refer Phenytoin Sodium -
Hydantoin group includes -
Ethotoin, fosphenytoin, phenytoin-
Refer Phenytoin Sodium
Interacting drugs - summary
Hydantoin +
Warfarin
anticoagulant effect of Warfarin increased
Quinidine
therapeutic effect of Quinidine decreased
Disopyramide
Disopyram serum levels,half-life and bioavailabilty may be
decreased
Mexiletine
Mexilitine absorbtion increased
Estrogens / Estrogen + Hydantoins
breakthrough bleeding, spotting and pregnancy resulted
when these agents were used concurrently.
Contraceptives Oral
May increase the hepatic metabolism of the OCs. resulting in
decreased effectiveness of OCs; menstrual irregularties
(spotting, breakthrough bleeding) and pregnancy may occur.
An alternate or additional form of birth control may be
advisable
Corticosteroids
corticosteroid clearance may be increased, resulting in
reduced therapeutic effects
Sulfonylureas
the hypoglycemic effect of the sulfonylureas may be
decreased due to various mechanisms
Verapramil
serum verapramil levesl may be decreased
Lamotrigine
lamotrigine concentration is decreased
Nondepolarizing neuromuscular blockers (NNBs)
NNBs may have a shorter than expected duration or be less effective
Phenytoin + Atracurium
Phenytoin and theophylline may cause resistence to, or reversal of,
the Theophylline neuromuscular blocking action of atracurium
Levodopa
Levodopas effectiveness may be reduced
Chloramphenicol + Hydantoin /or Hydantoin + Chloramphenicol
serum hydantoin levels may be increased , possibly resulting in toxicity.
In addition, chloramphenicol levels may be increased or decreased
Tetracycline
may increase the rate of metabolism and therefore decrease the
half-life and serum levels of doxycycline. Antimicrobial effectiveness
decreased
Phenytoin + Itraconazole /or Itraconazole + Phenytoin
reduced plasma itraconazole levels may occur. Also phenytoin
metabolism may be altered
Zalcitabine
these drugs are associated with peripheral neuropathy
Avoid concomittant use when possible
+ Hydantoin
Phenytoin
concomittant administratiion mat result in a loss of seizure control, possibly
due to increased hepatic metabolism of phenytoin
NSAIDs
serum phenytoin levels may be increased, resulting in an increase in
pharmacologic and toxic effects of phenytoin
Phenytoin + Paroxetine / or Paroxetine/ Fluoxetine + Phenytoin
phenytoin reduced the AUC and half-life of paroxetine.
Also paroxetine reduced the AUC of phenytoin and fluoxetine may
increase hydantoin levels.
Barbiturate
the effect of barbiturates on metabolism is unpredictable, monitor hydantoin
and barbiturate blood levels frequently, if these drugs are given concurrently
Quinidine
a decrease in the therapeutic effect of quinidine may occur
Phenytoin
increased action of phenytoin even at therapeutic levels or increased
Phenytoin + Valproic acid
metabolism of valproic acid with decreased pharmacologic effects may occur.
Hydantoin / Carbamazepine + Hydantoin
Both increased/decreased hydantoin plasma level,as well as decreased
carbamazepine level have ocured during co-administration
Sucralfate
phenytoin absorption may be decreased
Omeprazole/ Ciprofloxacin + Hydantoin
Omeprazole reduced plasma clearance of Phenytoin.
phenytoin serum levels may be reduced , producing a decrease in
therapeutic effects
Metronidazole
total clearance of Hydantoin decreased and its elimination half-life
prolonged
Pyridoxine + Phenytoin
phenytoin serum levels may be decreased
Charcoal
charcoal can reduce absorption of these drugs and actually remove
them from systemic circulation which may reduce effectiveness of a
given agent. Charcoal is also used as an antidote for overdoses.
Fluconazole
coadministration resulted in an increase of phenytoin AUC values
Sulfonamides + Hydantoins
serum hydantoin levels may be increased
Zidovudine + Phenytoin or Phenytoin + Zidovudine
phenytoin levels have been reported to increase , decrease or not
change with concurrent use. In addition, zidovudine, clearance was
decreased by phenytoin
TMP+ SMZ
phenytoins hepatic clearance may be decreased and half-life
prolonged
Typhoid vaccine
concomittant phenytoin therapy may decrease antibody response
to SC typhoid vaccination.
Influenza virus vaccine
influenza vaccination reportedly inhibits the clearance
of these agent,
Vinblastine
combination therapy may reduce phenytoin plasma levels. Adjust
dosage based on serial blood level monitoring
Tacrolimus
these agents may decrease tacrolimus blood levels
Mycophenolate
MPA decreased the binding of phenytoin
Succinimides
serum hydantoin levels may be increased
Indication:
LIST OF DRUGS DURING 2007
Sr.No- 86
Name of the Drug- Phenytoin sodium ER capsules
(300mg) (New dosage form) Pharmacological Classification- For Control of generalized toniclonic and
treatment & prevention of seizures
occuring during or following neurosurgery
Date of Approval- 14-06-07
Approved by U.S.FDA on 30-12-2007 (Ref- FDA approved List- 2007)
LIST OF DRUGS DURING 2007
Sr.No- 95
Name of the Drug- Phenytoin sodium ER (300mg) Pharmacological Classification- For Control of generalized toniclonic
(grand mal) and prevention and treatment
of seizures occuring during or following
neurosurgery
Date of Approval- 14-06-07
Approved by U.S.FDA on 30-12-2007 (Ref- FDA approved List- 2007)
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Phenytoin Sodium ER capsules 14-06-2007
300mg - New Dosage Form
For Control of generalized toniclonic and treatment & prevention of
seizures occuring during or following neurosurgery
Anticonvulsant
Adverse Reaction:
CNS-(most common) -Nystagmus, ataxia, dysarthia, slurred speech, mental confusion, dizziness, insomnia, transcient nervousness, fatigue, irritability, drowsiness, tremor headache. Side effects may disappear after reducing dosage.
Cardiovascular-
Phenytoin IV- cardiovascular collapse,CNS depression, hypotension) whenrapid IV admin of drug IV, Monitor rate of administration.Cardiotoxic reactions and fatalities have occurred occurred in elderly or gravely ill patients.
GI-
Nausea, vomiting, diarrhea, constipation. Administration of the drug with or immediately after meals may help to prevent GI discomfort.
Gingival hyperplasia-
occurs frequently with phenytoin, incidence reduced by good oral hygiene, gum message, and appropriate dental care.
Hepatic-
Toxic hepatitis and liver damage may occur very rarely and can be fatal.
Dermatologic-
Manifestations sometimes accompanied by fever.
Rashes are frequent in children and young adults
Hematologic-
Complication, some fatal include thrombocytopenia, leukopenia, granulocytopenia,
agranulocytosis, and pancytopenia. Megaloblastic anemia uually respond to
folic acid therapy.
Body as a whole-
Hyperglycemia, weight gain, chest pain, edema, fever, photophobia,
Lab test abnornalities-
Phenytoin may decrease serum thyroxine and free thyroxine concentrations.
Contra-Indications:
A.V.block.Pregnancy,lactation,acute intermitant porphyria.
Special precautions:
Impaired liver function,Haemopoietic complications.Withdraw drug slowly.Elderly or seriously
ill patients. monitor ECG, children(need higher doses).
Hematologic effects- perform blood counts and urinalysis when therapy is begun and at monthly intervals for several months thereafter. Blood dyscrasias have ocurred. Avoid use in combination with other drugs known to adversely affect the mematopoietic system.
Dermatologic effects- If skin rask appears, discontinue use.. If rash is exfoliative , purpuric or bullous, do not resume use. If the rash is milder , resume therapy after it has completely disappeared
Hypersensitivity- Alternative therapy may be necessary in case of hypersenstivity or allergic reaction but should should not belong hydantoin chemical class.
Hyperglycemia- Hydantoins may also raise blood sugar levels in hyperglycemic persons.
Cardiovascular- death and cardiac arrest has occured after too rapid IV administartion.
Observe the patient closely when the drug is adminisitered by IV route.
Osteomalcia- has been associated with phenytoin therapy
Warnings-
Abrupt withdrawal in epileptic patienst may precipitate status epilepticus. Reduce dosage ,
discontiue or substitute other anticonvulsant mediaction gardually
Other seizures- hydantoins are not indicated in seizures due to hypoglycemia or other meatbolic causes. Perform appropiate diagnostic procedures
Phenytoin- use with caution in hypertension and myocardial insufficiency
Hepatic function impairment- Disconinue drug if hepatic dysfunction occurs.
Pregnancy- Carfully access need if nature,frequency and severity of the seizures do not pose a serious threat to the patient.
Lactation- In view of the potential for serious adverse reactions in nursing infants, decide whether to discontinue nursing or discontinue the drug.
Dosages/ Overdosage Etc:
Date of Approval 2007
Indications:
Anticonvulsant
Dosage:
Oral- adult- initial 100mg 3 times daily
Individualise dose.Satisfactory maintenance dose- 300 to 400mg/day
Drug/Lab test interaction:
Phenytoin may interfere with methylpyrone and 1mg dexamethasone tests.Discontinuing
hydantoin prior to methypone testing would be ideal, but not practical. Consider doubling the
oral metyraprone dose.
Overdosage-
Symptoms
The lethal dose in adults is estimated to be 2 to 5 g.
Initial symptoms are,nystagmus,ataxia,and dysarthia. The patient may then become comatose
and hypotensive, with pupils inresponsive.
Treatment
1. Treatment is no specific, there is no specific antidote.
2. Consider hemodialysis, since phenytoin is not completely bound to plasma proteins.
3. Total exchange transfusion has been utilized in the treatment of severe intoxification in children.
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Other Information:
Exfoliative dermatitis- ( 241)-
Erythroderma syndrome
Erythroderma syndrome- is an important dermatologic complication that may occur as the result of an extension of a drug reaction as a generalised spreading of preexisting dermatitis., such as psoroiasis or atopic dermatitis or in association with lymphoma and leukemia. This syndrome consists of a generalized erythematous scaling eruption invovling all of the skin surface and has important implications in general medicine because of the systemic effects occassioned by the massive and continuous exfoliation of the skin.
Drugs causing adverse reactions- ( 386 )
1. Penicilins
2. Sulfonamides
3. Barbiturates
4. Phenytoin
5. Phenylbutazone
6. Gold salts
7. Quinidine
Gingival Hyperplasia-
Drugs causing advese reactions - ( 385 )
1. Phenytoin
Patient Information:
Refer phenytoin sodium -
1.Take medication with food to reduce GI upset.
2.Phenytoin suspension must be throughly shaken immediately prior to use.
3.Do not discontinue medication abruptly or change dosage, except on advise of physician.
4.Maintain good oral hygeine(regular brushing and flossing) while taking phenytoin. Inform
dentist of medication usuage.
5.Patients should carry identification, indicating medication usuage and epilepsy.
6.Do not use capsules which are discoloured.
7.Diabetic patients, monitor urine sugar regularly and report abnormalities to the physician
8. Notify physician if any thing abnormal occurs.
9.Allergies- Tell your doctor if you are allergic to other substances such as foods, preservative or dyes.
10. Pregnancy- There have reports of increased birth defects when these nedicines are used during prergnancy.
Pregnancy may cause a change in the way the hydantoin anticonvulsants are absorbed in your body.
11. Breast feeding- Phenytoin pass into breast milk in small amounts. Be sure you have discussed the risks and benefits of the medicine with your doctor.
12. Children- Some side efects especially bleeding tender or enlarged gums facial features are most likely to occur in children and young adults. Some children may not do as well in school after using high doses of this medicine for a long time.
13. Elderly- Overdose is most likely to occur in elderly patients and in patients with liver disease.
14. Other medicines- When you are receiving hydantoin convulsants it is important that your doctor know what other medicines you are taking so that he can advice you accordingly.
15 Other medical problems- Tell your doctor of your other medical problems to enable him to advice properly.
16. Missed dose -
If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.
17. Storage -
Keep out of reach of children. Store away from heat or direct sunlight. Do not store
the capsule in bathroom, near the kitchen sink, or in other damp places.
18. Outdated medicines -
Do not keep outdated medicine or medicine no longer needed. Be sure that any
discarded medicine is out of reach of children.
Pharmacology/ Pharmacokinetics:
Ref- Drug Facts And Comparisons(2010)
Hydantoin group includes -
Ethotoin, fosphenytoin, phenytoin-
Refer Phenytoin Sodium
Pharmacology:
The primary site of action appears to be the motor cortex,where the spread of seizure activity is inhibited.Hyantoin tend to to stabilise the threshold against hyperexcitabilty caused bystimulation or environmental changes.
Pharmacokinetics:
Phenytoin is slowly absorbed from the small intestine.Oral phenytoin sodium extended
reaches peak plasma levels in 12 hours,phenytoin sodium prompt peak within 1.5 to 3 hours.
Metabolism:
Phenytoin is metabolised in liver into inactive hydroxylated metabolites and excreted in the
urine by tubular secretion.
Hydantoins- Summary of Pharmacokinetics-
Parameters
Tmax Protein Plasma Elimint Excretn Therapeu
(h) binding half-life half-life plasma
% conc.
mcg/mL
Drug
Ethiotion
2-4 hr 46 - 3-12 hrs - 15 to 50
single
dose
Fosphenytoin
IV- end of 95-99% app - Renal 10 to20
infusion 15 min (0-4%) mcg/mL
(phenytoin (phenytoin)
plasma
conc peak
in 30 min
IM- 30 min
post dose
(phenytoin
plasma
conc peak
in app 3 hrs
Phenytoin
Chewable tablets
1.5 to 3 hrs app 14 hrs - urine and feces 10 to 20
90% range (as inactive mcg/mL
range (7-29hrs) metabolite)
(69-96%)
ER Capsules
4 to 12 hrs app 22hrs - urine and feces 10 to 20
90% range (as inactive mcg/mL
range (7-42) metabolite)
(69-96%)
Oral Suspension
1.5 to 3hrs app 22hrs - urine and feces 10 to 20
90% range (as inactive mcg/mL
range (7-42) metabolite)
(69-96%)
Injection
24 hrs app 10-15hrs 24hr for urine and feces 10 to 20
90% (IV) conc (as inactive mcg/mL
range of metabolite)
(69-96%) 10mcg
/mL
Interaction with Food:
Food may delay absorption- consider giving phenytoin 2 hours before a meal.
Pregnancy and lactation:
Pregnancy:
Consider discontinuation of anticonvulsant prior to and during pregnancy when the nature, frequency and severity of the seizures do not pose a serious threat to the patient
Lactation:
Because of the potential serious adverse reaction to the nursing infant, observe caution and decide whether to discontinue the drug or discontinue the drug.
