Phenytoin Capsules

Phenytoin sodium is an antiepileptic drug. Phenytoin sodium is related to the barbiturates in chemical structure, but has a five-membered ring. The chemical name is 5,5- Diphenylhydantoin sodium salt, having a molecular weight of 274.25 and having the following structural formula and molecular formula:

Each extended phenytoin sodium capsule, USP, for oral administration contains 200 mg or 300 mg of phenytoin sodium, USP. Each capsule also contains the following inactive ingredients: magnesium stearate, lactitol monohydrate, sodium lauryl sulfate, and talc. In addition, each of the empty gelatin capsules contains the following: gelatin, FD&C Blue # 1, FD&C Red # 40, D&C Red # 28 (200 mg) and FD&C Red # 3 (200 mg). The imprinting ink contains shellac, dehydrated alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide and potassium hydroxide. Product in vivoperformance is characterized by a slow and extended rate of absorption with peak blood concentrations expected in 4 to 12 hours as contrasted to prompt phenytoin sodium capsules, USP with a rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.

Extended phenytoin sodium capsules, USP 200 mg and 300 mg meet USP Dissolution Test 3.

Central Nervous System: The most common manifestations encountered with phenytoin therapy are referable to this system and are usually dose-related. These include nystagmus, ataxia, slurred speech, decreased coordination, and mental confusion. Dizziness, insomnia, transient nervousness, motor twitchings, and headaches have also been observed. There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs.

A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.

Gastrointestinal System: Nausea, vomiting, constipation, toxic hepatitis and liver damage.

Integumentary System: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, lupus erythematosus, Stevens-Johnson Syndrome, and toxic epidermal necrolysis (see PRECAUTIONS).

Hemopoietic System: Hemopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression. While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy. Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s Disease have been reported (see WARNINGS).

Connective Tissue System: Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hypertrichosis, and Peyronie’s Disease.

Immunologic: Hypersensitivity syndrome (which may include, but is not limited to, symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy or rash), systemic lupus erythematosus, periarteritis nodosa and immunoglobulin abnormalities.

Serum concentrations should be monitored in changing from extended phenytoin sodium capsules, USP to prompt phenytoin sodium capsules, USP, and from the sodium salt to the free acid form.

Extended phenytoin sodium capsules, USP 200 mg and 300 mg are formulated with the sodium salt of phenytoin. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.

General:

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustmentsthe clinically effective serum level is usually 10 to 20 mcg/mL. With recommended dosage, a period of 7 to 10 days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than 7 to 10 days.

Adult Dosage:

Divided Daily Dosage:

Patients who have received no previous treatment may be started on one 100 mg extended phenytoin sodium capsule three times daily and the dosage then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be one 100 mg capsule three to four times a day. An increase up to one 200 mg extended phenytoin sodium capsules, USP three times a day may be made, if necessary.

Once-A-Day Dosage:

In adults, if seizure control is established with divided doses of three 100 mg extended phenytoin sodium capsules daily, once-a-day dosage with 300 mg extended phenytoin sodium capsules may be considered. Studies comparing divided doses of 300 mg with a single daily dose of this quantity indicated absorption, peak plasma levels, biologic half-life, difference between peak and minimum values, and urinary recovery were equivalent. Once-a-day dosage offers a convenience to the individual patient or to nursing personnel for institutionalized patients and is intended to be used only for patients requiring this amount of drug daily. A major problem in motivating noncompliant patients may also be lessened when the patient can take this drug once a day. However, patients should be cautioned not to miss a dose, inadvertently.

Only extended phenytoin sodium capsules are recommended for once-a-day dosing. Inherent differences in dissolution characteristics and resultant absorption rates of phenytoin due to different manufacturing procedures and/or dosage forms preclude such recommendation for other phenytoin products. When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out.

Loading Dose:

Some authorities have advocated use of an oral loading dose of phenytoin in adults who require rapid steady-state serum levels and where intravenous administration is not desirable. This dosing regimen should be reserved for patients in a clinic or hospital setting where phenytoin serum levels can be closely monitored. Patients with a history of renal or liver disease should not receive the oral loading regimen.

Initially, one gram of Phenytoin Capsules is divided into three doses (400 mg, 300 mg, 300 mg) and administered at 2 hour intervals. Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations.

Pediatric Dosage:

Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years old and adolescents may require the minimum adult dose (300 mg/day).

Extended Phenytoin Sodium Capsules, USP are available containing 200 mg or 300 mg of phenytoin sodium, USP.

The 200 mg capsule has a blue transparent cap and a light blue transparent body. The hard-shell gelatin capsule is filled with white to off-white powder. The capsule is printed axially with 299 in black ink on both the cap and the body.

They are available as follows:

Bottle of 30's with Child Resistant Cap...................NDC 62756-299-83

Bottle of 100's with Child Resistant Cap.................NDC 62756-299-88

Bottle of 100's with Non Child Resistant Cap.........NDC 62756-299-08

Bottle of 500's with Non Child Resistant Cap.........NDC 62756-299-13

The 300 mg capsule has a light blue transparent cap and a light blue transparent body. The hard-shell gelatin capsule is filled with white to off-white powder. The capsule is printed axially with 432 in black ink on both the cap and the body.

They are available as follows:

Bottle of 30's with Child Resistant Cap...................NDC 62756-432-83

Bottle of 100's with Child Resistant Cap.................NDC 62756-432-88

Bottle of 100's with Non Child Resistant Cap.........NDC 62756-432-08

Bottle of 500's with Non Child Resistant Cap.........NDC 62756-432-13

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP for Controlled Room Temperature.] Protect from light and moisture. 

Dispense in a tight, light-resistant container as defined in the USP using a child resistant closure.

Distributed by:
Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512

Manufactured by:
Sun Pharmaceutical Industries Ltd.
Halol-Baroda Highway,
Halol-389 350, Gujarat, India.

ISS. 01/2015
PJPI0071C

Principal Display Panel - 200 mg

NDC 62756-299-83
Extended Phenytoin Sodium Capsules, USP
200 mg
Rx only
30 Capsules
SUN PHARMA

Principal Display Panel - 300 mg

NDC 62756-432-83
Extended Phenytoin Sodium Capsules, USP
300 mg
Rx only
30 Capsules
SUN PHARMA