PHENYTOIN SODIUM capsule, extended release

United States - English - NLM (National Library of Medicine)

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Active ingredient:
PHENYTOIN SODIUM (UNII: 4182431BJH) (PHENYTOIN - UNII:6158TKW0C5)
Available from:
REMEDYREPACK INC.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Extended phenytoin sodium capsules, USP are indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. Extended phenytoin sodium capsules are contraindicated in patients with: - A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see Warnings and Precautions (5.5)] . - A history of prior acute hepatotoxicity attributable to phenytoin [see Warnings and Precautions (5.7)]. - Coadministration with delavirdine because of the potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as extended phenytoin sodium capsules, during preg
Product summary:
Extended Phenytoin Sodium Capsules USP, 100 mg are hard gelatin capsules No. 3 with an opaque orange body and cap, imprinted "TARO PHN 100" in black ink. They are available in: Store at 20˚ to 25˚C (68˚ to 77˚F) [See USP Controlled Room Temperature]. Preserve in tight, light-resistant containers. Protect from moisture.
Authorization status:
Abbreviated New Drug Application
Authorization number:
70518-2293-0

REMEDYREPACK INC.

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This Medication Guide has been approved by the U.S. Food and Drug Administration.

MEDICATION GUIDE

Extended Phenytoin (fen ´ i toin) Sodium Capsules, USP

What is the most important information I should know about extended phenytoin sodium capsules?

Do not stop taking extended phenytoin sodium capsules without first talking to your healthcare

provider.

Stopping extended phenytoin sodium capsules suddenly can cause serious problems.

Stopping a seizure medicine suddenly can cause you to have seizures more often or seizures

that will not stop (status epilepticus).

Like other antiepileptic drugs, extended phenytoin sodium capsules may cause suicidal thoughts or

actions in a very small number of people, about 1 in 500. Call a healthcare provider right away if you

have any of these symptoms, especially if they are new, worse, or worry you:

Thoughts about suicide or dying

Attempts to commit suicide

New or worse depression

New or worse anxiety

Feeling agitated or restless

Panic attacks

Trouble sleeping (insomnia)

New or worse irritability

Acting aggressive, being angry, or violent

Acting on dangerous impulses

An extreme increase in activity and talking

(mania)

Other unusual changes in behavior or mood

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or

actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Extended phenytoin sodium capsules can cause a type of serious allergic reaction that may affect

different parts of the body such as your liver, kidneys, blood, heart, skin or other parts of your body.

These can be very serious and cause death. Call your healthcare provider right away if you have any

or all of these symptoms:

Fever

Rash

Swollen lymph glands

Swelling of your face, eye, lips, or tongue

Trouble swallowing or breathing

Sore throat

Sores in your mouth

Bruise easily

Purple or red spots on your skin

Increase infections

Not wanting to eat (anorexia)

Nausea

Vomiting

Yellowing of the skin and the white part of

your eyes (jaundice)

Call your healthcare provider even if the symptoms are mild or if you have been taking extended phenytoin

sodium capsules for an extended period of time. These symptoms can be a sign of a serious allergic reaction.

Phenytoin can cause problems with your heart, including a slow heartbeat. Let your healthcare

provider know right away if you have any of these symptoms:

dizziness

tiredness

feeling like your heart is beating slowly or skipping beats

chest pain

What are extended phenytoin sodium capsules?

Extended phenytoin sodium capsules are a prescription medicine used to treat certain types of seizures called

tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures.

Do not take extended phenytoin sodium capsules if you:

Are allergic to phenytoin or any of the ingredients in extended phenytoin sodium capsules. See the

end of this leaflet for a complete list of ingredients in extended phenytoin sodium capsules.

Have had an allergic reaction to CEREBYX (fosphenytoin), PEGANONE (ethotoin), or

MESANTOIN (mephenytoin).

Have had liver problems from taking phenytoin.

Take delavirdine.

Before taking extended phenytoin sodium capsules, tell your healthcare provider about all of your medical

conditions, including if you:

Have or have had depression, mood problems, or suicidal thoughts or behavior

Have had an allergic reaction to a medicine similar to extended phenytoin sodium capsules called

carboxamides, barbiturates, succinimides, and oxazolidinediones

Have or had liver or kidney problems

Have or had an enzyme problem called porphyria

Have or had high blood sugar (hyperglycemia)

Drink alcohol

Are pregnant or plan to become pregnant. Extended phenytoin sodium capsules may harm your

unborn baby.

If you take extended phenytoin sodium capsules during pregnancy, your baby is at risk for

serious birth defects.

If you become pregnant while taking extended phenytoin sodium capsules, the level of

phenytoin in your blood may decrease, causing your seizures to become worse. Your

healthcare provider may change your dose of phenytoin.

If you take extended phenytoin sodium capsules during pregnancy, your baby is also at risk

for bleeding problems right after birth. Your healthcare provider may give you and your baby

medicine to prevent this.

All women of child-bearing age should talk to their healthcare provider about using other

possible treatments instead of extended phenytoin sodium capsules.

If you are of childbearing age and are not planning on getting pregnant, you should use

effective birth control (contraception) while taking extended phenytoin sodium capsules.

Pregnancy Registry: If you become pregnant while taking extended phenytoin sodium

capsules, talk to your healthcare provider about registering with the North American

Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-

2334. The purpose of this registry is to collect information about the safety of antiepileptic

drugs during pregnancy.

Are breastfeeding or plan to breastfeed. Extended phenytoin sodium capsules can pass into breast

milk. You and your healthcare provider should decide if you will take extended phenytoin sodium

capsules while you are breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter

medicines, vitamins, and herbal supplements. These medicines can change the levels of phenytoin in your

blood.

Taking extended phenytoin sodium capsules with certain other medicines can cause side effects or affect

how well they work. Do not start or stop other medicines without talking to your healthcare provider.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist

when you get a new medicine.

How should I take extended phenytoin sodium capsules?

Take extended phenytoin sodium capsules exactly as your healthcare provider tells you.

Your healthcare provider will tell you how much extended phenytoin sodium capsules to take and

when to take it.

Your healthcare provider may change your dose if needed. Do not change your dose of extended

phenytoin sodium capsules without talking to your healthcare provider.

If your healthcare provider has prescribed phenytoin oral suspension, ask your pharmacist for a

medicine dropper or medicine cup to help you measure the correct amount of phenytoin. Do not use a

household teaspoon. Ask your pharmacist for instructions on how to use the measuring device the

right way.

Do not stop taking extended phenytoin sodium capsules without first talking to your healthcare

provider. Stopping extended phenytoin sodium capsules suddenly can cause serious problems.

What should I avoid while taking extended phenytoin sodium capsules?

Do not drink alcohol while you take phenytoin without first talking to your healthcare provider.

Drinking alcohol while taking phenytoin may change your blood levels of phenytoin which can cause

serious problems.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

phenytoin affects you. Phenytoin can slow your thinking and motor skills.

What are the possible side effects of extended phenytoin sodium capsules?

See " What is the most important information I should know about extended phenytoin sodium capsules?"

Extended phenytoin sodium capsules may cause other serious side effects including:

Liver problems.

Low blood count which could increase your chance of getting infections, bruising, bleeding and

increased fatigue.

Softening of your bones (osteopenia, osteoporosis, and osteomalacia) can cause your bones to break

(fractures).

High blood sugar (hyperglycemia).

High levels of extended phenytoin sodium capsules in your blood that could cause confusion also

known as delirium, psychosis or a more serious condition that affects how your brain works

(encephalopathy).

Call your healthcare provider right away, if you have any of the symptoms listed above.

The most common side effects of extended phenytoin sodium capsules include:

Irregular movement of the eye (nystagmus)

Problems with movement and balance (ataxia)

Slurred speech

Decrease in coordination

Drowsiness (somnolence)

Confusion

Extended phenytoin sodium capsules can cause overgrowth of your gums. Brushing and flossing your teeth

and seeing a dentist regularly while taking extended phenytoin sodium capsules can help prevent this from

happening.

These are not all of the possible side effects of extended phenytoin sodium capsules.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-

1088.

How should I store extended phenytoin sodium capsules?

Store extended phenytoin sodium capsules at room temperature between 68° to 77°F (20° to 25°C).

Store in tight, light-resistant containers.

Protect from moisture.

Keep extended phenytoin sodium capsules and all medicines out of the reach of children.

General information about the safe and effective use of extended phenytoin sodium capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use

extended phenytoin sodium capsules for a condition for which it was not prescribed. Do not give extended

phenytoin sodium capsules to other people, even if they have the same symptoms that you have. It may harm

them. You can ask your pharmacist or healthcare provider for information about extended phenytoin sodium

capsules that is written for health professionals.

What are the ingredients in extended phenytoin sodium capsules?

Extended phenytoin sodium capsules USP, 100 mg: Each capsule contains a white to off-white powder.

Capsule is imprinted "TARO PHN 100" in black ink on both body and cap.

Active ingredient: 100 mg phenytoin sodium, USP

Inactive ingredients: confectioner's sugar, hypromellose, lactose monohydrate, magnesium stearate, and talc.

The capsule shell contains benzyl alcohol, black ink, butylparaben, D&C Yellow #10, edetate calcium

disodium, FD&C Red #3, gelatin, methylparaben, propylparaben, sodium lauryl sulfate, sodium propionate,

and titanium dioxide.

Trademarks are the property of their respective owners.

Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761

Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532

For more information about Extended Phenytoin Sodium Capsules, USP call Taro Pharmaceuticals U.S.A.,

Inc., at 1-866-923-4914.

Revised: April 2019

71074-0419-11

Revised: 9/2019

Document Id: 9228d525-a629-2702-e053-2a95a90a656f

34391-3

Set id: 844a16db-17d5-44da-819d-54f3e19cfec2

Version: 1

Effective Time: 20190909

REMEDYREPACK INC.

PHENYTOIN SODIUM- phenytoin sodium capsule, extended release

REMEDYREPACK INC.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use EXTENDED PHENYTOIN SODIUM

CAPSULES safely and effectively. See full prescribing information for EXTENDED PHENYTOIN SODIUM

CAPSULES.

EXTENDED PHENYTOIN SODIUM capsules, for oral use

Initial U.S. Approval: 1953

RECENT MAJOR CHANGES

Warnings and Precautions ( 5.6)

10/2018

INDICATIONS AND USAGE

Extended phenytoin sodium capsules are indicated for the treatment of tonic-clonic (grand mal) and psychomotor

(temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. ( 1)

DOSAGE AND ADMINISTRATION

Adult starting dose in patients who have received no previous treatment is one 100 mg extended phenytoin sodium

capsule three times a day, with dose adjustments as necessary. For most adults, the satisfactory maintenance dose will

be one capsule three to four times a day. An increase, up to two capsules three times a day may be made, if necessary.

( 2.1)

Adult once-a-day dose: 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. ( 2.1)

Adult loading dose: reserved for patients in a clinic or hospital setting who require rapid steady-state serum levels and

where intravenous administration is not desired. Refer to full prescribing information. ( 2.1)

Pediatric starting dose is 5 mg/kg/day in two to three equally divided doses, with dosage adjustments as necessary, up

to a maximum of 300 mg daily. Maintenance dosage is 4 mg/kg/day to 8 mg/kg/day. ( 2.2)

Serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum

total concentration is 10 mcg/mL to 20 mcg/mL (unbound phenytoin concentration is 1 mcg/mL to 2 mcg/mL). ( 2.3)

DOSAGE FORMS AND STRENGTHS

Extended phenytoin sodium capsules are available as 100 mg extended phenytoin sodium capsules. ( 3)

CONTRAINDICATIONS

Hypersensitivity to phenytoin, its ingredients, or other hydantoins ( 4, 5.5)

A history of prior acute hepatotoxicity attributable to phenytoin ( 4, 5.7)

Coadministration with delavirdine ( 4)

WARNINGS AND PRECAUTIONS

Withdrawal Precipitated Seizure: May precipitate status epilepticus. Dose reductions or discontinuation should be done

gradually. ( 5.1)

Suicidal Behavior and Ideation: Monitor patients for the emergence or worsening of depression, suicidal thoughts or

behavior, and/or any unusual changes in mood or behavior. ( 5.2)

Serious Dermatologic Reactions: Discontinue extended phenytoin sodium capsules at the first sign of a rash, unless the

rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and

alternative therapy should be considered. ( 5.3)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: If signs or symptoms of

hypersensitivity are present, evaluate the patient immediately. Discontinue if an alternative etiology cannot be

established. ( 5.4)

Cardiac Effects: Bradycardia and cardiac arrest have been reported. ( 5.6)

Hepatic Injury: Cases of acute hepatotoxicity have been reported with extended phenytoin sodium capsules. If this

occurs, immediately discontinue. ( 4, 5.7)

Hematopoietic Complications: If occurs, follow-up observation is indicated and an alternative antiepileptic treatment

should be used. ( 5.8)

ADVERSE REACTIONS

The most common adverse reactions are nervous system reactions, including nystagmus, ataxia, slurred speech,

decreased coordination, somnolence, and mental confusion. ( 6)

To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914

or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Multiple drug interactions because of extensive plasma protein binding, saturable metabolism and potent induction of

hepatic enzymes. ( 7.1, 7.2)

USE IN SPECIFIC POPULATIONS

Pregnancy: Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse

developmental outcomes. ( 5.12, 8.1)

Renal and/or Hepatic Impairment or Hypoalbuminemia: Monitor unbound phenytoin concentrations in these patients. (

8.6)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 9/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Adult Dosage

2.2 Pediatric Dosage

2.3 Dosage Adjustments

2.4 Switching Between Phenytoin Formulations

2.5 Dosing in Patients with Renal or Hepatic Impairment or Hypoalbuminemia

2.6 Geriatric Dosage

2.7 Dosing during Pregnancy

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Withdrawal Precipitated Seizure, Status Epilepticus

5.2 Suicidal Behavior and Ideation

5.3 Serious Dermatologic Reactions

5.4 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

5.5 Hypersensitivity

5.6 Cardiac Effects

5.7 Hepatic Injury

5.8 Hematopoietic Complications

5.9 Effects on Vitamin D and Bone

5.10 Renal or Hepatic Impairment or Hypoalbuminemia

5.11 Exacerbation of Porphyria

5.12 Teratogenicity and Other Harm to the Newborn

5.13 Slow Metabolizers of Phenytoin

5.14 Hyperglycemia

5.15 Serum Phenytoin Levels above Therapeutic Range

6 ADVERSE REACTIONS

7 DRUG INTERACTIONS

7.1 Drugs that Affect Phenytoin Concentrations

7.2 Drugs Affected by Phenytoin

7.3 Drug Enteral Feeding/Nutritional Preparations Interaction

7.4 Drug/Laboratory Test Interactions

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal and/or Hepatic Impairment or Hypoalbuminemia

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage and Handling

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Extended phenytoin sodium capsules, USP are indicated for the treatment of tonic-clonic (grand mal) and

psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or

following neurosurgery.

2 DOSAGE AND ADMINISTRATION

2.1 Adult Dosage

Divided daily dosage:

The recommended starting dose for adult patients who have received no previous treatment is one 100-

mg extended phenytoin sodium capsule, USP by mouth three times daily. Adjust the dosage to suit

individual requirements up to a maximum of two capsules three times a day. For most adults, the

satisfactory maintenance dosage will be one capsule three to four times a day.

Once-a-day dosage:

In adults, if seizure control is established with divided doses of three 100-mg extended phenytoin

sodium capsules, USP daily, once-a-day dosage with 300 mg of extended phenytoin sodium capsules,

USP may be considered. Studies comparing divided doses of 300 mg with a single daily dose of this

quantity indicated absorption, peak serum 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, USP 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

Sections or subsections omitted from the full prescribing information are not listed.

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 extended phenytoin sodium capsules, USP is divided into three doses

(400 mg, 300 mg, 300 mg) and administered at two-hour intervals. Normal maintenance dosage is then

instituted 24 hours after the loading dose, with frequent serum level determinations.

2.2 Pediatric Dosage

The recommended starting dosage for pediatric patients is 5 mg/kg/day by mouth in two or three equally

divided doses, with subsequent dosage individualized to a maximum of 300 mg daily in divided doses.

A recommended daily maintenance dosage is usually 4 mg/kg/day to 8 mg/kg/day in equally divided

doses. Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day).

2.3 Dosage Adjustments

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level

determinations may be necessary for optimal dosage adjustments. Trough levels provide information

about clinically effective serum level range and confirm patient compliance, and are obtained just prior

to the patient's next scheduled dose. Peak levels indicate an individual's threshold for emergence of

dose-related side effects and are obtained at the time of expected peak concentration. Therapeutic

effect without clinical signs of toxicity occurs more often with serum total concentrations between 10

mcg/mL and 20 mcg/mL (unbound phenytoin concentrations between 1 mcg/mL and 2 mcg/mL), although

some mild cases of tonic-clonic (grand mal) epilepsy may be controlled with lower serum levels of

phenytoin. In patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of

unbound phenytoin concentrations may be more relevant [see Dosage and Administration (2.5)].

With recommended dosage, a period of seven to ten 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 seven to ten days.

2.4 Switching Between Phenytoin Formulations

The free acid form of phenytoin is used in phenytoin oral suspension and phenytoin chewable tablets.

Extended phenytoin sodium capsules and parenteral phenytoin 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.

2.5 Dosing in Patients with Renal or Hepatic Impairment or Hypoalbuminemia

Because the fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in

those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound

fraction in those patients [see Warnings and Precautions (5.10) and Use in Specific Populations (8.6)] .

2.6 Geriatric Dosage

Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be

required [see Clinical Pharmacology (12.3)] .

2.7 Dosing during Pregnancy

Decreased serum concentrations of phenytoin may occur during pregnancy because of altered phenytoin

pharmacokinetics. Periodic measurement of serum phenytoin concentrations should be performed during

pregnancy, and the extended phenytoin sodium capsule dosage should be adjusted as necessary.

Postpartum restoration of the original dosage will probably be indicated [see Use in Specific Populations

(8.1)]. Because of potential changes in protein binding during pregnancy, the monitoring of phenytoin

serum levels should be based on the unbound fraction.

3 DOSAGE FORMS AND STRENGTHS

Extended phenytoin sodium capsules, USP are available as:

100 mg: hard, gelatin capsules No. 3 with an opaque orange body and cap containing a white to off-

white powder. Capsule is imprinted "TARO PHN 100" in black ink on both body and cap.

4 CONTRAINDICATIONS

Extended phenytoin sodium capsules are contraindicated in patients with:

A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see Warnings

and Precautions (5.5)] .

A history of prior acute hepatotoxicity attributable to phenytoin [see Warnings and Precautions

(5.7)].

Coadministration with delavirdine because of the potential for loss of virologic response and

possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.

5 WARNINGS AND PRECAUTIONS

5.1 Withdrawal Precipitated Seizure, Status Epilepticus

Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When, in the

judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative

anticonvulsant medication arises, this should be done gradually. However, in the event of an allergic or

hypersensitivity reaction, more rapid substitution of alternative therapy may be necessary. In this case,

alternative therapy should be an anticonvulsant drug not belonging to the hydantoin chemical class.

5.2 Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including extended phenytoin sodium capsules, increase the risk of

suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any

AED for any indication should be monitored for the emergence or worsening of depression, suicidal

thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different

AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted

Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to

placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate

of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24%

among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal

thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in

the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about

drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week

after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because

most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or

behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed.

The finding of increased risk with AEDs of varying mechanisms of action and across a range of

indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary

substantially by age (5 years to 100 years) in the clinical trials analyzed.

Table 1 shows absolute and relative risk by indication for all evaluated AEDs.

Table 1 Risk by indication for antiepileptic drugs in the pooled analysis

Indication

Placebo

Patients

with Events

Per 1000

Patients

Drug

Patients with

Events Per

1000

Patients

Relative Risk:

Incidence of

Events in Drug

Patients /Incidence

in Placebo

Patients

Risk Difference:

Additional Drug

Patients with

Events Per 1000

Patients

Epilepsy

Psychiatric 5.7

Other

Total

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in

clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the

epilepsy and psychiatric indications.

Anyone considering prescribing extended phenytoin sodium capsules or any other AED must balance

the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other

illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an

increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during

treatment, the prescriber needs to consider whether the emergence of these symptoms in any given

patient may be related to the illness being treated.

Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal

thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of

the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of

suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported

immediately to healthcare providers.

5.3 Serious Dermatologic Reactions

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and

Stevens-Johnson syndrome (SJS), have been reported with phenytoin treatment. The onset of symptoms

is usually within 28 days, but can occur later. Extended phenytoin sodium capsules should be

discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms

suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered.

If a rash occurs, the patient should be evaluated for signs and symptoms of Drug Reaction with

Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4)] .

Studies in patients of Chinese ancestry have found a strong association between the risk of developing

SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients

using carbamazepine. Limited evidence suggests that HLA-B*1502 may be a risk factor for the

development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with

SJS/TEN, including phenytoin. Consideration should be given to avoiding phenytoin as an alternative

for carbamazepine in patients positive for HLA-B*1502.

The use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate

clinical vigilance and patient management. The role of other possible factors in the development of, and

morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications,

comorbidities, and the level of dermatologic monitoring have not been studied.

5.4 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan

Hypers ens itivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan

hypersensitivity, has been reported in patients taking antiepileptic drugs, including extended phenytoin

sodium capsules. Some of these events have been fatal or life-threatening. DRESS typically, although

not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with

other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis,

or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this

disorder is variable in its expression, other organ systems not noted here may be involved. It is

important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be

present even though rash is not evident. If such signs or symptoms are present, the patient should be

evaluated immediately. Extended phenytoin sodium capsules should be discontinued if an alternative

etiology for the signs or symptoms cannot be established.

5.5 Hypersensitivity

Extended phenytoin sodium capsules and other hydantoins are contraindicated in patients who have

experienced phenytoin hypersensitivity [see Contraindications (4)] . Additionally, consider alternatives

to structurally similar drugs such as carboxamides (e.g., carbamazepine), barbiturates, succinimides, and

oxazolidinediones (e.g., trimethadione) in these same patients. Similarly, if there is a history of

hypersensitivity reactions to these structurally similar drugs in the patient or immediate family members,

consider alternatives to extended phenytoin sodium capsules.

5.6 Cardiac Effects

Cases of bradycardia and cardiac arrest have been reported in phenytoin-treated patients, both at

recommended phenytoin doses and levels, and in association with phenytoin toxicity [see Overdosage

(10)].

Most of the reports of cardiac arrest occurred in patients with underlying cardiac disease.

5.7 Hepatic Injury

Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported

with extended phenytoin sodium capsules. These events may be part of the spectrum of DRESS or may

occur in isolation [see Warnings and Precautions (5.4)] . Other common manifestations include jaundice,

hepatomegaly, elevated serum transaminase levels, leukocytosis, and eosinophilia. The clinical course

of acute phenytoin hepatotoxicity ranges from prompt recovery to fatal outcomes. In these patients with

acute hepatotoxicity, extended phenytoin sodium capsules should be immediately discontinued and not

readministered.

5.8 Hematopoietic Complications

Hematopoietic complications, some fatal, have occasionally been reported in association with

administration of extended phenytoin sodium capsules. These have included thrombocytopenia,

leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow

suppression.

There have been a number of reports suggesting a relationship between phenytoin and the development

of lymphadenopathy (local or generalized) including benign lymph node hyperplasia, pseudolymphoma,

lymphoma, and Hodgkin's disease. Although a cause and effect relationship has not been established, the

occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of

lymph node pathology. Lymph node involvement may occur with or without symptoms and signs of

DRESS [see Warnings and Precautions (5.4)] .

In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every

effort should be made to achieve seizure control using alternative antiepileptic drugs.

5.9 Effects on Vitamin D and Bone

The chronic use of phenytoin in patients with epilepsy has been associated with decreased bone mineral

density (osteopenia, osteoporosis, and osteomalacia) and bone fractures. Phenytoin induces hepatic

metabolizing enzymes. This may enhance the metabolism of vitamin D and decrease vitamin D levels,

which may lead to vitamin D deficiency, hypocalcemia, and hypophosphatemia. Consideration should be

given to screening with bone-related laboratory and radiological tests as appropriate and initiating

treatment plans according to established guidelines.

5.10 Renal or Hepatic Impairment or Hypoalbuminemia

Because the fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in

those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound

fraction in those patients.

5.11 Exacerbation of Porphyria

In view of isolated reports associating phenytoin with exacerbation of porphyria, caution should be

exercised in using this medication in patients suffering from this disease.

5.12 Teratogenicity and Other Harm to the Newborn

Extended phenytoin sodium capsules may cause fetal harm when administered to a pregnant woman.

Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse

developmental outcomes [see Use in Specific Populations (8.1)] .

Increased frequencies of major malformations (such as orofacial clefts and cardiac defects), and

abnormalities characteristic of fetal hydantoin syndrome, including dysmorphic skull and facial features,

nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits, have

been reported among children born to epileptic women who took phenytoin alone or in combination with

other antiepileptic drugs during pregnancy. There have been several reported cases of malignancies,

including neuroblastoma.

A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent

clotting factors may occur in newborns exposed to phenytoin in utero. This drug-induced condition can

be prevented with vitamin K administration to the mother before delivery and to the neonate after birth.

5.13 Slow Metabolizers of Phenytoin

A small percentage of individuals who have been treated with phenytoin have been shown to metabolize

the drug slowly. Slow metabolism may be caused by limited enzyme availability and lack of induction; it

appears to be genetically determined. If early signs of dose-related central nervous system (CNS)

toxicity develop, serum levels should be checked immediately.

5.14 Hyperglycemia

Hyperglycemia, resulting from the drug's inhibitory effects on insulin release, has been reported.

Phenytoin may also raise the serum glucose level in diabetic patients.

5.15 Serum Phenytoin Levels above Therapeutic Range

Serum levels of phenytoin sustained above the therapeutic range may produce confusional states

referred to as "delirium," "psychosis," or "encephalopathy," or rarely irreversible cerebellar

dysfunction and/or cerebellar atrophy. Accordingly, at the first sign of acute toxicity, serum levels

should be immediately checked. Dose reduction of phenytoin therapy is indicated if serum levels are

excessive; if symptoms persist, termination is recommended.

6 ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling:

Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.1)]

Suicidal Behavior and Ideation [see Warnings and Precautions (5.2)]

Serious Dermatologic Reactions [see Warnings and Precautions (5.3)]

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

[see Warnings and Precautions (5.4)]

Hypersensitivity [see Warnings and Precautions (5.5)]

Cardiac Effects [see Warnings and Precautions (5.6)]

Hepatic Injury [see Warnings and Precautions (5.7)]

Hematopoietic Complications [see Warnings and Precautions (5.8)]

Effects on Vitamin D and Bone [see Warnings and Precautions (5.9)]

Exacerbation of Porphyria [see Warnings and Precautions (5.11)]

Teratogenicity and Other Harm to the Newborn [see Warnings and Precautions (5.12)]

Hyperglycemia [see Warnings and Precautions (5.14)]

The following adverse reactions associated with the use of extended phenytoin sodium capsules were

identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily

from a population of uncertain size, it is not always possible to reliably estimate their frequency or

establish a causal relationship to drug exposure.

Body as a Whole: Allergic reactions in the form of rash and rarely more serious forms and DRESS

have been observed [see Warnings and Precautions (5.3, 5.4)] . 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: Acute hepatic failure, toxic hepatitis, liver damage, nausea, vomiting, constipation,

enlargement of the lips, and gingival hyperplasia.

Hematologic and Lymphatic System: Hematopoietic 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 and Precautions

(5.8)] .

Laboratory Test Abnormality: Phenytoin may decrease serum concentrations of thyroid hormone (T4

and T3), sometimes with an accompanying increase in thyroid-stimulating hormone (TSH), but usually in

the absence of clinical hypothyroidism. Phenytoin may also produce lower than normal values for

dexamethasone or metyrapone tests. Phenytoin may cause increased serum levels of glucose [see

Warnings and Precautions (5.14)] , alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).

Nervous System: The most common adverse reactions encountered with phenytoin therapy are nervous

system reactions and are usually dose-related. Reactions include nystagmus, ataxia, slurred speech,

decreased coordination, somnolence, and mental confusion. Dizziness, vertigo, insomnia, transient

nervousness, motor twitchings, paresthesias, 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. Cerebellar atrophy has been

reported, and appears more likely in settings of elevated phenytoin levels and/or long-term phenytoin

use [see Warnings and Precautions (5.15)] .

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

phenytoin therapy.

phenytoin therapy.

Skin and Appendages: 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, Stevens-Johnson syndrome, and toxic epidermal necrolysis

[see Warnings and Precautions (5.3)] . There have also been reports of hypertrichosis.

Special Senses: Altered taste sensation including metallic taste.

Urogenital: Peyronie's disease

7 DRUG INTERACTIONS

Phenytoin is extensively bound to 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. Monitoring of phenytoin serum levels is recommended when a drug interaction is

suspected.

Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes.

7.1 Drugs that Affect Phenytoin Concentrations

Table 2 includes commonly occurring drug interactions that affect phenytoin concentrations. However,

this list is not intended to be inclusive or comprehensive. Individual prescribing information from

relevant drugs should be consulted.

The addition or withdrawal of these agents in patients on phenytoin therapy may require an adjustment of

the phenytoin dose to achieve optimal clinical outcome.

Table 2: Drugs That Affect Phenytoin Concentrations

Interacting Agent

Examples

Drugs that may increase phenytoin serum levels

Antiepileptic drugs

Ethosuximide, felbamate, oxcarbazepine,

methsuximide, topiramate

Azoles

Fluconazole, ketoconazole, itraconazole, miconazole,

voriconazole

Antineoplastic agents Capecitabine, fluorouracil

Antidepressants

Fluoxetine, fluvoxamine, sertraline

Gastric acid reducing

agents

antagonists (cimetidine), omeprazole

Sulfonamides

Sulfamethizole, sulfaphenazole, sulfadiazine,

sulfamethoxazole-trimethoprim

Other

Acute alcohol intake, amiodarone, chloramphenicol,

chlordiazepoxide, disulfiram, estrogen, fluvastatin,

isoniazid, methylphenidate, phenothiazines,

salicylates, ticlopidine, tolbutamide, trazodone,

warfarin

Drugs that may decrease phenytoin serum levels

Antacids

Calcium carbonate, aluminum hydroxide, magnesium

hydroxide

Prevention or Management: Phenytoin and antacids

should not be taken at the same time of day

Antineoplastic agents

usually in combination

Bleomycin, carboplatin, cisplatin, doxorubicin,

methotrexate

Antiviral agents

Fosamprenavir, nelfinavir, ritonavir

Antiepileptic drugs

Carbamazepine, vigabatrin

Other

Chronic alcohol abuse, diazepam, diazoxide, folic

acid, reserpine, rifampin, St. John's wort

, sucralfate,

theophylline

Drugs that may either increase or decrease phenytoin serum levels

Antiepileptic drugs

Phenobarbital, valproate sodium, valproic acid

7.2 Drugs Affected by Phenytoin

Table 3 includes commonly occurring drug interactions affected by phenytoin. However, this list is not

intended to be inclusive or comprehensive. Individual drug package inserts should be consulted. 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.

Table 3: Drugs Affected by Phenytoin

Interacting Agent Examples

Drugs whose efficacy is impaired by phenytoin

Azoles

Fluconazole, ketoconazole, itraconazole, posaconazole,

voriconazole

Antineoplastic

agents

Irinotecan, paclitaxel, teniposide

Delavirdine

Phenytoin can substantially reduce the concentrations of

delavirdine. This can lead to loss of virologic response

and possible resistance [see Contraindications (4)].

Neuromuscular

blocking agents

Cisatracurium, pancuronium, rocuronium and vecuronium:

resistance to the neuromuscular blocking action of the

nondepolarizing neuromuscular blocking agents has

occurred in patients chronically administered phenytoin.

Whether or not phenytoin has the same effect on other

non-depolarizing agents is unknown.

Prevention or Management: Patients should be monitored

closely for more rapid recovery from neuromuscular

blockade than expected, and infusion rate requirements

may be higher.

Warfarin

Increased and decreased PT/INR responses have been

reported when phenytoin is coadministered with warfarin

Other

Corticosteroids, doxycycline, estrogens, furosemide,

oral contraceptives, paroxetine, quinidine, rifampin,

sertraline, theophylline, and vitamin D

Drugs whose level is decreased by phenytoin

Antiepileptic

drugs

Carbamazepine, felbamate, lamotrigine, topiramate,

oxcarbazepine

Antilipidemic

agents

Atorvastatin, fluvastatin, simvastatin

Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir,

Antacids may affect absorption of phenytoin.

The induction potency of St. John's wort may vary widely based on preparation.

Antiviral agents

ritonavir, saquinavir

Fosamprenavir: 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

Calcium channel

blockers

Nifedipine, nimodipine, nisoldipine, verapamil

Other

Albendazole (decreases active metabolite),

chlorpropamide, clozapine, cyclosporine, digoxin,

disopyramide, folic acid, methadone, mexiletine,

praziquantel, quetiapine

7.3 Drug Enteral Feeding/Nutritional Preparations Interaction

Literature reports suggest that patients who have received enteral feeding preparations and/or related

nutritional supplements have lower than expected phenytoin serum levels. It is therefore suggested that

phenytoin not be administered concomitantly with an enteral feeding preparation. More frequent serum

phenytoin level monitoring may be necessary in these patients.

7.4 Drug/Laboratory Test Interactions

Care should be taken when using immunoanalytical methods to measure serum phenytoin concentrations.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to

antiepileptic drugs (AEDs), such as extended phenytoin sodium capsules, during pregnancy. Physicians

are advised to recommend that pregnant patients taking extended phenytoin sodium capsules enroll in the

North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll

free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can

also be found at the website http://www.aedpregnancyregistry.org/

Risk Summary

In humans, prenatal exposure to phenytoin may increase the risks for congenital malformations and other

adverse developmental outcomes. Prenatal phenytoin exposure is associated with an increased

incidence of major malformations, including orofacial clefts and cardiac defects. In addition, the fetal

hydantoin syndrome, a pattern of abnormalities including dysmorphic skull and facial features, nail and

digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits has been

reported among children born to epileptic women who took phenytoin alone or in combination with

other antiepileptic drugs during pregnancy [see Data] . There have been several reported cases of

malignancies, including neuroblastoma, in children whose mothers received phenytoin during

pregnancy.

Administration of phenytoin to pregnant animals resulted in an increased incidence of fetal

malformations and other manifestations of developmental toxicity (including embryofetal death, growth

impairment, and behavioral abnormalities) in multiple species at clinically relevant doses [see Data].

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage

in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk

The effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum

levels is unpredictable

in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk

of major birth defects and miscarriage for the indicated population is unknown.

Clinical Considerations

Disease-associated maternal risk

An increase in seizure frequency may occur during pregnancy because of altered phenytoin

pharmacokinetics. Periodic measurement of serum phenytoin concentrations may be valuable in the

management of pregnant women as a guide to appropriate adjustment of dosage [see Dosage and

Administration (2.3, 2.7)] . However, postpartum restoration of the original dosage will probably be

indicated [see Clinical Pharmacology (12.3)].

Fetal/Neonatal Adverse Reactions

A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent

clotting factors may occur in newborns exposed to phenytoin in utero. This drug-induced condition can

be prevented with vitamin K administration to the mother before delivery and to the neonate after birth.

Data

Human Data

Meta-analyses using data from published observational studies and registries have estimated an

approximately 2.4-fold increased risk for any major malformation in children with prenatal phenytoin

exposure compared to controls. An increased risk of heart defects, facial clefts, and digital hypoplasia

has been reported. The fetal hydantoin syndrome is a pattern of congenital anomalies including

craniofacial anomalies, nail and digital hypoplasia, prenatal-onset growth deficiency, and

neurodevelopmental deficiencies.

Animal data

Administration of phenytoin to pregnant rats, rabbits, and mice during organogenesis resulted in

embryofetal death, fetal malformations, and decreased fetal growth. Malformations (including

craniofacial, cardiovascular, neural, limb, and digit abnormalities) were observed in rats, rabbits, and

mice at doses as low as 100 mg/kg, 75 mg/kg, and 12.5 mg/kg, respectively.

8.2 Lactation

Risk Summary

Phenytoin is secreted in human milk. The developmental and health benefits of breastfeeding should be

considered along with the mother's clinical need for extended phenytoin sodium capsules and any

potential adverse effects on the breastfed infant from extended phenytoin sodium capsules or from the

underlying maternal condition.

8.4 Pediatric Use

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 mg/kg to 8 mg/kg.

Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day) [see Dosage

and Administration (2.2)] .

8.5 Geriatric Use

Phenytoin clearance tends to decrease with increasing age [see Clinical Pharmacology (12.3)] . Lower

or less frequent dosing may be required [see Dosage and Administration (2.6)] .

8.6 Renal and/or Hepatic Impairment or Hypoalbuminemia

The liver is the chief site of biotransformation of phenytoin; patients with impaired liver function,

elderly patients, or those who are gravely ill may show early signs of toxicity.

Because the fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in

those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound

fraction in those patients.

10 OVERDOSAGE

The lethal dose in pediatric patients is not known. The lethal dose in adults is estimated to be 2 grams to

5 grams. The initial symptoms are nystagmus, ataxia, and dysarthria. Other signs are tremor,

hyperreflexia, lethargy, slurred speech, blurred vision, nausea, and vomiting. The patient may become

comatose and hypotensive. Bradycardia and cardiac arrest have been reported [see Warnings and

Precautions (5.6)] . Death is caused by respiratory and circulatory depression.

There are marked variations among individuals with respect to phenytoin serum levels where toxicity

may occur. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL; dysarthria

and lethargy appear when the serum concentration is over 40 mcg/mL, but as high a concentration as 50

mcg/mL has been reported without evidence of toxicity. As much as 25 times the therapeutic dose has

been taken to result in a serum concentration over 100 mcg/mL with complete recovery. Irreversible

cerebellar dysfunction and atrophy have been reported.

Treatment: Treatment is nonspecific since there is no known antidote.

The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate

supportive measures employed. Hemodialysis can be considered since phenytoin is not completely

bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe

intoxication in pediatric patients.

In acute overdosage the possibility of other CNS depressants, including alcohol, should be borne in

mind.

11 DESCRIPTION

Extended phenytoin sodium capsules, USP are related to the barbiturates in chemical structure, but has a

five-membered ring. The chemical name is 5,5-diphenyl-2,4 imidazolidinedione, having the following

structural formula:

Each extended phenytoin sodium capsule, USP contains 100 mg phenytoin sodium, USP. Also contains

confectioner's sugar, hypromellose, lactose monohydrate, magnesium stearate, and talc. The capsule

shell contains benzyl alcohol, black ink, butylparaben, D&C Yellow #10, edetate calcium disodium,

FD&C Red #3, gelatin, methylparaben, propylparaben, sodium lauryl sulfate, sodium propionate, and

titanium dioxide. Product in vivo performance 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.

Meets USP Dissolution Test 2.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is

thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a

reduction in sustained high-frequency neuronal discharges.

12.3 Pharmacokinetics

Absorption

For extended phenytoin sodium capsules, peak serum levels occur 4 to 12 hours after administration.

Steady-state therapeutic levels are achieved at least 7 to 10 days (5 to 7 half-lives) after initiation of

therapy with recommended doses of 300 mg/day. When serum level determinations are necessary, they

should be obtained at least 5 to 7 half-lives after treatment initiation, dosage change, or addition or

subtraction of another drug to the regimen so that equilibrium or steady-state will have been achieved.

Distribution

Phenytoin is extensively bound to serum plasma proteins.

Elimination

The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7

to 42 hours.

Metabolism

Phenytoin is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19. Because

phenytoin is hydroxylated in the liver by an enzyme system which is saturable at high serum levels,

small incremental doses may increase the half-life and produce very substantial increases in serum

levels, when these are in the upper range. The steady-state level may be disproportionately increased,

with resultant intoxication, from an increase in dosage of 10% or more.

In most patients maintained at a steady dosage, stable phenytoin serum levels are achieved. There may be

wide interpatient variability in phenytoin serum levels with equivalent dosages. Patients with unusually

low levels may be noncompliant or hypermetabolizers of phenytoin. Unusually high levels result from

liver disease, variant CYP2C9 and CYP2C19 alleles, or drug interactions which result in metabolic

interference. The patient with large variations in phenytoin serum levels, despite standard doses,

presents a difficult clinical problem. Serum level determinations in such patients may be particularly

helpful. As phenytoin is highly protein bound, free phenytoin levels may be altered in patients whose

protein binding characteristics differ from normal.

Excretion

Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the

intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly

with glomerular filtration but, more importantly, by tubular secretion.

Specific Populations

Age: Geriatric Population:

Phenytoin clearance tends to decrease with increasing age (20% less in patients over 70 years of age

relative to that in patients 20 to 30 years of age). Since phenytoin clearance is decreased slightly in

elderly patients, lower or less frequent dosing may be required [see Dosage and Administration (2.6)].

Sex/Race:

Gender and race have no significant impact on phenytoin pharmacokinetics.

Renal or Hepatic Impairment:

Increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with

hypoalbuminemia has been reported.

Pregnancy:

It has been reported in the literature that the plasma clearance of phenytoin generally increased during

pregnancy, reached a peak in the third trimester and returned to the level of pre-pregnancy after few

weeks or months of delivery.

Drug Interaction Studies

Phenytoin is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19. Phenytoin is a

potent inducer of hepatic drug-metabolizing enzymes [see Drug Interactions (7.1, 7.2)] .

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis [see Warnings and Precautions (5.7)]

In carcinogenicity studies, phenytoin was administered in the diet to mice (10 mg/kg/day, 25 mg/kg/day,

or 45 mg/kg/day) and rats (25 mg/kg/day, 50 mg/kg/day, or 100 mg/kg/day) for 2 years. The incidences

of hepatocellular tumors were increased in male and female mice at the highest dose. No increases in

tumor incidence were observed in rats. The highest doses tested in these studies were associated with

peak serum phenytoin levels below human therapeutic concentrations.

In carcinogenicity studies reported in the literature, phenytoin was administered in the diet for 2 years at

doses up to 600 ppm (approximately 90 mg/kg/day) to mice and up to 2400 ppm (approximately 120

mg/kg/day) to rats. The incidences of hepatocellular tumors were increased in female mice at all but the

lowest dose tested. No increases in tumor incidence were observed in rats.

Mutagenesis

Phenytoin was negative in the Ames test and in the in vitro clastogenicity assay in Chinese hamster ovary

(CHO) cells.

In studies reported in the literature, phenytoin was negative in the in vitro mouse lymphoma assay and the

in vivo micronucleus assay in mouse. Phenytoin was clastogenic in the in vitro sister chromatid exchange

assay in CHO cells.

Fertility

Phenytoin has not been adequately assessed for effects on male or female fertility.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Extended Phenytoin Sodium Capsules USP, 100 mg are hard gelatin capsules No. 3 with an opaque

orange body and cap, imprinted "TARO PHN 100" in black ink. They are available in:

Bottles of 30

NDC 51672-4111-6

Bottles of 100

NDC 51672-4111-1

Bottles of 1000

NDC 51672-4111-3

Unit Dose of 100's

NDC 51672-4111-0

16.2 Storage and Handling

Store at 20˚ to 25˚C (68˚ to 77˚F) [See USP Controlled Room Temperature]. Preserve in tight, light-

resistant containers. Protect from moisture.

17 PATIENT COUNSELING INFORMATION

Advise patients to read the FDA-approved patient labeling (Medication Guide).

Administration Information

Advise patients taking phenytoin of the importance of adhering strictly to the prescribed dosage

regimen, and of informing the physician of any clinical condition in which it is not possible to take the

drug orally as prescribed, e.g., surgery, etc.

Advise patients not to use capsules which are discolored.

Withdrawal of Antiepileptic Drugs

Advise patients not to discontinue use of extended phenytoin sodium capsules without consulting with

their healthcare provider. Extended phenytoin sodium capsules should normally be gradually withdrawn

to reduce the potential for increased seizure frequency and status epilepticus [see Warnings and

Precautions (5.1)] .

Suicidal Ideation and Behavior

Counsel patients, their caregivers, and families that AEDs, including extended phenytoin sodium

capsules, may increase the risk of suicidal thoughts and behavior and advise them of the need to be alert

for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior,

or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern

should be reported immediately to healthcare providers [see Warnings and Precautions (5.2)] .

Potential Signs of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Other

Systemic Reactions

Advise patients of the early toxic signs and symptoms of potential hematologic, dermatologic,

hypersensitivity, or hepatic reactions. These symptoms may include, but are not limited to, fever, sore

throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy, facial swelling, and petechial or

purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. Advise

the patient that, because these signs and symptoms may signal a serious reaction, that they must report

any occurrence immediately to a physician. In addition, advise the patient that these signs and symptoms

should be reported even if mild or when occurring after extended use [see Warnings and Precautions

(5.3, 5.4, 5.5, 5.7, 5.8)] .

Cardiac Effects

Counsel patients that cases of bradycardia and cardiac arrest have been reported, both at recommended

phenytoin doses and levels, and in association with phenytoin toxicity. Patients should report cardiac

signs or symptoms to their healthcare provider [see Warnings and Precautions (5.6) and Overdosage

(10)].

Effects of Alcohol Use and Other Drugs and Over-the-Counter Drug Interactions

Caution patients against the use of other drugs or alcoholic beverages without first seeking their

physician's advice [Drug Interactions (7.1, 7.2)].

Inform patients that certain over-the-counter medications (e.g., antacids, cimetidine, and omeprazole),

vitamins (e.g., folic acid), and herbal supplements (e.g., St. John's wort) can alter their phenytoin levels.

Hyperglycemia

Advise patients that extended phenytoin sodium capsules may cause an increase in blood glucose levels

[see Warnings and Precautions (5.14)] .

Gingival Hyperplasia

Advise patients of the importance of good dental hygiene in order to minimize the development of

gingival hyperplasia and its complications.

Neurologic Effects

Counsel patients that extended phenytoin sodium capsules may cause dizziness, gait disturbance,

decreased coordination and somnolence. Advise patients taking extended phenytoin sodium capsules not

to drive, operate complex machinery, or engage in other hazardous activities until they have become

accustomed to any such effects associated with extended phenytoin sodium capsules.

Use in Pregnancy

Inform pregnant women and women of childbearing potential that use of extended phenytoin sodium

capsules during pregnancy can cause fetal harm, including an increased risk for cleft lip and/or cleft

palate (oral clefts), cardiac defects, dysmorphic skull and facial features, nail and digit hypoplasia,

growth abnormalities (including microcephaly), and cognitive deficits. When appropriate, counsel

pregnant women and women of childbearing potential about alternative therapeutic options. Advise

women of childbearing potential who are not planning a pregnancy to use effective contraception while

using extended phenytoin sodium capsules, keeping in mind that there is a potential for decreased

hormonal contraceptive efficacy [see Drug Interactions (7.2)].

Instruct patients to notify their physician if they become pregnant or intend to become pregnant during

therapy, and to notify their physician if they are breastfeeding or intend to breastfeed during therapy [see

Use in Specific Populations (8.1, 8.2)] .

Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if

they become pregnant. This registry is collecting information about the safety of antiepileptic drugs

during pregnancy [see Use in Specific Populations (8.1)] .

Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761

Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532

Revised: April 2019

71074-0419-11

MEDICATION GUIDE

Extended Phenytoin (fen ´ i toin) Sodium Capsules, USP

What is the most important information I should know about extended phenytoin sodium

caps ules ?

Do not stop taking extended phenytoin sodium capsules without first talking to your

healthcare provider.

Stopping extended phenytoin sodium capsules suddenly can cause serious problems.

Stopping a seizure medicine suddenly can cause you to have seizures more often or seizures that

will not stop (status epilepticus).

Like other antiepileptic drugs, extended phenytoin sodium capsules may cause suicidal

thoughts or actions in a very small number of people, about 1 in 500. Call a healthcare

provider right away if you have any of these symptoms, especially if they are new, worse, or

worry you:

Thoughts about suicide or dying

Attempts to commit suicide

New or worse depression

New or worse anxiety

Feeling agitated or restless

Panic attacks

Trouble sleeping (insomnia)

New or worse irritability

Acting aggressive, being angry, or violent

Acting on dangerous impulses

An extreme increase in activity and talking

(mania)

Other unusual changes in behavior or mood

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts

or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Extended phenytoin sodium capsules can cause a type of serious allergic reaction that may

affect different parts of the body such as your liver, kidneys, blood, heart, skin or other parts

of your body. These can be very serious and cause death. Call your healthcare provider right

away if you have any or all of these symptoms:

Fever

Rash

Swollen lymph glands

Swelling of your face, eye, lips, or tongue

Trouble swallowing or breathing

Sore throat

Sores in your mouth

Bruise easily

Purple or red spots on your skin

Increase infections

Not wanting to eat (anorexia)

Nausea

Vomiting

Yellowing of the skin and the white part of your

eyes (jaundice)

Call your healthcare provider even if the symptoms are mild or if you have been taking extended

phenytoin sodium capsules for an extended period of time. These symptoms can be a sign of a serious

allergic reaction.

Phenytoin can cause problems with your heart, including a slow heartbeat. Let your

healthcare provider know right away if you have any of these symptoms:

dizziness

tiredness

feeling like your heart is beating slowly or skipping beats

chest pain

What are extended phenytoin sodium capsules?

Extended phenytoin sodium capsules are a prescription medicine used to treat certain types of seizures

called tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures.

Do not take extended phenytoin sodium capsules if you:

Are allergic to phenytoin or any of the ingredients in extended phenytoin sodium capsules. See the

end of this leaflet for a complete list of ingredients in extended phenytoin sodium capsules.

Have had an allergic reaction to CEREBYX (fosphenytoin), PEGANONE (ethotoin), or

MESANTOIN (mephenytoin).

Have had liver problems from taking phenytoin.

Take delavirdine.

Before taking extended phenytoin sodium capsules, tell your healthcare provider about all of

your medical conditions, including if you:

Have or have had depression, mood problems, or suicidal thoughts or behavior

Have had an allergic reaction to a medicine similar to extended phenytoin sodium capsules called

carboxamides, barbiturates, succinimides, and oxazolidinediones

Have or had liver or kidney problems

Have or had an enzyme problem called porphyria

Have or had high blood sugar (hyperglycemia)

Drink alcohol

Are pregnant or plan to become pregnant. Extended phenytoin sodium capsules may harm your

unborn baby.

If you take extended phenytoin sodium capsules during pregnancy, your baby is at risk for

serious birth defects.

If you become pregnant while taking extended phenytoin sodium capsules, the level of phenytoin

in your blood may decrease, causing your seizures to become worse. Your healthcare provider

may change your dose of phenytoin.

If you take extended phenytoin sodium capsules during pregnancy, your baby is also at risk for

bleeding problems right after birth. Your healthcare provider may give you and your baby

medicine to prevent this.

All women of child-bearing age should talk to their healthcare provider about using other

possible treatments instead of extended phenytoin sodium capsules.

If you are of childbearing age and are not planning on getting pregnant, you should use effective

birth control (contraception) while taking extended phenytoin sodium capsules.

Pregnancy Registry: If you become pregnant while taking extended phenytoin sodium capsules,

talk to your healthcare provider about registering with the North American Antiepileptic Drug

Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of

this registry is to collect information about the safety of antiepileptic drugs during pregnancy.

Are breastfeeding or plan to breastfeed. Extended phenytoin sodium capsules can pass into breast

milk. You and your healthcare provider should decide if you will take extended phenytoin sodium

capsules while you are breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-

counter medicines, vitamins, and herbal supplements. These medicines can change the levels of

phenytoin in your blood.

Taking extended phenytoin sodium capsules with certain other medicines can cause side effects or

affect how well they work. Do not start or stop other medicines without talking to your healthcare

provider.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and

pharmacist when you get a new medicine.

How should I take extended phenytoin sodium capsules?

Take extended phenytoin sodium capsules exactly as your healthcare provider tells you.

Your healthcare provider will tell you how much extended phenytoin sodium capsules to take and

when to take it.

Your healthcare provider may change your dose if needed. Do not change your dose of extended

phenytoin sodium capsules without talking to your healthcare provider.

If your healthcare provider has prescribed phenytoin oral suspension, ask your pharmacist for a

medicine dropper or medicine cup to help you measure the correct amount of phenytoin. Do not use

a household teaspoon. Ask your pharmacist for instructions on how to use the measuring device the

right way.

Do not stop taking extended phenytoin sodium capsules without first talking to your healthcare

provider. Stopping extended phenytoin sodium capsules suddenly can cause serious problems.

What should I avoid while taking extended phenytoin sodium capsules?

Do not drink alcohol while you take phenytoin without first talking to your healthcare provider.

Drinking alcohol while taking phenytoin may change your blood levels of phenytoin which can

cause serious problems.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

phenytoin affects you. Phenytoin can slow your thinking and motor skills.

What are the possible side effects of extended phenytoin sodium capsules?

See " What is the most important information I should know about extended phenytoin sodium

caps ules ?"

Extended phenytoin sodium capsules may cause other serious side effects including:

Liver problems.

Low blood count which could increase your chance of getting infections, bruising, bleeding and

increased fatigue.

Softening of your bones (osteopenia, osteoporosis, and osteomalacia) can cause your bones to

break (fractures).

High blood sugar (hyperglycemia).

High levels of extended phenytoin sodium capsules in your blood that could cause confusion also

known as delirium, psychosis or a more serious condition that affects how your brain works

(encephalopathy).

Call your healthcare provider right away, if you have any of the symptoms listed above.

The most common side effects of extended phenytoin sodium capsules include:

Irregular movement of the eye (nystagmus)

Problems with movement and balance (ataxia)

Slurred speech

Decrease in coordination

Drowsiness (somnolence)

Confusion

Extended phenytoin sodium capsules can cause overgrowth of your gums. Brushing and flossing your

teeth and seeing a dentist regularly while taking extended phenytoin sodium capsules can help prevent

this from happening.

These are not all of the possible side effects of extended phenytoin sodium capsules.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088.

How should I store extended phenytoin sodium capsules?

Store extended phenytoin sodium capsules at room temperature between 68° to 77°F (20° to 25°C).

Store in tight, light-resistant containers.

Protect from moisture.

Keep extended phenytoin sodium capsules and all medicines out of the reach of children.

General information about the safe and effective use of extended phenytoin sodium capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use extended phenytoin sodium capsules for a condition for which it was not prescribed. Do not give

extended phenytoin sodium capsules to other people, even if they have the same symptoms that you

have. It may harm them. You can ask your pharmacist or healthcare provider for information about

extended phenytoin sodium capsules that is written for health professionals.

What are the ingredients in extended phenytoin sodium capsules?

Extended phenytoin sodium capsules USP, 100 mg: Each capsule contains a white to off-white

powder. Capsule is imprinted "TARO PHN 100" in black ink on both body and cap.

Active ingredient: 100 mg phenytoin sodium, USP

Inactive ingredients: confectioner's sugar, hypromellose, lactose monohydrate, magnesium stearate,

and talc. The capsule shell contains benzyl alcohol, black ink, butylparaben, D&C Yellow #10, edetate

calcium disodium, FD&C Red #3, gelatin, methylparaben, propylparaben, sodium lauryl sulfate, sodium

propionate, and titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Trademarks are the property of their respective owners.

Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761

Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532

For more information about Extended Phenytoin Sodium Capsules, USP call Taro Pharmaceuticals

U.S.A., Inc., at 1-866-923-4914.

Revised: April 2019

71074-0419-11

DRUG: Phenytoin Sodium

GENERIC: Phenytoin Sodium

DOSAGE: CAPSULE, EXTENDED RELEASE

ADMINSTRATION: ORAL

NDC: 70518-2293-0

COLOR: orange

SHAPE: CAPSULE

SCORE: No score

SIZE: 16 mm

IMPRINT: TARO;PHN;100

PACKAGING: 30 in 1 BLISTER PACK

ACTIVE INGREDIENT(S):

Phenytoin Sodium 100mg in 1

INACTIVE INGREDIENT(S):

D&C Yellow NO. 10

GELATIN, UNSPECIFIED

FD&C Red NO. 3

methylparaben

SODIUM PROPIONATE HYDRATE

edetate calcium disodium

propylparaben

sodium lauryl sulfate

HYPROMELLOSE, UNSPECIFIED

lactose monohydrate

SUCROSE

magnesium stearate

benzyl alcohol

butylparaben

talc

titanium dioxide

PHENYTOIN SODIUM

phenytoin sodium capsule, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:70 518 -229 3(NDC:516 72-4111)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

PHENYTO IN SO DIUM (UNII: 418 2431BJH) (PHENYTOIN - UNII:6 158 TKW0 C5)

PHENYTOIN SODIUM

10 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SUCRO SE (UNII: C151H8 M554)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

TALC (UNII: 7SEV7J4R1U)

BENZYL ALCO HO L (UNII: LKG8 49 4WBH)

BUTYLPARABEN (UNII: 3QPI1U3FV8 )

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

REMEDYREPACK INC.

EDETATE CALCIUM DISO DIUM (UNII: 25IH6 R4SGF)

FD&C RED NO . 3 (UNII: PN2ZH5LOQY)

GELATIN, UNSPECIFIED (UNII: 2G8 6 QN327L)

METHYLPARABEN (UNII: A2I8 C7HI9 T)

PRO PYLPARABEN (UNII: Z8 IX2SC1OH)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

SO DIUM PRO PIO NATE HYDRATE (UNII: DK6 Y9 P42IN)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

Product Characteristics

Color

o range (o paque)

S core

no sco re

S hap e

CAPSULE

S iz e

16 mm

Flavor

Imprint Code

TARO;PHN;10 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date Marketing End Date

1

NDC:70 518 -229 3-0

30 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

0 9 /0 3/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 40 6 8 4

0 9 /0 3/20 19

Labeler -

REMEDYREPACK INC. (829572556)

Revised: 9/2019

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