Phenytoin Sodium

Class: Hydantoins
VA Class: CN400
CAS Number: 57-41-0
Brands: Dilantin, Dilantin Infatabs, Phenytek

• IV Administration Rate


• 
  

  Must be administered IV slowly.^b

  
  


• 
  

  Do not exceed 50 mg/minute in adults.^b

  
  


• 
  

  Do not exceed 1–3 mg/kg per minute in pediatric patients.^b

  
  

REMS:

FDA approved a REMS for phenytoin to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Phenytoin is a hydantoin-derivative anticonvulsant.^b

Uses for Phenytoin Sodium

Tonic-Clonic Seizures

Mainly in the prophylactic management of tonic-clonic (grand mal) seizures with complex symptomatology (psychomotor seizures).^{a b c d}

Partial Seizures

Mainly in the prophylactic management of partial seizures with complex symptomatology (psychomotor and temporal lobe seizures).^{a b c d}

Effective in controlling partial seizures with autonomic symptoms†.^b

Absence (Petit Mal) Seizures

Not recommended for the treatment of pure absence (petit mal) seizures† since the drug may increase the frequency of these seizures; however, may be useful in conjunction with succinimide or oxazolidinedione anticonvulsants in the management of combined absence and tonic-clonic seizures.^b

Neurosurgical Seizures

Prevention and treatment of seizures occurring during and following neurosurgery.^{a b}

Status Epilepticus

Diazepam generally considered the drug of choice for termination of status epilepticus.^b

Alternatively, concurrent IV administration of phenytoin (or fosphenytoin) and diazepam is a treatment of choice for termination of status epilepticus.^{b c}

May be used parenterally, preferably by IV administration, in the treatment of status epilepticus; however, the usefulness of the drug in this condition is limited by the need for slow administration and its slow onset of action. Fosphenytoin is an alternative.^{b c}

Cardiac Arrhythmias

Useful IV in the treatment of ventricular tachycardia† and paroxysmal atrial tachycardia†, particularly when conventional antiarrhythmic agents or cardioversion is ineffective.^b

Useful orally for maintenance therapy in the management of cardiac arrhythmias†.^b

Cardiac Glycoside Intoxication

Drug of choice IV for the treatment of arrhythmias caused by cardiac glycoside intoxication†.^b

Neuropathic Pain

May have beneficial effects in the symptomatic treatment of chronic pain arising from peripheral neuropathic syndromes† (e.g., trigeminal neuralgia†).^b

Phenytoin Sodium Dosage and Administration

General

Seizure Disorders

• 
  

  Carefully and slowly adjust dosage according to individual requirements and response.^b

  
  


• 
  

  When a patient is transferred from phenytoin to another anticonvulsant, gradually reduce the phenytoin dosage over a period of about 1 week while at the same time therapy is instituted with a low dose of the replacement drug.^b

  
  


• 
  

  When phenytoin replaces phenobarbital or any other barbiturate anticonvulsant, reduce the dose of the barbiturate gradually over a period of 1 week to prevent withdrawal symptoms.^b

  
  


• 
  

  Withdraw phenytoin slowly to avoid precipitating seizures or status epilepticus.^b

  
  

Oral Loading-Dose Regimens

• 
  

  Therapeutic serum phenytoin concentrations can be achieved more rapidly (in 2–24 hours) by the use of an oral loading-dose regimen.^b

  
  


• 
  

  Various regimens have been suggested, and clinicians should consult published protocols for information on specific regimens.^b (See Pediatric Patients and also Adults under Dosage for suggested regimen.)

  
  


• 
  

  Reserve oral loading-dose regimens for patients in a clinic or hospital setting where serum phenytoin concentrations can be closely monitored.^b

  
  


• 
  

  Patients with a history of renal or liver disease should not receive an oral loading-dose regimen.^b

  
  

Administration

Phenytoin and its sodium salt are administered orally.^b

Phenytoin sodium also may be administered by direct IV injection for the initial treatment of status epilepticus and for the prophylaxis of seizures during neurosurgery.^b

Phenytoin sodium also has been infused IV† cautiously.^{b d HID} (See Dilution under IV Administration.)

Avoid sub-Q or perivascular injection because of risk of soft tissue irritation and inflammation. Administer IM only as a last resort. (See IM Administration.)

Oral Administration

Only extended phenytoin sodium capsules should be used for once-daily dosing regimens.

When refilling a prescription for a preparation previously labeled as phenytoin sodium capsules, the pharmacist should determine whether the brand has been reformulated, whether the brand is now extended phenytoin sodium capsules or prompt phenytoin sodium capsules, and which one the clinician intends that the patient continue to receive.^b

Monitor serum phenytoin concentrations when a patient is switched from extended phenytoin sodium capsules to prompt phenytoin sodium capsules.^b

Do not use oral formulations containing phenytoin as the base (e.g., suspensions, chewable tablets) for once-daily dosing regimens.^b

Minimize loss of phenytoin oral suspension during oral administration via a nasogastric tube (secondary to adherence to PVC tubing) by diluting (e.g., threefold) the suspension with a compatible diluent (e.g., sterile water, 5% dextrose, 0.9% sodium chloride) prior to administration, combined with flushing the tube with at least 20 mL of diluent after administration.^b

IV Administration

Inject IV preferably directly into a large vein through a large-gauge needle or IV catheter.^b

Following IV injection, inject 0.9% sodium chloride injection through the same needle or catheter to reduce local venous irritation from alkaline solution.^{b HID}

Generally not recommended for use in IV infusions† because of the possibility that precipitation may occur; however, can be infused IV safely provided adequate precautions are taken.^b (See Dilution.)

Dilution

IV infusion† is feasible provided appropriate precautions are taken, such as maintaining an optimal pH (e.g., ≥10 for 1 mg/mL dilutions), using a suitable infusion fluid (i.e., 0.9% sodium chloride injection or lactated Ringer’s), using a sufficiently diluted solution (e.g., <6.7 mg/mL), starting the infusion immediately after preparation and completing administration within a relatively short period, using a 0.22-mcm inline filter, and carefully observing the admixture.^{b d HID}

One suggested technique: Add 1 g to 1 L 0.9% sodium chloride or lactated Ringer’s to provide a concentration of 1 mg/mL; these solutions generally have a pH ≥10 but final pH is not predictable.^{d HID} Infuse IV† with caution; start the infusion immediately after preparation, complete within a relatively short period, and watch closely for possible crystallization.^HID Use a 0.22-mcm inline filter during infusion.^{d HID}

Crystallization generally occurs in more acidic solutions (e.g., dilutions in 5% dextrose), which should not be used.^{e HID} (See Solution Compatibility under Stability.)

Alternatively, fosphenytoin sodium (Cerebyx), a prodrug of phenytoin, can be used for IV infusion.^c

Rate of Administration

Adults: ≤50 mg/minute; preferably ≤25–50 mg/minute.^{b g}

Pediatric patients: ≤1–3 mg/kg per minute; preferably, 0.5–1.5 mg/kg per minute.^{b f g}

Neonates: ≤1–3 mg/kg per minute;^HID preferably ≤0.5 mg/kg per minute.^f

IM Administration

Administer IM only as a last resort because of erratic absorption from IM injection sites.^b

May be of some value for sustaining established therapeutic plasma concentrations when oral administration is not feasible.^b

Information regarding IM administration for >1 week is lacking; consider alternate routes for administering phenytoin (e.g., gastric intubation) when oral administration is not feasible for >1 week.^b

Fosphenytoin sodium can be administered IM for short-term replacement of oral phenytoin.^b

Dosage

Each 100 mg of phenytoin sodium contains approximately 92 mg of phenytoin; consider the difference when switching from the base to its sodium salt or vice versa.^b

Pediatric Patients

Seizure Disorders

Oral

Usual dosage: Initially, 5 mg/kg or 250 mg/m² daily in 2 or 3 equally divided doses; total dosage ≤300 mg daily.^b

Therapeutic serum concentrations achieved more rapidly with a 500- to 600-mg oral loading dose, in divided doses, followed by usual maintenance dosage 24 hours after initiating loading dose.^c

Adjust subsequent dosage carefully and slowly according to the patient’s requirements.^b

Neonates, maintenance dosage: Usually, 3–5 mg/kg daily.^g

Infants 1–12 months of age, maintenance dosage: Usually, 4–8 mg/kg daily.^b

Children 1–11 years of age, maintenance dosage: 4–10 mg/kg daily.^g

Adolescents, 12–17 years of age, maintenance dosage: 4–8 mg/kg daily.^g

Status Epilepticus

IV

15–20 mg/kg, at a rate ≤1–3 mg/kg per minute.^b

Preferably, 10–15 mg/kg, at a usual rate of 0.5–1.5 mg/kg per minute (maximum total dose of 20 mg/kg in 24 hours).^b

Replace parenteral administration with oral therapy as soon as possible.^b

Adults

Seizure Disorders

Prompt-Release preparations

Oral

Usual dosage: Initially, 100 mg 3 times daily.^b

A period of 5–10 days may be required to achieve anticonvulsant effects.^b

Increases to >300 mg daily may lead to markedly increased serum phenytoin concentrations; therefore, adjust dosage above this level carefully and slowly.^b

Therapeutic serum concentrations achieved more rapidly with a 1-g oral loading dose given as 400, 300, and 300 mg at 2-hour intervals, followed by usual maintenance dosage 24 hours after initiating loading dose.^b

Increase daily dosage gradually, if necessary, in increments of 100 mg every 2–4 weeks until desired response is achieved.^b

Dosing at 100 mg 4 times daily may benefit some patients, and others may require dosages up to 200 mg 3 times daily.^b

Optimum daily dose: Varies considerably but usually in the range of 4–7 mg/kg (300–600 mg daily for most adults).^{b g}

IM

Increase the IM dosage by 50% over the previously established oral dosage.^b

First week back on oral therapy, reduce oral dosage to one-half the original oral dosage to avoid drug accumulation resulting from eventual absorption from the IM injection site; monitoring of serum concentrations recommended.^b

Limit IM therapy to 1 week. (See IM Administration under Administration.)

Extended-Release Preparations

Oral

For patients stabilized on a dosage of 100 mg 3 times daily, once-daily dosing with 300 mg as extended phenytoin sodium capsules may be considered.^b

Do not use prompt phenytoin sodium capsules nor oral phenytoin base suspensions or chewable tablets for once-daily dosing.^b

Status Epilepticus

IV

Initially, 10–15 mg/kg, by direct IV administration at a rate ≤50 mg/minute; the initial dose should be followed by IV or oral maintenance doses of 100 mg every 6–8 hours.^b

Preferably, 15–18 mg/kg, at a rate ≤25–50 mg/minute (maximum total dose of 1.5 g in 24 hours).^{b g}

Oral therapy should replace parenteral administration as soon as possible.^b

Cardiac Arrhythmias

Ventricular Tachycardia

Oral

100 mg 2–4 times daily.^b

IV

100 mg by direct IV injection at 5-minute intervals until the arrhythmia is abolished or undesirable effects appear or until a total of 1 g is given.^b

Paroxysmal Atrial Tachycardia

Oral

100 mg 2–4 times daily.^b

IV

100 mg by direct IV injection at 5-minute intervals until the arrhythmia is abolished or undesirable effects appear or until a total of 1 g is given.^b

Cardiac Glycoside Intoxication

Oral

100 mg 2–4 times daily.^b

IV

100 mg by direct IV injection at 5-minute intervals until the arrhythmia is abolished or undesirable effects appear or until a total of 1 g is given.^b

Prescribing Limits

Pediatric Patients

Seizure Disorders

Oral

Total dosage should not exceed 300 mg daily.^b

Status Epilepticus

IV

Maximum total dose of 20 mg/kg in 24 hours.^b

Adults

Seizure Disorders

Prompt-Release Preparations

Oral

Increases in dosage to >300 mg daily may lead to markedly increased serum phenytoin concentrations; therefore, adjust dosage above this level carefully and slowly.^b

IM

Generally limit IM therapy to 1 week. (See IM Administration under Administration.)

The first week back on oral therapy, reduce the oral dosage to one-half the original oral dosage to avoid drug accumulation resulting from eventual absorption from the IM injection site; monitor serum concentrations.^b

Status Epilepticus

IV

Maximum total dose of 1.5 g in 24 hours.^b

Cardiac Arrhythmias

Ventricular Tachycardia

IV

Maximum total IV dose of 1 g.^b

Paroxysmal Atrial Tachycardia

IV

Maximum total IV dose of 1 g.^b

Cardiac Glycoside Intoxication

IV

Maximum IV dose of 1 g.^b Do not use oral loading-dose regimens.^b

Special Populations

Hepatic Impairment

Consider reduced maintenance dosage in hepatic cirrhosis.^g Do not use oral loading-dose regimens.^b

Renal Impairment

Do not use oral loading-dose regimens.^b

End-stage renal impairment generally can receive usual loading and maintenance dosages initially, adjusting as necessary.^g

Geriatric Patients

May show early signs of toxicity.^a

Geriatric patients with heart disease: It has been recommended that the drug be given at a rate of 50 mg over 2–3 minutes.^b

Obese Patients

Ideal or nonobese weight probably correlates best with maintenance dosages.^g Loading doses may require adjustment for increased volume of distribution.^g

Pregnancy

Monitor phenytoin therapy closely (phenytoin concentrations may decline) to ensure optimum seizure control.^{g h}

Cautions for Phenytoin Sodium

Contraindications

• 
  

  IV use contraindicated in patients with sinus bradycardia, SA block, second- or third-degree AV block, or Adams-Stokes syndrome.^b

  
  


• 
  

  Known hypersensitivity to phenytoin or any ingredient in the respective formulation or to other hydantoins.^b

  
  

Warnings/Precautions

Warnings

Shares the toxic potentials of the hydantoin-derivative anticonvulsants, and the usual precautions of anticonvulsant therapy should be observed.^{b c}

Withdrawal

Abrupt withdrawal can precipitate status epilepticus.^a Reduce dosage or substitute other anticonvulsants cautiously and slowly.^{a b}

Porphyria

May exacerbate porphyria; use with caution.^b

Lymphadenopathy

If lymphadenopathy occurs, differentiate the condition from other types of lymph node pathology and observe the patient closely for an extended period; use alternative anticonvulsants, if possible, for seizure control.^b

IM Injection

Not recommended IM for status epilepticus because of delayed and unpredictable blood concentrations.^b

Cardiovascular Effects

Hypotension if administered too rapidly IV.^b

May cause severe, potentially life-threatening cardiotoxic reactions (e.g., decreased cardiac output, atrial or ventricular conduction depression, ventricular depression).^b IV, may be due in part to propylene glycol (cardiac depressant) in parenteral formulation.^g

Cardiac and Respiratory Disorders

Administer IV only with extreme caution to patients with respiratory depression, myocardial infarction, frank or impending CHF, or otherwise damaged myocardium, and in patients in whom a sudden change in blood pressure may lead to serious complications (e.g., those with hypotension or severe myocardial insufficiency).^b

Alcohol

Acute alcohol intake may increase serum phenytoin concentrations and chronic alcohol use may decrease serum concentrations.^a

Sensitivity Reactions

Rash

If a rash develops, discontinue phenytoin; do not resume if the rash is exfoliative, purpuric, or bullous or if lupus erythematosus, Stevens-Johnson syndrome, or toxic epidermal necrolysis is suspected.^b

Possible increased risk of developing toxic epidermal necrolysis or Stevens-Johnson syndrome in individuals of Asian ancestry who carry the human leukocyte antigen (HLA)-B*1502 allele.^{103 104 105} FDA is evaluating the relationship between use of phenytoin and serious dermatologic reactions in individuals with the HLA-B*1502 allele.¹⁰³ Screening for presence of HLA-B*1502 allele before initiating phenytoin therapy not recommended at this time.¹⁰³ Phenytoin should not be used as an alternative to carbamazepine in HLA-B*1502-positive patients.¹⁰³

If the rash is morbilliform or scarlatiniform, therapy may be restarted after the rash has completely disappeared; if the rash recurs when phenytoin is restarted, further phenytoin therapy is contraindicated.^b

Structurally Similar Compounds

Caution if using structurally similar compounds (e.g., barbiturates, succinimides, oxazolidinediones) in patients who have experienced phenytoin hypersensitivity.^b

Major Toxicities

Blood Concentrations

Concentrations <25 mcg/mL: Most patients tolerate.^b

Concentrations of 25 mcg/mL: In some patients, are associated with nystagmus, ataxia, and diplopia.^b

Concentrations >30 mcg/mL: Drowsiness and lethargy, and rarely asterixis, may result.^b

Concentrations >50 mcg/mL: Extreme lethargy and, occasionally, comatose states occur.^b

Some patients metabolize phenytoin slowly and thus exhibit signs of toxicity even with low to moderate dosage.^b

IV Phenytoin Toxicity

Most important signs of toxicity associated with the IV use of phenytoin sodium are cardiovascular collapse and/or CNS depression.^b

Hypotension occurs if the drug is administered too rapidly by the IV route.^b

Administer the drug slowly at a rate not exceeding 50 mg/minute to minimize these effects.^b

In geriatric patients with heart disease, it has been recommended that the drug be given at a rate of 50 mg over 2–3 minutes; personnel and equipment should be readily available for administration of artificial respiration since severe complications are most common in geriatric or debilitated patients.^b

General Precautions

Osteomalacia

Has been associated with phenytoin therapy and is thought to be caused by phenytoin’s interference with vitamin D metabolism.

Hyperglycemia

In large doses, may increase blood glucose concentrations resulting in hyperglycemia and glycosuria.^{a b}

Average doses do not regularly elevate blood glucose or increase insulin requirements in diabetic patients, but a few patients have experienced fatal, hyperosmolar, nonketotic coma in which phenytoin may have played at least an accessory etiologic role.^b

Hypertrichosis

Usually confined to extremities but can affect trunk and face and may be irreversible.^b

Slow Metabolizers

A small percentage of individuals who have been treated with phenytoin have been shown to metabolize the drug slowly; this appears to be genetically determined and may be due to limited enzyme availability and lack of induction.^a

Seizures Due to Hypoglycemia or Other Metabolic Causes

Not indicated for seizures due to hypoglycemia or other metabolic causes; appropriate diagnostic procedures should be performed as indicated.^b

Specific Populations

Pregnancy

Category D.^h

Evidence of significant risk of fetal congenital abnormalities, fetal hydantoin syndrome (consisting of prenatal growth deficiency, microcephaly, and mental deficiency), and hemorrhage at birth.^h

Use during pregnancy only when clearly needed;^b risk-to-benefit ratio generally favors continued use during pregnancy in women whose seizure control depends on the drug.^h

In addition to reports of a fetal hydantoin syndrome, there have been rare reports of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy.^b

Because of altered absorption or metabolism of phenytoin during pregnancy, an increased frequency of seizures may occur in pregnant women receiving the drug.^b

If administered during pregnancy, serum phenytoin concentrations should be monitored and dosage adjusted accordingly to the lowest possible level required to control seizures; however, restoration of the patient’s usual dosage will probably be necessary postpartum.^{b h}

Consider monitoring maternal folate concentration and administering supplemental folic acid early in pregnancy or before conception as indicated.^h

Lactation

Distributed into breast milk.^{b h} However, use generally is considered compatible with breast-feeding.^h

Geriatric Use

Liver is the chief site for biotransformation; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.^a

Hepatic Impairment

Liver is the chief site for biotransformation; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.^a

Renal Impairment

In large doses, may increase blood glucose concentrations resulting in hyperglycemia and glycosuria; patients with impaired renal function may be most susceptible to this effect.^{a b}

Common Adverse Effects

Adverse GI effects include nausea and vomiting, constipation, epigastric pain, dysphagia, loss of taste, anorexia, and weight loss.^b Adverse CNS effects include mental confusion, nystagmus, ataxia, blurred vision, diplopia, toxic amblyopia, dizziness, insomnia, transient nervousness, motor twitching, and headache.^b

Phenytoin frequently produces gingival hyperplasia, especially in children, which occasionally is so severe that it may require surgical removal.^b

Interactions for Phenytoin Sodium

Specific Drugs or Laboratory Tests

Drug or Test	Interaction	Comments
Alcohol intake, acute	May increase serum phenytoin concentrationsa
Alcohol intake, chronic	May decrease serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Amiodarone	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Antacids, calcium-containing	Calcium ions interfere with GI absorption of phenytoinb	Ingestion times of phenytoin and antacid preparations containing calcium should be staggered in patients with low serum phenytoin concentrations to prevent absorption problemsb
Anticoagulants, coumarin	Efficacy is impaired by phenytoina
Antidepressants, tricyclic	Antidepressant may precipitate seizures in susceptible patientsa	Phenytoin dosage may need adjustmentb
Carbamazepine	May decrease serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Chloramphenicol	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Chlordiazepoxide	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Corticosteroids	Efficacy is impaired by phenytoina
Diazepam	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Dicumarol	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Disulfiram	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Doxycycline	Efficacy impaired by phenytoina
Estrogens	May increase serum phenytoin concentrationsa Efficacy impaired by phenytoina	Monitor and adjust dosage accordingly Observe for possible decreased estrogen efficacy
Furosemide	Efficacy impaired by phenytoina
H2-Antagonists	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Halothane	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Isoniazid	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Methylphenidate	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Oral contraceptives	Efficacy impaired by phenytoina
Phenobarbital	May increase or decrease serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Phenothiazines	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Quinidine	Efficacy impaired by phenytoina	Monitor and adjust dosage accordingly
Reserpine	May decrease serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Rifampin	Efficacy impaired by phenytoina
Salicylates	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Succinimides	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Sucralfate	May decrease serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Sulfonamides	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Test, alkaline phosphatase, serum	May increase serum alkaline phosphatase concentrations
Test, dexamethasone	Phenytoin may cause slight decreases in urinary 17-hydroxycorticosteroids and 17-ketosteroids while urinary 6-β-hydroxycortisol excretion is increasedb Phenytoin may produce lower than normal values for the dexamethasone test
Test, γ-glutamyl transferase (γ-glutamyltranspeptidase, GGT, GGTP)	Phenytoin may produce increased serumγ-glutamyl transferase (γ-glutamyltranspeptidase, GGT, GGTP) concentrations
Test, metyrapone	Phenytoin may cause slight decreases in urinary 17-hydroxycorticosteroids and 17-ketosteroids while urinary 6-β-hydroxycortisol excretion is increasedb Phenytoin may produce lower than normal values for the metyrapone testsb
Test, protein-bound iodine (PBI)	Patients receiving phenytoin have shown reduced protein-bound iodine (PBI) test values without lowered triiodothyronine (T3) values and without clinical symptoms of hypothyroidism; free thyroxine concentrations may also be decreasedb	The 24-hour I 131 thyroidal uptake is apparently not affected Phenytoin may produce increased resin or red cell T3 uptake valuesb Lowered PBI values do not occur unless phenytoin is administered for 1 week or longer, and altered values persist for 7–10 days after phenytoin is discontinuedb
Theophylline	Efficacy impaired by phenytoina	Monitor and adjust dosage accordingly
Tolbutamide	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Trazodone	May increase serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Valproic acid	May increase or decrease serum phenytoin concentrationsa	Monitor and adjust dosage accordingly
Vitamin D	Efficacy impaired by phenytoina

Phenytoin Sodium Pharmacokinetics

Absorption

Bioavailability

Studies using Dilantin have shown that phenytoin and its sodium salt are usually completely absorbed from the GI tract.^b

Extended phenytoin sodium capsules, peak: 4–12 hours.^b

Extended phenytoin sodium capsules are formulated so that they undergo slower dissolution with more prolonged absorption than prompt phenytoin sodium capsules.^b

Bioavailability may vary enough among oral phenytoin sodium preparations of different manufacturers to result in toxic serum concentrations or a loss of seizure control; this should be considered before dispensing a brand or dosage form, which differs from that currently taken by a patient.^b Consult FDA’s Approved Drug Products and Therapeutic Equivalence Evaluations (Orange Book).

IM: Absorption may be erratic due to precipitation at injection site.^{b g}

Plasma Concentrations

Anticonvulsant effect: 10–20 mcg/mL.^g

Antiarrhythmic effect: 10–20 mcg/mL.^g (See Blood Concentrations under Major Toxicities for other concentrations.)

Prompt phenytoin capsules, peak: 1.5–3 hours.^b

Extended phenytoin sodium, peak: 4–12 hours.^b

Serum concentration determinations: Obtain at least 5–7 half-lives after treatment initiation, change in dosage, or addition or subtraction of another drug to the regimen, so that steady-state drug levels may be achieved.^b

Therapeutic plasma concentrations, oral: Achieved after about 1 week of therapy.^b

Following oral administration, therapeutic plasma concentrations can be obtained more rapidly and maintained by administering an initial oral loading dose.^b

Therapeutic plasma concentrations, IV: Within 1–2 hours.^b

Distribution

Extent

Crosses the placenta.^h

Distributed into breast milk.^{b h}

Plasma Protein Binding

Approximately 95%.^b

Elimination

Metabolism

Oxidation by the liver to an inactive metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH).^b

This metabolism is a saturable process; therefore, small increases in dosage may produce substantial increases in plasma phenytoin concentrations.^b

Elimination Route

Capacity-limited elimination, decreasing with increasing concentration.^g

Inactive metabolite (HPPH) is excreted in urine, mainly as the glucuronide;^b approximately 60–75% of the daily dose is excreted in this form.^b

Half-life

Oral: About 22 hours.^b

IV: Ranges from 10–15 hours.^b

Special Populations

Total plasma phenytoin concentrations are lower in chronic uremic patients than in non-uremic patients, which suggests an altered metabolic disposition of the drug in patients with uremia.^b

Stability

Storage

Oral

Tablets

Tight, light- and moisture-resistant containers at <30°C.^{a b}

Suspension

Tight, light-resistant containers at 20–25°C; avoid freezing.^{b d}

Extended and Prompt Capsules

Tight, light- and moisture-resistant containers at <30°C, although one manufacturer recommends storage of their extended phenytoin sodium capsules (Phenytek) at controlled room temperatures of 15–30°C.^b

Parenteral

Injection

15–30°C; avoid freezing.^b

A precipitate may form if the injection is refrigerated or frozen; however, this will dissolve after warming to room temperature.^b

Slight yellowish discoloration of the injection will not affect potency or efficacy, but the injection should not be used if the solution is not clear or if a precipitate is present.^b

Precipitation of free phenytoin will occur at a pH of ≤11.5.^b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Phenytoin sodium injection is physically and/or chemically incompatible with some drugs, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).^b

Solution Compatibility^HID

Incompatible
Dextrose 5% in sodium chloride 0.9%
Dextrose 5% in water
Fat emulsion 10%, IV
Ringer’s injection, lactated
Sodium chloride 0.45%e HID
Variable
Sodium chloride 0.9%e HID

Drug Compatibility

Admixture CompatibilityHID

Compatible
Verapamil HCl
Incompatible
Amikacin sulfate
Bretylium tosylate
Dobutamine HCl
Lidocaine HCl
Lincomycin HCl
Meperidine HCl
Metaraminol bitartrate
Morphine sulfate
Nitroglycerin
Norepinephrine bitartrate
Pentobarbital sodium
Procaine HCl
Streptomycin sulfate

Y-site CompatibilityHID

Compatible
Esmolol HCl
Famotidine
Fluconazole
Foscarnet sodium
Tacrolimus
Incompatible
Amphotericin B cholesteryl sulfate complex
Cefepime HCI
Ceftazidime
Ciprofloxacin
Clarithromycin
Diltiazem HCl
Enalaprilat
Fenoldopam mesylate
Fentanyl citrate
Heparin sodium
Heparin sodium with hydrocortisone sodium succinate
Hydromorphone HCl
Lansoprazole
Linezolid
Methadone HCl
Morphine sulfate
Potassium chloride
Propofol
Sufentanil citrate
Theophylline
Vitamin B complex with C

Actions

• 
  

  Limitation of seizure propagation by reduction of post-tetanic potentiation (PTP), possibly by reducing the passive influx of sodium ions or by increasing the efficiency of the sodium pump so that excess accumulation of intracellular sodium does not occur during tetanic stimulation.^c

  
  


• 
  

  Loss of PTP also prevents cortical seizure foci from detonating adjacent cortical areas.^c

  
  


• 
  

  Exhibits antiarrhythmic properties similar to those of quinidine or procainamide.^b

  
  


• 
  

  Although little effect on the electrical excitability of cardiac muscle, it decreases the force of contraction, depresses pacemaker action, and improves atrioventricular conduction, particularly when it has been depressed by digitalis glycosides.^b

  
  


• 
  

  Prolongs the effective refractory period relative to the action potential duration.^b

  
  


• 
  

  May produce hypotension following IV administration.^b

  
  


• 
  

  Little hypnotic activity.^b

  
  

Advice to Patients

• 
  

  Importance of cautioning patients not to use other drugs or alcoholic beverages without first seeking the clinician’s advice.^a

  
  


• 
  

  Importance of instructing patients to contact a clinician if skin rash develops.^a

  
  


• 
  

  Importance of stressing good dental hygiene in order to minimize the development of gingival hyperplasia and its complications.^a

  
  


• 
  

  Advise patient of possible development of hypertrichosis and lymphadenopathy.^{a b}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Phenytoin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Suspension	125 mg/5 mL*	Dilantin-125

Midazolam Syrup

Pronunciation: mid-AY-zoe-lam
Generic Name: Midazolam
Brand Name: Generic only. No brands available.

Midazolam Syrup may cause severe breathing problems (eg, respiratory depression, respiratory arrest), especially when used for sedation in noncritical care settings. Risk is increased when other depressants (eg, sedatives, tranquilizers) are also being used. Respiratory depression and respiratory arrest could result in brain damage or death if not treated properly. Midazolam Syrup should only be used under appropriate close medical supervision.

Midazolam Syrup is used for:

Reducing anxiety or producing drowsiness or memory loss in children before certain medical procedures or surgery. It may also be used for other conditions as determined by your doctor.

Midazolam Syrup is a benzodiazepine. It works in the central nervous system (brain) to cause sleepiness, muscle relaxation, and short-term memory loss, and to reduce anxiety.

Do NOT use Midazolam Syrup if:

• you are allergic to any ingredient in Midazolam Syrup or to cherries


• you have acute narrow-angle glaucoma, severe mental problems (eg, psychosis), or severe liver disease


• you have alcohol intoxication with abnormal vital signs


• you are taking delavirdine, efavirenz, an HIV protease inhibitor (eg, ritonavir), or sodium oxybate (GHB)

Contact your doctor or health care provider right away if any of these apply to you.

Video: Treatment for Depression

Treatments for depression are getting better everyday and there are things you can start doing right away.

Before using Midazolam Syrup:

Some medical conditions may interact with Midazolam Syrup. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have lung, airway, or breathing problems (eg, COPD); glaucoma or risk for glaucoma; heart, liver, or kidney problems; the blood disease porphyria; severe depression; myasthenia gravis; or a history of drug abuse or dependence; or if you have consumed alcohol recently


• if you have a severe infection

Some MEDICINES MAY INTERACT with Midazolam Syrup. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Carbamazepine, phenobarbital, phenytoin, rifampin, or St. John's wort because the effectiveness of Midazolam Syrup may be decreased


• Azole antifungals (eg, itraconazole), barbiturate anesthetics (eg, thiopental), calcium channel blockers (eg, diltiazem, verapamil), clozapine, delavirdine, diltiazem, disulfiram, efavirenz, HIV protease inhibitors (eg, ritonavir, saquinavir), ketolides (eg, telithromycin), macrolides (eg, erythromycin), narcotic pain medicines (eg, codeine), nefazodone, omeprazole, sodium oxybate (GHB), or valproic acid because serious side effects, such as low blood pressure, breathing problems, and excessive sedation, may occur


• Hydantoins (eg, phenytoin) because side effects may be increased by Midazolam Syrup

This may not be a complete list of all interactions that may occur. Ask your health care provider if Midazolam Syrup may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Midazolam Syrup:

Use Midazolam Syrup as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Midazolam Syrup is intended for a single use only. You should not use Midazolam Syrup for long-term use.


• Midazolam Syrup is usually administered at your doctor's office, hospital, or clinic. If you are using Midazolam Syrup at home, carefully follow the directions provided by your doctor or other health care provider.


• Avoid eating grapefruit or drinking grapefruit juice while you are taking Midazolam Syrup.


• If you miss a dose of Midazolam Syrup, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Midazolam Syrup.

Important safety information:

• Midazolam Syrup may cause drowsiness, dizziness, or blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until the effects of Midazolam Syrup have disappeared or until the day after you receive Midazolam Syrup, whichever is longer. Using Midazolam Syrup alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Avoid drinking alcohol or taking other medications that cause drowsiness (eg, sedatives, tranquilizers) while using Midazolam Syrup. Midazolam Syrup will add to the effects of alcohol and other depressants. Ask your pharmacist if you have questions about which medicines are depressants.


• Midazolam Syrup can cause partial or complete memory loss for several hours.


• Use of Midazolam Syrup is not recommended in ELDERLY patients. Safety and effectiveness have not been established.


• Caution is advised when using Midazolam Syrup in CHILDREN because they may be more sensitive to its effects.


• Use Midazolam Syrup with extreme caution in CHILDREN younger than 6 months of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Midazolam Syrup has been shown to cause harm to the fetus. If you become pregnant, discuss with your doctor the benefits and risks of using Midazolam Syrup during pregnancy. Midazolam Syrup is not recommended for use during labor and delivery. Midazolam Syrup is excreted in breast milk. If you are or will be breast-feeding while you are using Midazolam Syrup, check with your doctor or pharmacist to discuss the risks to your baby.

When used for long periods of time or at high doses, some people develop a need to continue taking Midazolam Syrup. This is known as DEPENDENCE or addiction.

If you use Midazolam Syrup for long periods of time or at high doses and suddenly stop taking Midazolam Syrup, you may experience WITHDRAWAL symptoms, including fast heartbeat, hallucinations, muscle cramps, seizures, stomach cramps or bloating, sweating, tremor, and vomiting.

Possible side effects of Midazolam Syrup:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dizziness; drowsiness; nausea; short-term memory loss; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation; chest pain; combativeness; hyperactivity; irregular breathing patterns; prolonged drowsiness; skipped heartbeats; slow or fast heartbeat; slow or difficult breathing; seizure; severe dizziness; unusual or involuntary muscle movements or muscle tremor.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Midazolam side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include clumsiness; coma; confusion; deep sleep; loss of consciousness; loss of coordination; severe drowsiness; slow reflexes.

Proper storage of Midazolam Syrup:

Store Midazolam Syrup at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Keep Midazolam Syrup out of the reach of children and away from pets.

General information:

• If you have any questions about Midazolam Syrup, please talk with your doctor, pharmacist, or other health care provider.


• Midazolam Syrup is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Midazolam Syrup. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Midazolam resources

• Midazolam Side Effects (in more detail)
• Midazolam Use in Pregnancy & Breastfeeding
• Midazolam Drug Interactions
• Midazolam Support Group
• 6 Reviews for Midazolam - Add your own review/rating

Compare Midazolam with other medications

• ICU Agitation
• Light Anesthesia
• Light Sedation

Metastron

Generic Name: strontium chloride sr 89 (Intravenous route, Injection route)

STRON-shee-um KLOR-ide Sr 89

Commonly used brand name(s)

In the U.S.

• Metastron

Available Dosage Forms:

• Injectable


• Solution

Therapeutic Class: Radiopharmaceutical, Antineoplastic

Uses For Metastron

Strontium chloride Sr 89 is a radiopharmaceutical. Radiopharmaceuticals are radioactive agents that may be used to diagnose some diseases by studying the function of the body's organs or to treat certain diseases.

Strontium chloride Sr 89 is used to help relieve the bone pain that may occur with certain kinds of cancer. The radioactive strontium is taken up in the bone cancer area and gives off radiation that helps provide relief of pain.

Strontium chloride Sr 89 is to be given only by or under the direct supervision of a doctor with specialized training in nuclear medicine or radiation oncology.

Before Using Metastron

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on this medicine have been done only in adult patients, and there is no specific information about its use in children.

Geriatric

Strontium chloride Sr 89 has been used in older people and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of strontium chloride Sr 89. Make sure you tell your doctor if you have any other medical problems.

Proper Use of Metastron

Your doctor may have special instructions for you to follow to get ready for your treatment. If you do not understand them or if you have not received such instructions, check with your doctor in advance.

If you have a problem controlling your bladder, tell your doctor before receiving strontium chloride Sr 89. Special precautions will need to be taken to prevent contamination of clothing, bed linen, and the environment.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Precautions While Using Metastron

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects. You may need to have blood tests done regularly.

Follow these guidelines for 1 week after receiving strontium chloride Sr 89, to help reduce the chance of contaminating other persons or the environment:

• Use a normal toilet, if available, instead of a urinal.


• Strontium chloride Sr 89 is passed in the urine and feces. To prevent contamination of your home environment, flush the toilet twice after using.


• Wipe any spilled urine with a tissue and flush it away.


• Wash your hands after using or cleaning the toilet .


• Wash your clothes and bed linens immediately if they become soiled with your urine or blood. Wash them separately from other clothes.


• If you cut yourself, wash away any spilled blood .

Strontium chloride Sr 89 can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If your blood count becomes abnormally low, there are certain precautions you can take, to reduce the risk of infection or bleeding, such as:

• With abnormally low white blood cell counts:
  
  • If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
  
  
  • Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
  
  
  • Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
  
  


• With abnormally low platelet blood counts:
  
  • Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
  
  
  • Avoid contact sports or other situations where bruising or injury could occur.
  
  

Metastron Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. When strontium chloride Sr 89 is used at recommended doses, side effects usually are rare. However, blood problems, such as a decrease in the number of white blood cells or platelets, may occur in some patients.

Check with your doctor immediately if any of the following side effects occur:

Rare

• Black, tarry stools


• blood in urine or stools


• cough or hoarseness


• fever or chills


• lower back or side pain


• painful or difficult urination


• pinpoint red spots on skin


• unusual bleeding or bruising

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Flushing


• increase in bone pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Metastron side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Metastron resources

• Metastron Side Effects (in more detail)
• Metastron Drug Interactions
• Metastron Support Group
• 0 Reviews · Be the first to review/rate this drug

• Metastron Prescribing Information (FDA)


• Strontium-89 Chloride Professional Patient Advice (Wolters Kluwer)

ME-Gastroview

Dosage Form: rectal and oral solution
August 2009


MD-Gastroview®


[ DIATRIZOATE MEGLUMINE AND

DIATRIZOATE SODIUM SOLUTION U.S.P. ]


Mallinckrodt Inc.


Rx Only

DESCRIPTION

MD-GASTROVIEW (Diatrizoate Meglumine and Diatrizoate Sodium Solution) is a palatable lemon-vanilla flavored water-soluble iodinated radiopaque contrast medium for oral or rectal administration only. Each mL contains 660 mg diatrizoate meglumine and 100 mg diatrizoate sodium; pH has been adjusted to 6.0 to 7.6 with sodium hydroxide. Each mL contains approximately 4.8 mg (0.21 mEq) sodium and 367 mg organically bound iodine. MD-GASTROVIEW does not contain the wetting agent polysorbate 80.

The inactive ingredients are: Edetate Disodium Dihydrate, Lemon-Vanilla Flavor, Sodium Citrate, Sodium Hydroxide, Sodium Saccharin, Water for Injection. Air in the container is displaced with nitrogen.

Diatrizoate meglumine is designated chemically as 1-deoxy-1-(methylamino)-D-glucitol 3,5-diacetamido-2,4,6-triiodobenzoate (salt); diatrizoate sodium is monosodium 3,5-diacetamido-2,4,6-triiodobenzoate. The two salts have the following structural formulae:

CLINICAL PHARMACOLOGY

The most important characteristic of contrast media is the iodine content. The relatively high atomic weight of iodine contributes sufficient radiodensity for radiographic contrast with surrounding tissues.

Diagnostic enteral radiopaque agents have few known pharmacological effects. Diatrizoate meglumine and diatrizoate sodium exert a mild laxative effect attributable to their high osmolarity.

Diatrizoate meglumine and diatrizoate sodium are sparingly absorbed from the intact gastrointestinal tract, and therefore permit gastrointestinal opacification and delineation after oral or rectal administration. Oral administration is used for radiographic evaluation of the esophagus, stomach and proximal small intestine. Rectal administration is used for examination of the colon; however, visualization of the distal small bowel is generally unsatisfactory, since the hypertonicity of the medium causes intraluminal diffusion of water with subsequent dilution of the medium. Enough absorption from the gastrointestinal tract to permit incidental visualization of the urinary tract has been reported; this should also be considered when thyroid testing is being contemplated, since iodine-mediated thyrotropic effects may occur (see PRECAUTIONS).

INDICATIONS AND USAGE

MD-GASTROVIEW (Diatrizoate Meglumine and Diatrizoate Sodium Solution) is indicated for radiographic examination of segments of the gastrointestinal tract (esophagus, stomach, proximal small intestine, and colon). The preparation is particularly indicated when a more viscous agent such as barium sulfate, which is not water-soluble, is not feasible or is potentially dangerous.

MD-GASTROVIEW may also be used as an adjunct to contrast enhancement in computed tomography of the torso (body imaging); the preparation is indicated, in conjunction with intravenous administration of a radiopaque contrast agent, when unenhanced imaging may not provide sufficient definition in distinguishing normal loops of bowel from adjacent organs or areas of suspected pathology.

CONTRAINDICATIONS

Do not administer to patients with a known hypersensitivity to MD-GASTROVIEW or any of its components.

WARNINGS

Dehydration: Administration of hypertonic MD-GASTROVIEW solutions may lead to hypovolemia and hypotension due to fluid loss from the intestine. A 1 in 4.6 (1:4.6) dilution of MD-GASTROVIEW yields an approximately isotonic 16.5 percent diatrizoate salts solution; less dilute solutions are hypertonic and may lead to intraluminal movement of fluid with resulting hypovolemia. In young or debilitated children and in elderly cachectic persons, the loss of plasma fluid may be sufficient to cause a shock-like state. If MD-GASTROVIEW is used in infants and children (under 10 kg) or in dehydrated or debilitated patients, the solution must be prepared using the specific dilutions described in DOSAGE AND ADMINISTRATION. In debilitated patients and in patients with electrolyte imbalances, postprocedural monitoring of hydration, serum osmolarity, electrolytes and clinical status is essential. In pediatric or severely debilitated patients, the maintenance of an open intravenous fluid line for rehydration may be advisable should hypotension or shock supervene. Electrolyte disturbances must be corrected prior to the administration of any hypertonic MD-GASTROVIEW solutions.

Aspiration: Aspiration of MD-GASTROVIEW into the trachea and airways may result in serious pulmonary complications including, pulmonary edema, pneumonitis or death. Bronchial entry of any orally administered contrast medium causes a copious osmotic effusion. Therefore, avoid use of MD-GASTROVIEW in patients with esophagotracheal fistula and minimize risks for pulmonary aspiration in all patients. If MD-GASTROVIEW is given by nasogastric tube, the position of the tube in the stomach must be verified before administration.

Anaphylactic Reactions: Anaphylactic reactions, including fatalities, have been reported with the use of MD-GASTROVIEW. Patients at increased risk include those with a history of a previous reaction to a contrast medium, patients with a known sensitivity to iodine, and patients with a known clinical hypersensitivity (bronchial asthma, hay fever, and food allergies). Medical personnel trained in the treatment of anaphylactic reactions and the necessary drugs and medical equipment should always be readily available when MD-GASTROVIEW is used.

PRECAUTIONS

General

Diagnostic procedures which involve the use of radiopaque contrast agents should be carried out under the direction of personnel with the prerequisite training and with a thorough knowledge of the particular procedure to be performed. Appropriate facilities should be available for coping with any complication of administration, as well as for treatment of reaction to the contrast medium (see ADVERSE REACTIONS, and PRECAUTIONS, Information for the Patient).

Rectal administration of undiluted MD-GASTROVIEW in any patient, particularly with large doses and/or in those with overdistention, has been reported to be associated with mucosal irritation.

Cases of hyperthyroidism have been reported with the use of oral contrast media. Some of these patients reportedly had multinodular goiters which may have been responsible for the increased hormone synthesis in response to excess iodine. Administration of an intravascular iodinated radiopaque diagnostic agent to a hyperthyroid patient precipitated thyroid storm; a similar situation could follow administration of oral preparations of iodides. Therefore, caution should be exercised when administering enteral gastrointestinal radiopaque agents to hyperthyroid and euthyroid goiterous patients.

Consideration should be given to the potential for precipitation of water-soluble contrast agents under conditions that may promote hyperacidity (i.e., fasting, emotional upset, or stress). Harmful effects directly attributable to precipitate formation have not been reported. However, the possibility of interpreting the precipitate radiologically as an anatomical abnormality (i.e., ulceration of the stomach or small intestine) or injury, should be kept in mind.

Information for the Patient

Patients should receive the following information and instructions:

1. This drug has been prescribed to perform an X-ray of the gastrointestinal tract.


2. Inform the physician if pregnant or if allergic to iodine, any foods, or X-ray materials.


3. The iodine in diatrizoate salts may interfere with some thyroid tests if these are needed in the future. Inform the attending physician at that time about this gastrointestinal study.


4. This drug may cause abdominal cramping, nausea, vomiting, diarrhea, skin rashes, itching, heartburn, dizziness, or headache in some patients, but most reactions are mild and pass quickly.

Drug/Laboratory Test Interactions

Thyroid Function Tests

The results of protein bound iodine (PBI) and radioactive iodine uptake studies, which depend on iodine estimations, will not accurately reflect thyroid function for six months, and possibly as long as one year, following the administration of diagnostic enteral radiopaque media.

Thyroid function tests, if indicated, generally should be performed prior to the administration of any iodinated agent. However, thyroid function can be evaluated after use of these agents by using T3 resin uptake and total or free thyroxine (T4) assays, which are not dependent on iodine estimations.

Pancreatic Tests

Small quantities of contrast medium in the intestinal tract may cause false low trypsin values when determined spectrophotometrically. Therefore, duodenal instillation should not precede pancreatic function tests involving spectrophotometric trypsin assays.

Any test which might be affected by contrast media should be performed prior to administration of the contrast medium.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential, or possible impairment of fertility in males or females.

Pregnancy Category B

When administered intravenously, diatrizoate salts cross the placenta and are evenly distributed in fetal tissues.

No teratogenic effects attributable to diatrizoate meglumine or diatrizoate sodium have been observed in teratology studies performed in animals. There are, however, no adequate and well-controlled studies in pregnant women. Because small amounts of these agents may be absorbed, and animal teratology studies are not always predictive of human response, these agents should be used during pregnancy only when clearly needed.

Procedures including radiation involve a certain risk related to the exposure of the fetus.

Nursing Mothers

Diatrizoate meglumine is excreted in breast milk following intravascular administration.

Because small amounts of enteral gastrointestinal radiopaque agents may be absorbed following oral or rectal administration, caution should be exercised when they are administered to a nursing woman.

Pediatric Use

See WARNINGS, and PRECAUTIONS, General.

Local injury to the colonic mucosa, particularly in the presence of underlying disease which interferes with intestinal viability, has been reported in cases where recommended doses and dilutions (see DOSAGE AND ADMINISTRATION) were not used.

Adverse Reactions

Most adverse reactions to enteral diagnostic radiopaque agents are mild and transitory. Nausea, vomiting and/or diarrhea, urticaria with erythema, hypoxia, acute dyspnea, tachyarrhythmia, and anaphylaxis have occurred following ingestion of the contrast medium, particularly when high concentrations or large volumes of solution are administered. Severe changes in serum osmolarity and electrolyte concentrations may produce shock-like states (see WARNINGS). It should be kept in mind that serious or anaphylactoid reactions that may occur with intravascular administration of radiopaque contrast agents are theoretically possible following administration by other routes.

OVERDOSAGE

See WARNINGS regarding potential hypovolemia, hypotension, or shock. The maintenance of an open intravenous fluid line for rehydration may be advisable. See DOSAGE AND ADMINISTRATION for appropriate doses and dilutions. Treatment of an overdose should be directed toward the support of all vital functions, and prompt institution of symptomatic therapy.

DOSAGE AND ADMINISTRATION

General

This medium is not to be used for the preparation of solutions for parenteral administration. Oral or rectal use only.

The routine preparatory measures employed for barium studies are also appropriate for this agent.

For pediatric and severely cachectic patients, the maintenance of an intravenous fluid line may be advisable.

Radiographic Examination of Segments of the Gastrointestinal Tract

Oral Administration: Adult oral dosage may range from 30 to 90 mL (11 to 33 g iodine), depending on the nature of the examination and the size of the patient. For infants and children less than 5 years of age, 30 mL (11 g iodine) are usually adequate; for children 5 to 10 years of age, the suggested dose is 60 mL (22 g iodine). These pediatric doses may be diluted 1:1, if desired, with water, carbonated beverage, milk, or mineral oil. When used in infants, the solution may be given in a nursing bottle. Pediatric doses may also be used in dehydrated and/or debilitated adult patients. A 1:1 dilution is also recommended when the contrast medium is used in elderly cachectic individuals.

For very young (under 10 kg) and debilitated children the dose should be diluted: 1 part MD-GASTROVIEW (Diatrizoate Meglumine and Diatrizoate Sodium Solution) in 3 parts water is recommended.

For Enemas or Enterostomy Instillations: MD-GASTROVIEW should be diluted when it is used for enemas and enterostomy instillations.

When used as an enema, the suggested dilution for adults is 240 mL (88 g iodine) in 1,000 mL of tap water. For children under 5 years of age, a 1:5 dilution in tap water is suggested; for children over 5 years of age, 90 mL (33 g iodine) in 500 mL of tap water is a suitable dilution.

Tomography (Body Imaging)

A usual adult dose is 240 mL of a dilute MD-GASTROVIEW solution prepared by diluting 25 mL (9.17 g iodine) to one liter with tap water. Less dilute solutions [up to 77 mL (28.26 g iodine) diluted to one liter with tap water] may be used when indicated. The dose is administered orally about 15 to 30 minutes prior to imaging in order to permit the contrast medium to reach the pelvic loops.

HOW SUPPLIED

Available as an aqueous lemon-vanilla flavored solution in bottles of 30 mL in packages of 25 (NDC 0019-4816-04), in bottles of 120 mL in packages of 12 (NDC 0019-4816-05), and in bottles of 240 mL in packages of 12 (NDC 0019-4816-06).

Storage

Protect from light. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]; Avoid excessive heat. If precipitation or solidification has occurred due to storage in the cold, the bottle should be brought to room temperature. Shake intermittently to redissolve any solids.

As with all contrast media, containers should be inspected prior to use to ensure that breakage or other damage has not occurred during shipping and handling. All containers should be inspected for closure integrity. Damaged containers should not be used.

MD-Gastroview is a registered trademark of Mallinckrodt Inc.

tyco / Healthcare

Mallinckrodt

Mallinckrodt Inc.

St. Louis, MO 63042 USA

www.Mallinckrodt.com

MKR 48160809

Rev 08/2009

Printed in U.S.A.

PACKAGE LABEL - PRINCIPAL DISPLAY PANEL - Case Label

MD-Gastroview®


DIATRIZOATE MEGLUMINE AND DIATRIZOATE SODIUM SOLUTION U.S.P.


37% Organically Bound Iodine For Gastrointestinal Radiography


Not For Parenteral Use


Rx Only


11040809

MD-GASTROVIEW   diatrizoate meglumine and diatrizoate sodium  solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0019-4816 Route of Administration RECTAL, ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DIATRIZOATE MEGLUMINE (DIATRIZOIC ACID) DIATRIZOATE MEGLUMINE 600 mg  in 1 mL DIATRIZOATE SODIUM (DIATRIZOIC ACID) DIATRIZOATE SODIUM 100 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength EDETATE DISODIUM   GLYCINE   SODIUM CITRATE   SODIUM HYDROXIDE   SACCHARIN SODIUM   WATER

Product Characteristics Color      Score      Shape Size Flavor LEMON, VANILLA Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0019-4816-04 25  In 1 BOX contains a BOTTLE, GLASS 1 30 mL In 1 BOTTLE, GLASS This package is contained within the BOX (0019-4816-04)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA087388	08/31/2009

Labeler - Mallinckrodt Inc. (047021092)

Establishment
Name	Address	ID/FEI	Operations
Mallinckrodt Inc.		109024984	analysis, manufacture

Establishment
Name	Address	ID/FEI	Operations
JUSTESA IMAGEN SA		477020325	api manufacture

Revised: 08/2011Mallinckrodt Inc.

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