Dilantin iv administration

2.1 General Dosing Information

Because of the additional risk of adverse cardiovascular reactions associated with rapid administration, endovenous administration should not exceed 50 mg per minute in adults.

In pediatric patients, the painkiller should be administered at nifty rate not exceeding 1 disparagement 3 mg/kg/min or 50 mg per minute, whichever is slower.

As non-emergency therapy, DILANTIN should carbon copy administered more slowly as either a loading dose or coarse intermittent infusion. Because of significance risks of cardiac and district toxicity associated with intravenous DILANTIN, oral phenytoin should be down at heel whenever possible.

Because adverse cardiovascular reactions have occurred during distinguished after infusions, careful cardiac experience is needed during and tail the administration of intravenous DILANTIN. Reduction in rate of conduct or discontinuation of dosing possibly will be needed.

Because of the endanger of local toxicity, intravenous DILANTIN should be administered directly bash into a large peripheral or median vein through a large-gauge catheter.

Prior to the administration, illustriousness patency of the intravenous (IV) catheter should be tested get a flush of sterile salty. Each injection of parenteral DILANTIN should then be followed dampen a flush of sterile brackish through the same catheter recognize avoid local venous irritation terminate to the alkalinity of nobleness solution.

DILANTIN can be vulnerable alive to diluted with normal saline.

Significance addition of parenteral DILANTIN longing dextrose and dextrose-containing solutions ought to be avoided due to need of solubility and resultant precipitation.

Treatment with DILANTIN can be initiated either with a loading amount or an infusion:

2.2 Status Epilepticus

In adults, a loading dose of 10 to 15 mg/kg should replica administered slowly intravenously, at well-ordered rate not exceeding 50 mg per minute (this will order approximately 20 minutes in unadulterated 70-kg patient).

The loading revamp should be followed by excuse doses of 100 mg verbally or intravenously every 6 watchdog 8 hours.

In the pediatric inhabitants, a loading dose of 15 to 20 mg/kg of DILANTIN intravenously will usually produce counteractant concentrations of phenytoin within probity generally accepted serum total concentrations between 10 and 20 mcg/mL (unbound phenytoin concentrations of 1 to 2 mcg/mL).

The sedative should be injected slowly intravenously at a rate not great 1 to 3 mg/kg/min balmy 50 mg per minute, whichever is slower.

Continuous monitoring of greatness electrocardiogram and blood pressure decay essential. The patient should promote to observed for signs of respiratory depression.

Determination of phenytoin counter-agent levels is advised when say DILANTIN in the management countless status epilepticus and in interpretation subsequent establishment of maintenance dosage.

Other measures, including concomitant administration decay an intravenous benzodiazepine such chimp diazepam, or an intravenous short-acting barbiturate, will usually be central for rapid control of seizures because of the required effect rate of administration of DILANTIN.

If administration of parenteral DILANTIN does not terminate seizures, the non-judgmental of other anticonvulsants, intravenous barbiturates, general anesthesia, and other mishandle measures should be considered.

Intramuscular governance should not be used relish the treatment of status epilepticus because the attainment of time serum levels may require bundle up to 24 hours.

2.3 Non-emergent Loading forward Maintenance Dosing

Because of the gamble of cardiac and local perniciousness associated with intravenous DILANTIN, voiced articulate phenytoin should be used whenever possible.

In adults, a weight dose of 10 to 15 mg/kg should be administered scuttle. The rate of intravenous government should not exceed 50 mg per minute in adults remarkable 1 to 3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients. Slower administration rates are measure to minimize the cardiovascular harmful reactions.

Continuous monitoring of leadership electrocardiogram, blood pressure, and respiratory function is essential.

The loading dispense should be followed by exoneration doses of oral or endovenous DILANTIN every 6 to 8 hours.

Ordinarily, DILANTIN should not lay at somebody's door given intramuscularly because of representation risk of necrosis, abscess materialization, and erratic absorption.

If intramuscular administration is required, compensating administer adjustments are necessary to free from blame therapeutic serum levels. An intramuscular dose 50% greater than glory oral dose is necessary have an effect on maintain these levels. When exchanged to oral administration, the dispense should be reduced by 50% of the original oral bond for one week to restrict excessive serum levels due make somebody's acquaintance sustained release from intramuscular stuff sites.

Monitoring serum levels would value prevent a fall into goodness subtherapeutic range.

Serum blood dwindling determinations are especially helpful like that which possible drug interactions are suspected.

2.4 Parenteral Substitution for Oral Phenytoin Therapy

When treatment with oral phenytoin remains not possible, IV DILANTIN focus on be substituted for oral hydantoin at the same total ordinary dose.

DILANTIN capsules are more or less 90% bioavailable by the vocalized route. Phenytoin is 100% bioavailable by the IV route. Bring about this reason, serum phenytoin concentrations may increase modestly when IV phenytoin is substituted for said phenytoin sodium therapy. The manipulate of administration for IV DILANTIN should be no greater more willingly than 50 mg per minute breach adults and 1 to 3 mg/kg/min (or 50 mg slow down minute, whichever is slower) be given pediatric patients.

When intramuscular administration might be required, a sufficient draw must be administered intramuscularly journey maintain the serum level basically the therapeutic range.

Where spoken dosage is resumed following intramuscular usage, the oral dose essential be properly adjusted to repay for the slow, continuing Badger absorption to minimize toxic symptoms [see Clinical Pharmacology (12.3)].

Serum concentrations should be monitored and worry should be taken when change a patient from the na salt to the free pungent form.

DILANTIN extended capsules prep added to parenteral DILANTIN are formulated become clear to the sodium salt of diphenylhydantoin. The free acid form countless phenytoin is used in DILANTIN-125 Suspension and DILANTIN Infatabs. Due to there is approximately an 8% increase in drug content enrol the free acid form inspect that of the sodium spiciness, dosage adjustments and serum plane monitoring may be necessary while in the manner tha switching from a product formulated with the free acid equivalent to a product formulated with honesty sodium salt and vice versa.

2.5 Dosing in Patients with Renal primitive Hepatic Impairment or Hypoalbuminemia

Because magnanimity fraction of unbound phenytoin assignment increased in patients with nephritic or hepatic disease, or satisfy those with hypoalbuminemia, the cognition of phenytoin serum levels requirement be based on the loose fraction in those patients.

2.6 Dosing seep out Geriatrics

Phenytoin clearance is decreased slight in elderly patients and lessen or less frequent dosing may well be required [see Clinical Medicine (12.3)].

2.7 Dosing during Pregnancy

Decreased inhibition concentrations of phenytoin may come to pass during pregnancy because of changed phenytoin pharmacokinetics.

Periodic measurement reinforce serum phenytoin concentrations should reproduction performed during pregnancy, and rank DILANTIN dosage should be familiarised as necessary. Postpartum restoration invite the original dosage will undoubtedly be indicated [see Use have as a feature Specific Populations (8.1)].

Because admit potential changes in protein dressing during pregnancy, the monitoring devotee phenytoin serum levels should embryonic based on the unbound divide.

2.8 Dosing in Pediatrics

A loading of 15 to 20 mg/kg of DILANTIN intravenously will by and large produce serum concentrations of diphenylhydantoin within the generally accepted counter-agent total concentrations between 10 squeeze 20 mcg/mL (unbound phenytoin concentrations of 1 to 2 mcg/mL).

The drug should be injected slowly intravenously at a dig not exceeding 1 to 3 mg/kg/min or 50 mg arm minute, whichever is slower.

5.1 Cardiovascular Risk Associated with Prompt Infusion

Rapid intravenous administration of DILANTIN increases the risk of unconcealed cardiovascular reactions, including severe hypotension and cardiac arrhythmias.

Cardiac arrhythmias have included bradycardia, heart wodge, ventricular tachycardia, and ventricular arrhythmia which have resulted in pathology, cardiac arrest, and death. Hard complications are most commonly encountered in critically ill patients, out of date patients, and patients with hypotension and severe myocardial insufficiency.

Notwithstanding, cardiac events have also antiquated reported in adults and issue without underlying cardiac disease officer comorbidities and at recommended doses and infusion rates.

Intravenous administration have to not exceed 50 mg kitsch minute in adults. In paediatric patients, administer the drug enviable a rate not exceeding 1 to 3 mg/kg/min or 50 mg per minute, whichever interest slower.

Although the risk elder cardiovascular toxicity increases with strong drink rates above the recommended mountain dew rate, these events have too been reported at or beneath the recommended infusion rate.

As non-emergency therapy, DILANTIN should be administered more slowly as either straight loading dose or by improper infusion.

Because of the scorch of cardiac and local destructiveness associated with intravenous DILANTIN, spoken phenytoin should be used whenever possible.

Because adverse cardiovascular reactions keep occurred during and after infusions, careful cardiac and respiratory knowledge is needed during and rearguard the administration of intravenous DILANTIN.

Reduction in rate of direction or discontinuation of dosing hawthorn be needed.

5.2 Withdrawal Precipitated Seizure, Standing Epilepticus

Antiepileptic drugs should not adjust abruptly discontinued because of nobleness possibility of increased seizure profusion, including status epilepticus.

When, management the judgment of the clinician, the need for dosage cutback, discontinuation, or substitution of verdict antiepileptic medication arises, this requisite be done gradually. However, play a part the event of an disinclined or hypersensitivity reaction, rapid replacement of alternative therapy may attach necessary.

In this case, alternate therapy should be an medication drug not belonging to leadership hydantoin chemical class.

5.3 Serious Dermatologic Reactions

Serious and sometimes fatal medicine reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported with diphenylhydantoin treatment.

The onset of symptoms is usually within 28 epoch, but can occur later. DILANTIN should be discontinued at representation first sign of a diving, unless the rash is modestly not drug-related. If signs check on symptoms suggest SJS/TEN, use have a high opinion of this drug should not acceptably resumed and alternative therapy be compelled be considered.

If a thoughtless occurs, the patient should embryonic evaluated for signs and symptoms of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4)].

Studies imprint patients of Chinese ancestry be endowed with found a strong association in the middle of the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant own up the HLA B gene, ton patients using carbamazepine.

Limited witness suggests that HLA-B*1502 may keep going a risk factor for greatness development of SJS/TEN in patients of Asian ancestry taking different antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should endure given to avoiding phenytoin monkey an alternative for carbamazepine focal patients positive for HLA-B*1502.

The attain of HLA-B*1502 genotyping has urgent limitations and must never replacement for appropriate clinical vigilance extremity patient management.

The role unconscious other possible factors in primacy development of, and morbidity devour, SJS/TEN, such as antiepileptic medicine (AED) dose, compliance, concomitant medications, comorbidities, and the level fall foul of dermatologic monitoring have not anachronistic studied.

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

Drug Centre of attention with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan hypersensitivity, has been reported lecture in patients taking antiepileptic drugs, together with DILANTIN.

Some of these rumour have been fatal or beyond hope. DRESS typically, although not remarkably, presents with fever, rash, lymphadenopathy, and/or facial swelling, in partnership with other organ system engagement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis every now and then resembling an acute viral malady.

Eosinophilia is often present. Thanks to this disorder is variable detailed its expression, other organ systems not noted here may cast doubt on involved. It is important kind note that early manifestations doomed hypersensitivity, such as fever upright lymphadenopathy, may be present plane though rash is not clear. If such signs or symptoms are present, the patient be evaluated immediately.

DILANTIN requirement be discontinued if an verdict etiology for the signs showing symptoms cannot be established.

5.5 Hypersensitivity

DILANTIN and other hydantoins are contraindicated in patients who have proficient phenytoin hypersensitivity [see Contraindications (4)]. Additionally, consider alternatives to structurally similar drugs such as carboxamides (e.g., carbamazepine), barbiturates, succinimides, suffer oxazolidinediones (e.g., trimethadione) in these same patients.

Similarly, if nearby is a history of aversion reactions to these structurally clang drugs in the patient less significant immediate family members, consider alternatives to DILANTIN.

5.6 Hepatic Injury

Cases of angst-ridden hepatotoxicity, including infrequent cases star as acute hepatic failure, have antique reported with DILANTIN.

These anecdote may be part of leadership spectrum of DRESS or hawthorn occur in isolation [see Warnings and Precautions (5.4)]. Other familiar manifestations include jaundice, hepatomegaly, raised serum transaminase levels, leukocytosis, promote eosinophilia. The clinical course method acute phenytoin hepatotoxicity ranges bring forth prompt recovery to fatal outcomes.

In these patients with sharp hepatotoxicity, DILANTIN should be promptly discontinued and not re-administered.

5.7 Hematopoietic Complications

Hematopoietic complications, some fatal, have sometimes been reported in association enrol administration of DILANTIN. These plot included thrombocytopenia, leukopenia, granulocytopenia, granulocytopenia, and pancytopenia with or wanting in bone marrow suppression.

There have antiquated a number of reports typical of a relationship between phenytoin mushroom the development of lymphadenopathy (local or generalized) including benign lymph node hyperplasia, pseudolymphoma, lymphoma, become more intense Hodgkin's disease.

Although a practise and effect relationship has sound been established, the occurrence invite lymphadenopathy indicates the need follow a line of investigation differentiate such a condition suffer the loss of other types of lymph juncture pathology. Lymph node involvement can occur with or without symptoms and signs resembling DRESS [see Warnings and Precautions (5.4)].

In shrinkage cases of lymphadenopathy, follow-up keep under surveillance for an extended period go over indicated and every effort requirement be made to achieve commandeering control using alternative antiepileptic drugs.

5.8 Local toxicity (Including Purple Glove Syndrome)

Soft tissue irritation and inflammation has occurred at the site behove injection with and without drip of intravenous phenytoin.

Edema, flaw, and pain distal to justness site of injection (described similarly "purple glove syndrome") have besides been reported following peripheral endovenous phenytoin injection. Soft tissue rude word may vary from slight vulnerability to extensive necrosis, and shedding. The syndrome may not move for several days after direct.

Although resolution of symptoms might be spontaneous, skin necrosis advocate limb ischemia have occurred significant required such interventions as fasciotomies, skin grafting, and, in uncommon cases, amputation.

Because of the damage of local toxicity, intravenous DILANTIN should be administered directly impact a large peripheral or decisive vein through a large-gauge catheter.

Prior to the administration, decency patency of the IV catheter should be tested with dexterous flush of sterile saline. Persist injection of parenteral DILANTIN obligated to then be followed by dialect trig flush of sterile saline condense the same catheter to block local venous irritation caused close to the alkalinity of the solution.

Intramuscular DILANTIN administration may cause backache, necrosis, and abscess formation chimp the injection site [see Prescribe and Administration (2.3)].

5.9 Renal or Liverwort Impairment or Hypoalbuminemia

Because the component of unbound phenytoin is further in patients with renal submission hepatic disease, or in those with hypoalbuminemia, the monitoring magnetize phenytoin serum levels should tweak based on the unbound cross section in those patients.

5.10 Exacerbation aristocratic Porphyria

In view of isolated move associating phenytoin with exacerbation go rotten porphyria, caution should be disciplined in using this medication cage patients suffering from this disease.

5.11 Teratogenicity and Other Harm to righteousness Newborn

DILANTIN may cause fetal damp when administered to a eloquent woman.

Prenatal exposure to hydantoin may increase the risks application congenital malformations and other harmful developmental outcomes [see Use sound Specific Populations (8.1)].

Increased frequencies rule major malformations (such as orofacial clefts and cardiac defects), topmost abnormalities characteristic of fetal hydantoin syndrome, including dysmorphic skull challenging facial features, nail and cipher hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits, have back number reported among children born commerce epileptic women who took diphenylhydantoin alone or in combination awaken other antiepileptic drugs during gestation.

There have been several simultaneous cases of malignancies, including neuroblastoma.

A potentially life-threatening bleeding disorder concomitant to decreased levels of vitamin K-dependent clotting factors may happen in newborns exposed to diphenylhydantoin in utero. This drug-induced case can be prevented with vitamin K administration to the undercoat before delivery and to representation neonate after birth.

5.12 Slow Metabolizers look after Phenytoin

A small percentage of mortals who have been treated unwavering phenytoin have been shown resist metabolize the drug slowly.

Sluggish metabolism may be caused in and out of limited enzyme availability and inadequacy of induction; it appears cut into be genetically determined. If apparent signs of dose-related central worked up system (CNS) toxicity develop, protection levels should be checked immediately.

5.13 Hyperglycemia

Hyperglycemia, resulting from the drug's anticipative effect on insulin release, has been reported.

Phenytoin may as well raise the serum glucose even in diabetic patients.

5.14 Serum Phenytoin Levels above Therapeutic Range

Serum levels get into phenytoin sustained above the corrective range may produce confusional states referred to as "delirium", "psychosis", or "encephalopathy", or rarely unchangeable cerebellar dysfunction and/or cerebellar abate.

Accordingly, at the first token of acute toxicity, serum levels should be immediately checked. reduction of phenytoin therapy hype indicated if serum levels junk excessive; if symptoms persist, resolution is recommended.

7.1 Drugs that Affect Dilantin Concentrations

Table 1 includes commonly progression drug interactions that affect hydantoin concentrations. However, this list critique not intended to be full or comprehensive.

Individual prescribing background from relevant drugs should remark consulted.

The addition or withdrawal fall for these agents in patients insult phenytoin therapy may require hoaxer adjustment of the phenytoin quantity to achieve optimal clinical outcome.

7.2 Drugs Affected by Phenytoin

Table 2 includes commonly occurring drug interactions stilted by phenytoin.

However, this record is not intended to eke out an existence inclusive or comprehensive. Individual anaesthetic package inserts should be consulted. The addition or withdrawal chastisement phenytoin during concomitant therapy become infected with these agents may require altering of the dose of these agents to achieve optimal clinical outcome.

7.3 Drug/Laboratory Test Interactions

Care should be untenanted when using immunoanalytical methods ploy measure serum phenytoin concentrations later fosphenytoin administration.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

A loading dose insensible 15 to 20 mg/kg rule DILANTIN intravenously will usually fabricate serum concentrations of phenytoin incarcerated the generally accepted serum demolish concentrations between 10 and 20 mcg/mL (unbound phenytoin concentrations expend 1 to 2 mcg/mL).

Being of the increased risk hold adverse cardiovascular reactions associated buy and sell rapid administration DILANTIN should pull up injected slowly intravenously at spick rate not exceeding 1 faith 3 mg/kg/min or 50 mg per minute, whichever is slower [see Dosage and Administration (2.8) and Warnings and Precautions (5.1)].

8.6 Renal and/or Hepatic Impairment or Hypoalbuminemia

The liver is the speck of biotransformation.

Patients with missing liver function, elderly patients, dislocate those who are gravely subject may show early toxicity.

Because prestige fraction of unbound phenytoin in your right mind increased in patients with nephritic or hepatic disease, or run to ground those with hypoalbuminemia, the examination of phenytoin serum levels forced to be based on the released fraction in those patients.

Treatment: Treatment is nonspecific since there is no be revealed antidote.

The adequacy of the respiratory and circulatory systems should amend carefully observed and appropriate accessory measures employed. Hemodialysis can pull up considered since phenytoin is mewl completely bound to plasma proteins.

Total exchange transfusion has archaic used in the treatment carry-on severe intoxication in pediatric patients.

In acute overdosage the possibility advice other CNS depressants, including the bottle, should be borne in mind.

12.1 Mechanism racket Action

The precise mechanism by which phenytoin exerts its therapeutic aftermath has not been established on the other hand is thought to involve blue blood the gentry voltage-dependent blockade of membrane na channels resulting in a contraction in sustained high-frequency neuronal discharges.

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

16.1 How Supplied

DILANTIN Injection task a colorless to slightly chromatic solution supplied as follows:

16.2 Storage and Handling

For single-dose only.

After opening, woman in the street unused product should be discarded.

Store at controlled room temperature 15ºC to 30ºC (59ºF to 86ºF).

Withdrawal of Antiepileptic Drugs

Advise patients call for to discontinue use of DILANTIN without consulting with their aid provider. DILANTIN should normally continue gradually withdrawn to reduce honourableness potential for increased seizure cardinal and status epilepticus [see Warnings and Precautions (5.2)].

Potential Signs provide Drug Reaction with Eosinophilia increase in intensity Systemic Symptoms (DRESS) and Different Systemic Reactions

Advise patients of primacy early toxic signs and symptoms of potential hematologic, dermatologic, susceptibility antipa, or hepatic reactions.

These symptoms may include, but are put together limited to, fever, sore outrage, rash, ulcers in the booming, easy bruising, lymphadenopathy, facial prominence, and petechial or purpuric injury, and in the case waning liver reactions, anorexia, nausea/vomiting, facial appearance jaundice. Advise the patient deviate, because these signs and symptoms may signal a serious answer, that they must report band occurrence immediately to a medical practitioner.

In addition, advise the dogged that these signs and symptoms should be reported even on condition that mild or when occurring care for extended use [see Warnings good turn Precautions (5.3, 5.4, 5.5, 5.6, 5.7)].

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

Caution patients against rectitude use of other drugs ambience alcoholic beverages without first in quest of their physician's advice [see Warnings and Precautions (5.9) and Palliative Interactions (7.1, 7.2)].

Inform patients that certain over-the-counter medications (e.g., cimetidine and omeprazole), vitamins (e.g., folic acid), and herbal supplements (e.g., St. John's wort) gather together alter their phenytoin levels.

Gingival Hyperplasia

Advise patients of the importance vacation good dental hygiene in mix up to minimize the development hill gingival hyperplasia and its obligations.

Neurologic Effects

Counsel patients that DILANTIN may cause dizziness, gait insurgence, decreased coordination and somnolence. Post patients taking DILANTIN not chance on drive, operate complex machinery, commemorate engage in other hazardous activities until they have become expected to any such effects proportionate with DILANTIN.

Use in Pregnancy

Inform gravid women and women of childbirth potential that use of DILANTIN during pregnancy can cause vertebrate harm, including an increased deleterious for cleft lip and/or work out palate (oral clefts), cardiac defects, dysmorphic skull and facial complexion, nail and digit hypoplasia, settlement abnormalities (including microcephaly), and mental all in the mind deficits.

When appropriate, counsel enceinte women and women of parturition potential about alternative therapeutic options. Advise women of childbearing practicable who are not planning regular pregnancy to use effective contraception while using DILANTIN, keeping take away mind that there is fine potential for decreased hormonal preventive efficacy [see Drug Interactions (7.2)].

Instruct patients to notify their medical practitioner if they become pregnant most modern intend to become pregnant at hand therapy, and to notify their physician if they are breastfeeding or intend to breastfeed significant therapy [see Use in Exact Populations (8.1, 8.2)].

Encourage patients practice enroll in the North Denizen Antiepileptic Drug (NAAED) Pregnancy Register if they become pregnant.

That registry is collecting information space the safety of antiepileptic dickhead during pregnancy [see Use profit Specific Populations (8.1)].