Fosphenytoin (Injection)

Overview

Fosphenytoin is known by its marketing name of Cerebyx in the US as well as Prodilantin in European markets. This drug produces Phenytoin when introduced to the body as a prodrug, which is a drug that is non-active until metabolized. Considered to be much safer than the intravenously administered Phenytoin, Fosphenytoin has been approved for use since 1996.

Fosphenytoin is used only in a professional medical setting such as a hospital or clinic. It is most often prescribed for use in epileptic patients and to prevent and treat neurosurgical related convulsions or seizures.

How does Fosphenytoin work?

After being introduced to the body via injection route, Fosphenytoin changes to an anticonvulsant drug known as Phenytoin on a one to one ratio. Fosphenytoin itself is a prodrug in that it does not have any effect until it changes, which requires interaction with certain enzymes in the body.

Fosphenytoin affects the motor cortex of the brain, which is the area that controls movement, both voluntary and involuntary. Fosphenytoin works to stop the seizure activity from spreading, reducing the chance of the seizure becoming full blown, also known as grand mal.

Fosphenytoin is believed to stop the involuntary energy conduction activity in the brain cells of someone experiencing a seizure. By passing through the neuron cell membranes, Fosphenytoin serves to dampen abnormal energy synapses, normalizing activity and calming the seizure. This drug is intended for the short-term use of five days or less or until the patient can be assigned other drug treatment for long-term care.

Fosphenytoin has been determined to be faster acting than Phenytoin, which has proven to result in better control over seizures. Fosphenytoin is also tolerated well compared to Phenytoin, with a lower risk for heart rhythm and low blood pressure risks. Fosphenytoin additionally does not demonstrate a risk for purple glove syndrome, which is a skin condition sometimes severe enough to require amputation. Purple glove syndrome is associated with IV administration of Phenytoin.

Epilepsy is a brain condition that gives the patient seizures on a semi-regular basis. All brain activity is electrical, consisting of cellular communication back and forth. When a person has a seizure, it is the result of an explosion of electrical activity in the brain cells, which temporarily disrupt normal function.

The type of seizure a person has depends on the part of the brain that is affected by the energy burst. Not all seizures are epileptic in nature and not all seizures are controlled with drugs such as Fosphenytoin and Phenytoin.

Conditions Treated

• Seizures
• Convulsions
• Refractory seizure disorders

Type Of Medicine

• Prodrug
• Anti-epileptic agent
• Central nervous system agent
• Anti-convulsant
• Central nervous system depressant

Side Effects

Fosphenytoin, through its active drug ingredient of Phenytoin, directly affects brain activity at the cellular level, in the motor cortex portion of the brain. It is a very powerful drug and, due to the way it works, may cause adverse health effects that can require urgent medical attention. Notify your physician or medical staff if you exhibit any of the following symptoms:

• Confused demeanor
• Blurry vision
• Fainting, dizziness, or becoming lightheaded when rising
• Hot or warm feeling
• Flushed or red skin on neck and face
• Headaches
• Sweats
• Fatigue
• Muscle weakness
• Bruises that are unexpected
• Anxious demeanor
• Itching, crawling, burning, numb, prickling needles and pins feeling
• Speech rhythm or pattern changes
• Convulsions
• Speaking is difficult
• Drooling
• Mouth is dry
• Rapid or irregular heart rhythm
• Hyperventilating
• Irritable mood
• Skin itches or appears red
• Lack of muscle coordination
• Skin patches that are flat, large in size and a purple or blue color
• Lack of balancing ability
• Jerky, trembling, stiff muscles
• Nervous demeanor
• Difficulty moving, speaking or walking
• Restless mood
• Shaking arms, legs, feet or hands
• Gasping for breath
• Shuffling instead of walking
• Speech is slurred
• Limbs are stiff
• Sleeping is difficult
• Body twists and moves without volition
• Spastic neck, face or back movements
• Trembling, unsteady muscles or other coordination issues
• Vomiting
• Abdominal pain
• Body movement is difficult or stops
• Angry, aggressive demeanor
• Agitated mood
• Stools are tar-like or black in appearance
• Gums bleed
• Sensation of cold
• Discolored skin or blistering, burning skin
• Hives
• Bleeding skin
• Infection or inflammation of the skin
• Itchy, irritated, stinging sensation on the skin
• Sore, red, rash-like skin
• Injection site irritation or swelling
• Skin flakes, becomes dry and crusty or blistered
• Stool or urine has signs of blood
• Nosebleeds
• Fingernails appear blue
• Lips, palms or nails have a blue tinge
• Aches or pains in the body
• Bone pain
• Personality changes
• Urination burns
• Change in consciousness
• Color blindness with regard to yellow or blue
• Skin color at intravenous site changes
• Discomfort or pain in the chest area
• Urine appears cloudy
• Skin feels clammy or cold
• Congestion
• Hoarse voice, coughing with mucus or blood
• Crying for no reason
• Urination amount or frequency decreases
• Breathing is rapid or deep, leading to dizziness
• Delusions
• Depression
• Dementia
• Diarrhea
• Passing urine is difficult
• Breathing is difficult
• Moving is difficult
• Swallowing is difficult
• Veins in neck appear dilated
• Fainting, feeling dizzy or lightheaded
• Sleepy
• Sore throat or dry throat
• Dysphoria
• Pain in eyes
• Euphoria
• Unreal feeling
• Paranoia
• Hallucinations
• Chills
• Fever
• Dry skin that is flushed
• Urination is more frequent than normal
• Breath smells fruity
• Overall unwell feeling
• Wasting away physically
• Malnourishment
• More urination or more frequent urination
• Throbbing headache that is severe
• Welts or hives on skin
• Limbs seem paralyzed
• Restless, jittery
• Heart rhythm has increased
• Hunger is raging
• Skin is sensitive to sun
• Thirsty
• More urine than normal
• Urine appears diluted or pale
• Mouth waters
• Breathing is irregular
• Skin is sore, red, scaly, itchy or swollen
• Joints are painful
• Cramps in legs
• Little to no appetite
• No control over bladder function
• Passing out or losing consciousness
• Memory loss
• No strength or energy
• Pain in side or lower back
• Stiff, achy, painful muscles
• Jerking or twitching muscles
• Tender, weak muscles that feel wasted
• Vomiting
• Nausea
• Inability to keep still
• Pulse or blood pressure is undetectable
• Breathing has stopped
• Numb around mouth, hands or feet
• Numb, tingling lips, face, hands, arms or feet
• Tender, painful cheekbones or eye area
• Skin is pale
• Paralysis of half of the body
• Tiny red dots on skin
• Ears have pounding sensation
• Memory loss
• Over-emotional
• Breathing is too fast
• Heart rhythm is too rapid
• Gaining weight rapidly
• Moodiness
• Skin lesions or rashes
• Skin redness or other discolored patches or bumps
• Muscles move to an undetectable rhythm
• Seizures
• Other-worldly feeling
• Constipation
• Headache
• Mental changes or mood swings
• Severe chest pains
• Sunburn
• Uncontrollable vomiting
• Shivering
• Insomnia
• Lumps under skin
• Purple or red skin lesions
• Sneezing
• Ulcerated white spots on skin of lips or mouth
• Skin spots resembling blisters or acne
• Neck stiffness
• Heart stops
• Nasal congestion, stuffed up or running nose
• Severe and unexpected difficulty breathing
• Trouble breathing
• Eyes appear sunken
• Feet, fingers, face, lower legs or ankles are swollen
• Tongue swelling
• Joints are swollen
• Lymph glands in the armpit, groin or neck are swollen or painful
• Wheezing or chest tightness
• Difficulty breathing after exerting oneself
• Body twists
• Insomnia
• Losing consciousness
• Spastic, out of control movements of the neck, back or face
• Weight loss that is unexplained
• Behavior that is unusual
• Bruising or bleeding that is unexpected or unusual
• Feeling of weakness
• Changes in voice
• Vomiting coffee ground like matter
• Legs feel heavy
• Gaining weight
• Skin appears wrinkled

Other patients experience unwanted health effects that are temporary in nature and disappear as the medication is absorbed into your system. If you do have the following symptoms, pass them along to your physician in case there is a way to eliminate or ease them:

• Aural buzzing or ringing or other noises
• Sluggish response or awareness of surroundings
• Loss of hearing
• Extreme drowsiness
• Spastic movements of the eye
• Pain in the back
• Unpleasant taste in the mouth
• Vision changes or impairment
• Spinning or moving feeling
• Muscle weakness
• Pain in pelvic area
• Acid reflux
• Gas, belching, bloated feeling
• Pupils of the eye appear dilated or larger
• Stomach or chest has burning sensation
• Dry, burning, itchy eyes
• Colors appear different
• Constipation
• Loss of night vision
• Eyes water excessively
• Pain in ears
• Feel like defecating more often
• Full, bloated feeling
• Heartburn
• Aural response is heightened
• Eyes are sensitive
• Upset stomach
• Genital or vaginal itching
• Taste diminishes
• Painful sex
• Swelling in or near the eyes or eyelids
• Straining while defecating
• Tender stomach with upset
• Vaginal discharge that is white, with or without odor
• Sudden pleasant odors are detected for no reason
• Yeast infection, vaginal
• Loss of weight

Still other adverse health effects occur for some patients, so if your health changes in any way after being treated with Fosphenytoin, it is best to alert your physician to these changes to provide you with assistance, should it be required.

Dosage

This medication is administered only in a hospital setting by a trained doctor, surgeon or nurse. Your dosage has been determined based on your particular condition and needs as well as many other factors.

In general, an injected dosage of Fosphenytoin for a patient with epileptic seizures is from 15 to 20 milligrams Phenytoin equivalents per kilogram of body weight, not to exceed 150 milligrams per minute intravenously. This should be followed by maintenance doses, as required. Other drugs may also be given at this time depending on the need required by the patient's health.

Patients will be monitored continuously with regard to blood pressure levels, function of the respiratory system and electrocardiogram analysis.

Patients younger than 17 years old are typically given the same 15 to 20 milligrams Phenytoin equivalents per kilogram of body weight as adult patients, also not to exceed 150 milligrams per minute of intravenous administration.

Interactions

Hypersensitivity to other medications, certain foods, animals, artificial additives and dyes should be communicated to your health care provider to avoid any unwanted reactions to Fosphenytoin. Inform your health care provider if you are taking any other medications including those that are available over the counter, vitamin and herbal therapies or holistic remedies. As this drug will most likely be administered to you while you are hospitalized, make sure that your medical history is up to date on your latest drug treatments so that it can be referred to for possible interactions.

All drug therapies come with risk factors that will be explained to you by your physician. You will also be given a patient leaflet that you should read completely. Ask questions about any information contained in this leaflet that you don't understand.

Some medications are able to be used together without harm or reduced effectiveness of either drug. Combination therapies are a way to combat symptoms and make the patient more able to live a normal life. However, there are some drugs that should not be combined. The following medications should never be administered while you are being treated with Fosphenytoin:

• Amifampridine
• Artemether
• Amisulpride
• Bepridil
• Atazanavir
• Cisapride
• Boceprevir
• Daclatasvir
• Cobicistat
• Delamanid
• Dasabuvir
• Dronedarone
• Delavirdine
• Elvitegravir
• Elbasvir
• Isavuconazonium
• Grazoprevir
• Maraviroc
• Lurasidone
• Ombitasvir
• Mesoridazine
• Pimozide
• Paritaprevir
• Praziquantel
• Piperaquine
• Rilpivirine
• Ranolazine
• Sparfloxacin
• Ritonavir
• Terfenadine
• Telaprevir
• Ziprasidone
• Thioridazine

The following medications are known to have adverse reactions with Fosphenytoin but may be critical to your health care. Make sure your physician knows if you take any of the following substances so that dosage amounts can be appropriately altered for safety and effectiveness:

• Abiraterone
• Amiodarone
• Afatinib
• Apazone
• Anagrelide
• Apremilast
• Apixaban
• Aripiprazole
• Aprepitant
• Axitinib
• Arsenic Trioxide
• Bedaquiline
• Beclamide
• Bortezomib
• Blinatumomab
• Brexpiprazole
• Bosutinib
• Buserelin
• Bupropion
• Calcifediol
• Cabozantinib
• Cariprazine
• Carbamazepine
• Clarithromycin
• Ceritinib
• Cobimetinib
• Clozapine
• Cyclophosphamide
• Crizotinib
• Dabrafenib
• Dabigatran Etexilate
• Deferasirox
• Dasatinib
• Deslorelin
• Degarelix
• Diazoxide
• Diazepam
• Domperidone
• Dolutegravir
• Dopamine
• Donepezil
• Doxorubicin Hydrochloride Liposome
• Eliglustat
• Efavirenz
• Erlotinib
• Enzalutamide
• Eslicarbazepine Acetate
• Escitalopram
• Doxorubicin
• Etravirine
• Ethosuximide
• Exemestane
• Fentanyl
• Everolimus
• Ezogabine
• Fosaprepitant
• Fluoxetine
• Golimumab
• Fluvastatin
• Goserelin
• Gefitinib
• Histrelin
• Gonadorelin
• Hydroxychloroquine
• Halothane
• Ibrutinib
• Hydrocodone
• Ifosfamide
• Hydroxyzine
• Infliximab
• Idelalisib
• Irinotecan Liposome
• Imatinib
• Ivabradine
• Irinotecan
• Itraconazole
• Ixabepilone
• Ivacaftor
• Ketoconazole
• Ixazomib
• Ledipasvir
• Lapatinib
• Levofloxacin
• Leuprolide
• Linagliptin
• Lidocaine
• Macitentan
• Lopinavir
• Methotrexate
• Manidipine
• Miconazole
• Metronidazole
• Moxifloxacin
• Mifepristone
• Naloxegol
• Nafarelin
• Nifedipine
• Netupitant
• Nimodipine
• Nilotinib
• Olaparib
• Nintedanib
• Orlistat
• Ondansetron
• Oxycodone
• Osimertinib
• Panobinostat
• Palbociclib
• Pazopanib
• Pasireotide
• Pimavanserin
• Perampanel
• Pixantrone
• Pitolisant
• Posaconazole
• Ponatinib
• Regorafenib
• Quetiapine
• Rifampin
• Reserpine
• Roflumilast
• Rocuronium
• Romidepsin
• Rolapitant
• Secukinumab
• Saquinavir
• Sevoflurane
• Sertraline
• Sofosbuvir
• Simeprevir
• Sorafenib
• Sonidegib
• St John's Wort
• Sotalol
• Sunitinib
• Sulpiride
• Tamoxifen
• Tacrolimus
• Temsirolimus
• Tasimelteon
• Thiotepa
• Theophylline
• Tofacitinib
• Ticagrelor
• Trabectedin
• Tolvaptan
• Ulipristal
• Triptorelin
• Velpatasvir
• Vandetanib
• Venetoclax
• Vemurafenib
• Vincristine
• Vilazodone
• Vinflunine
• Vincristine Sulfate Liposome
• Voriconazole
• Vorapaxar
• Zuclopenthixol
• Vortioxetine

The following drugs, while they may increase unwanted health effects with use of Fosphenytoin, may be necessary to your health care as well. Let your physician know if you are taking:

• Acetazolamide
• Acetaminophen
• Amitriptyline
• Acyclovir
• Atorvastatin
• Amprenavir
• Bexarotene
• Betamethasone
• Busulfan
• Bleomycin
• Carboplatin
• Capecitabine
• Chloramphenicol
• Caspofungin
• Ciprofloxacin
• Cimetidine
• Clobazam
• Cisplatin
• Clopidogrel
• Clofazimine
• Cyclosporine
• Cortisone
• Dexamethasone
• Desogestrel
• Dienogest
• Dicumarol
• Diltiazem
• Digitoxin
• Disulfiram
• Disopyramide
• Doxifluridine
• Doxepin
• Estradiol Cypionate
• Drospirenone
• Ethinyl Estradiol
• Estradiol Valerate
• Etonogestrel
• Ethynodiol Diacetate
• Fluconazole
• Felbamate
• Fluorouracil
• Fludrocortisone
• Folic Acid
• Fluvoxamine
• Ginkgo
• Fosamprenavir
• Isoniazid
• Imipramine
• Levomethadyl
• Levodopa
• Levothyroxine
• Levonorgestrel
• Meperidine
• Medroxyprogesterone Acetate
• Methoxsalen
• Mestranol
• Midazolam
• Methsuximide
• Nelfinavir
• Nafimidone
• Nisoldipine
• Nilutamide
• Norethindrone
• Norelgestromin
• Norgestrel
• Norgestimate
• Oxcarbazepine
• Ospemifene
• Pancuronium
• Paclitaxel
• Phenprocoumon
• Paroxetine
• Prednisolone
• Piperine
• Progabide
• Prednisone
• Quinine
• Quinidine
• Rifapentine
• Remacemide
• Rufinamide
• Risperidone
• Shankhapulshpi
• Sabeluzole
• Sirolimus
• Simvastatin
• Sulfamethoxazole
• Sulfamethizole
• Sulthiame
• Sulfaphenazole
• Telithromycin
• Tegafur
• Tiagabine
• Tenidap
• Ticrynafen
• Ticlopidine
• Tizanidine
• Tirilazad
• Topiramate
• Tolbutamide
• Triamcinolone
• Trazodone
• Tubocurarine
• Trimethoprim
• Valproic Acid
• Valacyclovir
• Verapamil
• Vecuronium
• Viloxazine
• Vigabatrin

Consult with your physician on whether to eat prior or during your treatment with Fosphenytoin or whether certain foods should be eliminated from your diet altogether. You should also inform your doctor if you are a regular user of tobacco products or alcoholic beverages, as these could affect the way Fosphenytoin works for you. It is not advised that you consume anything ethanol based while taking Fosphenytoin.

Your full medical history should be communicated to your physician in case you have diseases that would be dangerously affected by chemotherapy treatment such as Fosphenytoin. Specifically, the following health conditions have been known to become worse or limit the effectiveness of this medication:

• Blood diseases
• Bone marrow diseases
• Diabetes
• Heart rate issues
• Cardiac failure
• Low blood pressure
• Lymph node problems
• Enzyme issues
• Heart blockage
• Slow heart rhythm
• Low blood albumin levels
• Disease of the kidneys
• Disease of the liver

Warnings

Your health condition will be closely monitored while you are being treated with Fosphenytoin to make sure it is controlling your condition and that you aren't suffering from any adverse health effects. Blood sample testing may be involved in this monitoring process.

Fosphenytoin has been known to pose a risk to unborn children and should not be used in women who are pregnant or who may become pregnant. An effective birth control method is advised for use in women being treated with this medication. If you become pregnant while being treated with Fosphenytoin, inform your health care provider as soon as possible.

Data from studies on women who are breastfeeding has not been provided with any level of confidence that determines a risk to children and infants as far as transmission of Fosphenytoin through breast milk. Use of this medication on women who are nursing should be determined with regard to their health needs and the health of their children.

No data has been provided from studies on pediatric or geriatric patients with regard to the effectiveness of Fosphenytoin or with regard to increased risks. It is believed to be appropriate for these age groups, with the caution that geriatric patients may have kidney, heart or liver problems that may create an increased risk for them.

Delavirdine, also marketed as Rescriptor, is a medication that should not be used with Fosphenytoin treatment as the effect on your condition that is expected of Delavirdine will not be met if taking Fosphenytoin.

Some patients become lightheaded, pass out or are dizzy and less alert than they normally are. For this reason, driving, operating heavy machinery or power tools should not be done while you are on this medication.

Do not discontinue using the medication you are prescribed post injected dose of Fosphenytoin as your seizure condition could return if you do.

Be alert for signs of Drug Reaction with Eosinophilia and Systemic Symptoms condition, or DRESS, with use of Fosphenytoin, which includes:

• Swollen lymph glands located in the groin, neck or armpit
• Bruising or bleeding that is unusual or unexpected
• Fever
• Skin rash
• Yellow skin or eyes

Alert your physician if you feel as if your skin is burning or if you have needles and pins sensations or itching and tingling after your injection. Symptoms including hives or rashes on the skin or other hypersensitivities should also be reported to your doctor immediately.

This medication puts patients at risk for a skin condition called PGS, which can potentially be serious. Also known as purple glove syndrome, PGS can be indicated by signs of discoloration, swelling or pain at the site of the injection of Fosphenytoin. Let your health care professional know if your injection site appears strange in any way.

Blood sugar levels can be affected by the use of Fosphenytoin and diabetic patients should especially be monitored for glucose levels. Your doctor will need to know if you are diabetic or pre-diabetic if you have been given an injection of Fosphenytoin.

Avoid consuming alcoholic beverages while you are being treated with Fosphenytoin. Seek assistance if you require it during this time.

Your birth control pills may not be effective if you have been treated with Fosphenytoin injection, so use alternate forms of birth control while you are being administered this drug. Discuss your birth control options with your health care provider.

Many medications, vitamins and mineral supplements interact adversely with Fosphenytoin. Avoid taking any other medications while you are being treated with this drug, including over-the-counter, herbal, and holistic or vitamin supplements.

Storage

Fosphenytoin will be stored and administered in a hospital or medical clinic setting only, with storage according to the manufacturer's instructions carried out by the professional staff.

The manufacturer recommends that the vials of medication be stored in their original packaging under refrigerated conditions. While Fosphenytoin can be stored at room temperature, it should be discarded after 48 hours. Any opened Fosphenytoin should be used immediately or discarded according to safety instructions and local guidelines.

Summary

Fosphenytoin is a prodrug that isn't active until it is injected into the body, when it changes into Phenytoin, a powerful anti-seizure medication used to prevent and treat convulsions and seizures that may result when a patient has neurosurgery as well as those experienced by patients with epilepsy. Proven to be safer than an administration of Phenytoin itself, it provides better tolerance at the injection site and has less of a risk of causing cardiac and blood pressure issues. The cost of Fosphenytoin, however, is higher than that of Phenytoin, so it is typically administered to patients who cannot tolerate intravenous route drugs or those who could not withstand PGS, if infected.

By blocking certain channels in the motor cortex region of the brain, which is the central portion, Fosphenytoin effectively calms hyperactive electrical activity generated in the brain of patients who are epileptic. Fosphenytoin calms this activity and halts the seizure.

This medication is only for temporary administration via injection and should not be used for longer than 5 days to control the seizure condition. After this, the patient will be prescribed oral medication to take control of their seizures. Dosage amount, storage safety and other considerations are the responsibility of professional medical staff located at the hospital or clinic where Fosphenytoin is administered.

Unwanted health effects may include confusion, drowsiness, nervous demeanor, nausea, constipation, skin symptoms, uncontrolled body, eye or facial movements, headaches and insomnia or upset stomach. Serious, severe or prolonged symptoms should be reported to your physician immediately. Fosphenytoin poses a risk of PGS, an infection of the injection site as well as liver damage and DRESS syndrome. Changes to your overall health or wellbeing should be communicated to your health care professional immediately to avoid long-term health damage.

Patients are instructed not to consume alcoholic beverages while being treated with Fosphenytoin. Patients should also avoid taking any other medications with this drug, whether they are prescription or non-prescription, as the list of interactivity that causes adverse health effects is extensive. Patients may be at risk of heart failure if this drug is administered too quickly. Patients are also at risk if they have liver or kidney diseases or if they are diabetic. Make sure your full medical history is available to your doctor should you require treatment with Fosphenytoin.

Most patients are able to benefit from the effects of Fosphenytoin, should they need emergency brain seizure treatment. Women who are pregnant or who are nursing should avoid this treatment unless it is an emergency, as it can pose a risk to their unborn children or infants. Geriatric patients who have kidney, liver or cardiac diseases should also be administered Fosphenytoin with caution.